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Stress is widely recognized as the primary environmental factor associated with chronic pain conditions, including fibromyalgia. A recent study demonstrated the potential antinociceptive effects of 4-amino-3-(phenylselanyl) benzenesulfonamide (4-APSB) in acute nociceptive animal models due to its antioxidant and anti-inflammatory properties. However, the efficacy of 4-APSB in managing chronic painful conditions, such as fibromyalgia, has not been explored so far. This study investigated the pharmacological effects of 4-APSB in an experimental model of fibromyalgia induced by intermittent cold stress (ICS). Male and female mice were divided into Control, ICS, 4-APSB, and ICS + 4-APSB. After the ICS, the animals were treated with 4-APSB (1 mg kg -1 ) or vehicle by the intragastric route until the tenth day. The behavioral tasks were performed on days 5, 8, and 10. The findings showed a negative correlation between paw withdrawal threshold and Nrf2 or NFκB mRNA expression levels caused by ICS exposure. The 4-APSB suppressed the nociceptive signs and a depressive like-phenotype in male and female mice exposed to ICS. 4-APBS normalized the elevated levels of TBARS and the up-regulation of Nrf2 and NFκB expression in the cerebral cortex of ICS-exposed mice. This compound also modulated the oxidative stress in the spinal cord of female mice. The 4-APSB attenuated the inhibition of Na + , K + - ATPase activity in the central nervous system (CNS) of female mice exposed to ICS. 4-APSB attenuated behavioral and redox imbalance triggered by the ICS model in male and female mice, suggesting its beneficial effects for treating fibromyalgia in both sexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

This study aimed to elucidate vincristine (VCR)-induced peripheral neuropathy in aged rats, a poorly understood neurotoxicity. Both young and old Wistar rats were administered VCR (0.1 mg/kg, intraperitoneally (i.p.)) and compared to age-matched controls (0.9% saline; 10 mg/mL, i.p.). Mechanical (MN) and thermal nociceptive (TN) responses were assessed on days 0, 6, 11, and 17. Locomotor response, cognitive ability, and anxious-like behavior were evaluated on days 14, 15, and 16. Results showed MN and TN responses in both young and old VCR-exposed rats. In old rats, VCR exacerbated MN (on days 6, 11, and 17) and TN (on days 6 and 17) responses. VCR also induced cognitive impairments and anxiety-like behavior. Histological analysis revealed Wallerian degeneration in the spinal cords of VCR-exposed rats accompanied by macrophage migration. Furthermore, VCR increased Ca 2+ -ATPase activity while inhibiting Na + , K + -ATPase activity in young and old rats. VCR altered the homeostasis of Mg 2+ -ATPase activity. Lipid peroxidation and nitrite and nitrate levels increased in young and old rats exposed to VCR. This study provides valuable insights into VCR's mechanistic pathways in aged rats, emphasizing the need for further research in this area.

Rationale: The compound 5-((4-methoxyphenyl)thio)benzo[c][1,2,5]thiadiazole (MTDZ) has recently been shown to inhibit in vitro acetylcholinesterase activity, reduce cognitive damage, and improve neuropsychic behavior in mice, making it a promising molecule to treat depression., Objectives: This study investigated the antidepressant-like action of MTDZ in mice and its potential mechanisms of action., Results: Molecular docking assays were performed and suggested a potential inhibition of monoamine oxidase A (MAO-A) by MTDZ. The toxicity study revealed that MTDZ displayed no signs of toxicity, changes in oxidative parameters, or alterations to biochemistry markers, even at a high dose of 300 mg/kg. In behavioral tests, MTDZ administration reduced immobility behavior during the forced swim test (FST) without adjusting the climbing parameter, suggesting it has an antidepressant effect. The antidepressant-like action of MTDZ was negated with the administration of 5-HT1A, 5-HT1A/1B, and 5-HT3 receptor antagonists, implying the involvement of serotonergic pathways. Moreover, the antidepressant-like action of MTDZ was linked to the NO system, as L-arginine pretreatment inhibited its activity. The ex vivo assays indicated that MTDZ normalized ATPase activity, potentially linking this behavior to its antidepressant-like action. MTDZ treatment restricted MAO-A activity in the cerebral cortices and hippocampi of mice, proposing a selective inhibition of MAO-A associated with the antidepressant-like effect of the compound., Conclusions: These findings suggest that MTDZ may serve as a promising antidepressant agent due to its selective inhibition of MAO-A and the involvement of serotonergic and NO pathways., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) shows promise for its antinociceptive and anti-inflammatory properties. Here, we explored the structure-activity relationship of 4-PSQ and its analogues: 7-chloro-4-[(4-fluorophenyl) selanyl]quinoline (a), 7-chloro-4-{[3-trifluoromethyl)phenyl] selanyl} quinoline (b), 4-((3,5-Bis(trifluoromethyl)phenyl) selanyl-7-chloroquinoline (c), 7-chloro-4-[(2,4,6-trimethyl)selanyl]quinolinic acid (d) and 7-chloroquinoline-4-selenium acid (e) in models of acute inflammation and chemical, thermal and mechanical nociception in mice, alongside in silico analysis. Compounds a (-F), b (-CF 3 ), c (-Bis-CF 3 ), d (-CH 3 ), e (-OOH), and 4-PSQ exhibited antinociceptive effects in chemical and thermal nociception models, except d (-CH 3 ) and e (-OOH) in the hot plate test. None induced locomotor changes. In silico, only c (-Bis-CF 3 ) showed low gastrointestinal absorption, and c (-Bis-CF 3 ) and e (-OOH) lacked blood-brain barrier penetration, suggesting e (-OOH) lacked central antinociceptive effect. These compounds had higher COX-2 affinity than COX-1. Our findings suggest substituent insertion alters 4-PSQ's efficacy as an antinociceptive and anti-inflammatory agent., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Numerous factors can contribute to the incidence or exacerbation of peripheral neuropathy induced by oxaliplatin (OXA). Recently, platinum accumulation in the spinal cord of mice after OXA exposure, despite the efficient defenses of the central nervous system, has been demonstrated by our research group, expanding the knowledge about its toxicity. One hypothesis is platinum accumulation in the spinal cord causes oxidative damage to neurons and impairs mitochondrial function. Thus, the main aim of this study was to investigate the relationship between aging and OXA-induced neuropathic pain and its comorbidities, including anxious behavior and cognitive impairment. By using an OXA-induced peripheral neuropathy model, platinum and bioelement concentrations and their influence on oxidative damage, neuroprotection, and neuroplasticity pathways were evaluated in Swiss mice, and our findings showed that treatment with OXA exacerbated pain and anxious behavior, albeit not age-induced cognitive impairment. Platinum deposition in the spinal cord and, for the first time, in the brain of mice exposed to OXA, regardless of age, was identified. We found that alterations in bioelement concentration, oxidative damage, neuroprotection, and neuroplasticity pathways induced by aging contribute to OXA-induced peripheral neuropathy. Our results strive to supply a basis for therapeutic interventions for OXA-induced peripheral neuropathy considering age specificities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sleep is a fundamental state for maintaining the organism homeostasis. Disruptions in sleep patterns predispose to the appearance of memory impairments and mental disorders, including depression. Recent pre-clinical studies have highlighted the antidepressant-like properties of the synthetic compound 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1). To further investigate the neuromodulatory effects of SeBZF1, this study aimed to assess its therapeutic efficacy in ameliorating neurobehavioral impairments induced by sleep deprivation (SD) in mice. For this purpose, a method known as multiple platforms over water was used to induce rapid eye movement (REM) SD. Two hours after acute SD (24 h), male Swiss mice received a single treatment of SeBZF1 (5 mg/kg, intragastric route) or fluoxetine (a positive control, 20 mg/kg, intraperitoneal route). Subsequently, behavioral tests were conducted to assess spontaneous motor function (open-field test), depressive-like behavior (tail suspension test), and memory deficits (Y-maze test). Brain structures were utilized to evaluate oxidative stress markers, monoamine oxidase (MAO) and acetylcholinesterase (AChE) activities. Our findings revealed that SD animals displayed depressive-like behavior and memory impairments, which were reverted by SeBZF1 and fluoxetine treatments. SeBZF1 also reverted the increase in lipoperoxidation levels and glutathione peroxidase activity in the pre-frontal cortex in mice exposed to SD. Besides, the increase in hippocampal AChE activity induced by SD was overturned by SeBZF1. Lastly, cortical MAO-B activity was reestablished by SeBZF1 in mice that underwent SD. Based on the main findings of this study, it can be inferred that the compound SeBZF1 reverses the neurobehavioral alterations induced by sleep deprivation in male Swiss mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients' quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa β. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation.

The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclitaxel (PTX)-induced peripheral neuropathy was investigated in male and female Swiss mice. The study examined the effects of MTDZ on various pathways, including transient receptor potential cation channel subfamily V member 1 (TRPV1), glutamatergic, nitrergic, guanylate cyclase (cGMP), serotonergic, and opioidergic. Mice received intraperitoneal PTX (2 mg/kg) or vehicle on days 1, 2, and 3, followed by oral MTDZ (1 mg/kg) or vehicle from days 3 to 14. Mechanical and thermal sensitivities were assessed using Von Frey and hot plate tests on days 8, 11, and 14. The open field test evaluated locomotion and exploration on day 12. On day 15, nitrite and nitrate (NOx) levels and Ca 2+ -ATPase activity in the cerebral cortex and spinal cord were measured after euthanizing the animals. MTDZ administration reversed the heightened mechanical and thermal sensitivities induced by PTX in male and female mice without affecting locomotion or exploration. MTDZ also modulated multiple pathways, including glutamatergic, NO/L-arginine/cGMP, serotonergic (5-HT 1A/1B ), opioid, and TRPV1 pathways. Additionally, MTDZ reduced NOx levels and modulated Ca 2+ -ATPase activity. In conclusion, MTDZ effectively alleviated PTX-induced peripheral neuropathy and demonstrated multi-targeted modulation of pain-related pathways. Its ability to modulate multiple pathways, reduce NOx levels, and modulate Ca 2+ -ATPase activity makes it a potential pharmacological candidate for peripheral neuropathy, acute nociceptive, and inflammatory conditions. Further research is needed to explore its therapeutic potential in these areas.

New compounds and pharmacological strategies offer alternatives for treating chronic skin diseases, such as atopic dermatitis (AD). Here, we investigated the incorporation of 1,4-anhydro-4-seleno-d-talitol (SeTal), a bioactive seleno-organic compound, in gelatin and alginate (Gel-Alg) polymeric films as a strategy for improving the treatment and attenuation of AD-like symptoms in a mice model. Hydrocortisone (HC) or vitamin C (VitC) were incorporated with SeTal in the Gel-Alg films, and their synergy was investigated. All the prepared film samples were able to retain and release SeTal in a controlled manner. In addition, appreciable film handling facilitates SeTal administration. A series of in-vivo/ex-vivo experiments were performed using mice sensitized with dinitrochlorobenzene (DNCB), which induces AD-like symptoms. Long-term topical application of the loaded Gel-Alg films attenuated disease symptoms and pruritus, with suppression of the levels of inflammatory markers, oxidative damage, and the skin lesions associated with AD. Moreover, the loaded films showed superior efficiency in attenuating the analyzed symptoms when compared to hydrocortisone (HC) cream, a traditional AD-treatment, and decreased the inherent drawbacks of this compound. In short, incorporating SeTal (by itself or with HC or VitC) in biopolymeric films provides a promising alternative for the long-term treatment of AD-type skin diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: [The authors declare that they have no conflicts of interest, except for M.J.D. and C.H.S. who are major shareholders and Directors of Seleno Therapeutics Pty. Ltd., which holds patents on the development and use of SeTal]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most common form of dementia in older people, and available treatments are palliative and produce undesirable side effects. The 4-phenyltellanyl-7-chloroquinoline (TQ) is an organochalcogen compound studied due to its pharmacological properties, particularly its antioxidant potential. However, TQ possesses some drawbacks such as low aqueous solubility and high toxicity, thus warranting the search for tools that improve the safety and effectiveness of new compounds. Here, we developed and investigated the biological effects of TQ-loaded polymeric nanocapsules (NCTQ) in an AD model in transgenic Caenorhabditis elegans expressing human Aβ 1-42 in their body-wall muscles and Swiss mice injected with Aβ 25-35 . The NCTQ displayed good physicochemical properties, including nanometer size and maximum encapsulation capacity. The treatment showed low toxicity, reduced Aβ peptide-induced paralysis, and activated an endoplasmic reticulum chaperone in the C. elegans model. The Aβ injection in mice caused memory impairment, which NCTQ mitigated by improving working, long-term, and aversive memory. Additionally, no changes in biochemical markers were evidenced in mice, demonstrating that there was no hepatotoxicity in the tested doses. Altogether, these findings provide insights into the neuroprotective effects of TQ and indicate that NCTQ is a promising candidate for AD treatment.

In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (Aβ) (25-35 fragment), 3 nmol/3 μl/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). Aβ caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-κB (NF-κB), and the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in cerebral cortex and hippocampus. Additionally, Aβ increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-κB in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by Aβ. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cu(II) complexes bearing NNO-donor Schiff base ligands ( 2a , b ) have been synthesized and characterized. The single crystal X-ray analysis of the 2a complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations. The monomeric nature of 2a and 2b species is maintained in solution. Antioxidant activities of the ligands ( 1a , b ) and Cu(II) complexes ( 2a , b ) were determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH . ) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS + ). Our results demonstrated that 2a showed better antioxidant activity. MTT assays were performed to assess the toxicity of ligands and Cu(II) complexes in V79 cells. The antiproliferative activity of compounds was tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and SW620 (colorectal carcinoma) and on MRC-5 (normal lung fibroblast). All compounds showed high cytotoxicity in the all-cell lines but showed no selectivity for tumor cell lines. Antiproliferative activity by clonogenic assay 2b showed a more significant inhibitory effect on the MCF-7 cell lines than on MRC-5. DNA damage for the 2b compound at 10 µM concentration was about three times higher in MCF-7 cells than in MRC-5 cells.

In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules was developed for topical treatment of atopic dermatitis (AD). The bilayer films were produced by applying a pullulan layer on a gellan gum layer incorporated with silibinin nanocapsules by two-step solvent casting method. The bilayer formation was confirmed by microscopic analysis. In vitro studies showed that pullulan imparts bioadhesitvity for the films and the presence of nanocapsules increased their occlusion factor almost 2-fold. Besides, the nano-based film presented a slow silibinin release and high affinity for cutaneous tissue. Moreover, this film presented high scavenger capacity and non-hemolytic property. In the in vivo study, interestingly, the treatments with vehicle film attenuated the scratching behavior and the ear edema in mice induced by 2,4-dinitrochlorobenzene (DNCB). However, the nano-based film containing silibinin modulated the inflammatory and oxidative parameters in a similar or more pronounced way than silibinin solution and vehicle film, as well as than hydrocortisone, a classical treatment of AD. In conclusion, these data suggest that itself gellan gum/pullulan bilayer film might attenuate the effects induced by DNCB, acting together with silibinin-loaded nanocapsules, which protected the skin from oxidative damage, improving the therapeutic effect in this AD-model.

Paclitaxel-induced peripheral neuropathy (PIPN) is a very common and complex painful condition related to paclitaxel (PTX) exposure, severely impacting patients' quality of life, and contributing to the emergence of clinical signs of anxiety and cognitive loss. At present, no sufficient treatment options are available for PIPN and its exact pathophysiology remains unclear. Based on the therapeutic potential of the 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), we assessed its ability to reverse PIPN and its comorbities induced by PTX. The effect of 4-PSQ was evaluated on pathophysiological processes involved in PIPN, such as oxidative stress (oxidative damage and antioxidant enzymes), neuroinflammation (mRNA expression levels of nuclear factor-kappa B, interleukin-1beta, tumor necrosis factor-alpha, and inducible nitric oxide synthase), and calcium homeostasis (Ca 2+ ATPase activity) in the spinal cord, cerebral cortex, and hippocampus of mice. Male Swiss mice received PTX (2 mg/kg) or vehicle by intraperitoneal route (days 1, 2, and 3). Oral administration of 4-PSQ (1 mg/kg) or vehicle was performed on days 3 to 14. It was observed that 4-PSQ reduced the mechanical and thermal hypersensitivities induced by PTX. Likewise, 4-PSQ reduced both anxious behavior and cognitive impairment in mice with PIPN. We believe that effects of 4-PSQ may be associated, at least in part, with the modulation of oxidative stress, reduction of neuroinflammation, and normalizing Ca 2+ ATPase activity in the spinal cord, cerebral cortex, and hippocampus of mice with PIPN. Taken together, the 4-PSQ might be a good prototype for the development of a more effective drug for the treatment of PIPN and its comorbities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fibromyalgia results from a complex interplay of biochemical and neurobiological elements mediated sensitization of nociceptive pathways. Despite the symptoms of fibromyalgia negatively affect the quality of life of patients, the pathophysiology of this disease remains inconclusive, which difficult the development of an appropriate treatment. The present study investigated the involvement of the serotonergic receptors, the N-methyl-D-aspartate (NMDA)/ nitric oxide (NO)/ cyclic guanosine monophosphate (cGMP) pathway and the oxidative stress in an animal model of fibromyalgia induced by intermittent cold stress (ICS), considering the specificities of male and female Swiss mice. The ICS exposure increased mechanical and thermal sensitivities, and decreased muscle strength in mice of both sexes. Female mice exhibited a longer-lasting mechanical sensitivity than male mice exposed to ICS along with an enhancement of the Na + , K + -ATPase activity in the spinal cord and cerebral cortex. Conversely, an inhibition in the Na + , K + -ATPase and glutathione peroxidase activities accompanied by an increase in the reactive species levels in the cerebral cortex of male mice were observed. The treatment with different serotonergic antagonists (pindolol, ketanserin and ondasetron) reversed the mechanical sensitivity in mice of both sexes, after the ICS exposure. The administration of MK-801, L-arginine and methylene blue also blocked the mechanical sensitivity in female mice exposed to ICS. Except L-arginine, MK-801 and methylene blue also attenuated this nociceptive signal in male mice, after ICS exposure. In conclusion, the modulation of serotonergic receptors, the NMDA/NO/cGMP pathway, and the oxidative stress seems contribute to nociceptive behaviors induced by ICS exposure sex-dependent., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present study evaluated the protective effect of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) on seizure severity, oxidative stress, and memory disorder in a pentylenetetrazole (PTZ)-kindling model in mice. Male Swiss mice were treated with QTCA-1 (10 mg/kg, intragastrically (i.g.)) or phenobarbital (PHEN) (10 mg/kg; i.g.), 30 min before the injection of PTZ (35 mg/kg, intraperitoneally (i.p.)). Treatments with QCTA-1 or PHEN and PTZ were performed once every 48 h (on the 1st, 3rd, 5th, 7th, 9th and 11th days). After each PTZ injection, the animals were observed for 30 min to assess the stage of seizure intensity. Behavioral parameters were evaluated from the 12th day until the 16th day of the experimental protocol. On the 16th day, mice were euthanized, and the cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) and reactive species (RS) levels, and superoxide dismutase (SOD), Na + /K + -ATPase and acetylcholinesterase (AChE) activities. Our results demonstrated that QTCA-1 significantly decreased the seizure stage score in PTZ-kindled mice. QCTA-1 protected against memory impairment induced by PTZ. QTCA-1 normalized oxidative stress and Na + /K + -ATPase activity in the cerebral structures of PTZ-kindled mice. The effect of QTCA-1 treatment was similar to the positive control used in this study (PHEN). AChE activity did not change in the cerebral structures in PTZ- kindling mice. In conclusion, QCTA-1 may be a promising tool for the treatment of epileptogenesis and epilepsy-associated comorbidity (memory impairment). QCTA-1 to prevent these alterations may involve the reduction of oxidative stress and normalization of Na + /K + -ATPase activity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Almost 90% of patients develop pain immediately after oxaliplatin (OXA) treatment. Here, the impact of aging on OXA-induced acute peripheral neuropathy and the potential of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) as a new therapeutic strategy were evaluated. In Swiss mice, the oxidative damage and its influence on Mg 2+ -ATPase and Na + , K + -ATPase activities were investigated. The relationship between the reactive oxygen species (ROS) and nitrate and nitrite (NOx) levels, the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD) with the development of OXA-induced acute peripheral neuropathy was also studied. In this study, it was evidenced that OXA-induced acute peripheral neuropathy was exacerbated by aging through increased oxidative damage as well as Na + , K + -ATPase, and Mg +2 -ATPase inhibition. 4-PSQ reversed hypersensitivity induced by OXA and aging-aggravated by reducing ROS and NOx levels, through modulation of GPx and SOD activities. 4-PSQ partially reestablish Na + , K + -ATPase activity, but not Mg 2+ -ATPase activity. Locomotor and exploratory activities were not affected. This study is the first of its kind, providing new insight into the aging impact on mechanisms involved in OXA-induced acute peripheral neuropathy. Also, it provides evidence on promising 4-PSQ effects on this condition, mainly on aging., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Herein we describe results for the synthesis and synthetic application of 4-amino-3-(arylselenyl)benzenesulfonamides, and preliminary evaluation of antioxidant, anti-edematogenic and antinociceptive properties. This class of compounds was synthesized in good yields by a reaction of commercially available sulfanilamide and diorganyl diselenides in the presence of 10 mol% of I 2 . Furthermore, the synthesized compound 4-amino-3-(phenylselenyl)benzenesulfonamide (3 a) was evaluated on complete Freund's adjuvant (CFA)-induced acute inflammatory pain. Dose- and time-response curves of antinociceptive effect of compound 3 a were performed using this experimental model. Also, the effect of compound 3 a was monitored in a hot-plate test to evaluate the acute non-inflammatory antinociception. The open-field test was performed to evaluate the locomotor and exploratory behaviors of mice. Oxidative stress markers, such as glutathione peroxidase activity; reactive species, non-protein thiols, and lipid peroxidation levels were performed to investigate the antioxidant action of compound 3 a. Our findings suggest that the antioxidant effect of compound 3 a may contribute to reducing the nociception and suppress the signaling pathways of inflammation on the local injury induced by CFA. Thus, compound 3 a reduced the paw edema as well as the hyperalgesic behavior in mice, being a promising therapeutic agent for the treatment of painful conditions., (© 2021 Wiley-VCH GmbH.)

In the present study it was hypothesized that 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ), a new acetylcholinesterase inhibitor, exerts antinociceptive action and reduces the oxaliplatin (OXA)-induced peripheral neuropathy and its comorbidities (anxiety and cognitive deficits). Indeed, the acute antinociceptive activity of MTDZ (1 and 10 mg/kg; per oral route) was observed for the first time in male Swiss mice in formalin and hot plate tests and on mechanical withdrawal threshold induced by Complete Freund's Adjuvant (CFA). To evaluate the MTDZ effect on OXA-induced peripheral neuropathy and its comorbidities, male and female Swiss mice received OXA (10 mg/kg) or vehicle intraperitoneally, on days 0 and 2 of the experimental protocol. Oral administration of MTDZ (1 mg/kg) or vehicle was performed on days 2-14. OXA caused cognitive impairment, anxious-like behaviour, mechanical and thermal hypersensitivity in animals, with females more susceptible to thermal sensitivity. MTDZ reversed the hypersensitivity, cognitive impairment and anxious-like behaviour induced by OXA. Here, the negative correlation between the paw withdrawal threshold caused by OXA and acetylcholinesterase (AChE) activity was demonstrated in the cortex, hippocampus, and spinal cord. OXA inhibited the activity of total ATPase, Na + K + - ATPase, Ca 2+ - ATPase and altered Mg 2+ - ATPase in the cortex, hippocampus, and spinal cord. OXA exposure increased reactive species (RS) levels and superoxide dismutase (SOD) activity in the cortex, hippocampus, and spinal cord. MTDZ modulated ion pumps and reduced the oxidative stress induced by OXA. In conclusion, MTDZ is an antinociceptive molecule promising to treat OXA-induced neurotoxicity since it reduced nociceptive and anxious-like behaviours, and cognitive deficit in male and female mice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Methotrexate (MTX) is a common drug used for rheumatoid arthritis (RA) treatment; however, a series of adverse effects associated with its oral or subcutaneous administration is reported. Transdermal delivery of MTX is an alternative to abate these issues, and the use of drug delivery systems (DDS) based on polymeric films presents an impressive potential for this finality. Based on this, in this study, we report the preparation of films made by cationic starch (CSt), poly(vinyl alcohol) (PVA), and chondroitin sulfate (ChS) to incorporate and release MTX, as well as the in vivo evaluation in model of rheumatoid arthritis in mice. CSt/PVA and CSt/PVA/ChS-based films (with and without MTX) were prepared using a simple protocol under mild conditions. The films loaded with 5 w/w-% of MTX exhibited appreciable drug loading efficiency and distribution. The MTX permeation through the layers of porcine skin demonstrated that most of the drug permeated was detected in the medium, suggesting that the formulation can provide a systemic absorption of the MTX. In vivo studies performed in an arthritis-induced model in mice demonstrated that the MTX-loaded films were able to treat and attenuate the symptoms and the biochemical alterations related to RA (inflammatory process, oxidative stress, and nociceptive behaviors). Besides, the pharmacological activity of MTX transdermally delivery by the CSt/PVA and CSt/PVA/ChS films was comparable to the MTX orally administered. Based on these results, it can be inferred that both films are prominent materials for incorporation and transdermal delivery of MTX in a practical and non-invasive manner., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aim of the present study was investigate the binding affinity of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5]thiadiazole (MTDZ) with acetylcholinesterase (AChE). We also evaluated the effect of MTDZ against scopolamine (SCO)-induced amnesia in mice and we looked at the toxicological potential of this compound in mice. The binding affinity of MTDZ with AChE was investigated by molecular docking analyses. For an experimental model, male Swiss mice were treated daily with MTDZ (10 mg/kg, intragastrically (i.g.)) or canola oil (10 ml/kg, i.g.), and induced, 30 min later, with injection of SCO (0.4 mg/kg, intraperitoneally (i.p.)) or saline (0.9%, 5 ml/kg, i.p.) daily. From day 1 to day 10, mice were submitted to the behavioral tasks (Barnes maze, open-field, object recognition and location, Y-maze and step-down inhibitory avoidance tasks), 30 min after induction with SCO. On the tenth day, the animals were euthanized and blood was collected for the analysis of biochemical markers (creatinine, aspartate (AST), and alanine (ALT) aminotransferase). MTDZ interacts with residues of the AChE active site. SCO caused amnesia in mice by changing behavioral tasks. MTDZ treatment attenuated the behavioral changes caused by SCO. In ex vivo assay, MTDZ also protected against the alteration of AChE activity, reactive species (RS) levels, thiobarbituric acid reative species (TBARS) levels, catalase (CAT) activity in tissues, as well as in transaminase activities of plasma caused by SCO in mice. In conclusion, MTDZ presented anti-amnesic action through modulation of the cholinergic system and provided protection from kidney and liver damage caused by SCO., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: Depression is often associated with memory impairment, a clinical feature of Alzheimer's disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system., Objectives: The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated., Methods: ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1β, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus., Results: 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation., Conclusions: These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The derivatization of chitosan (CS) is widely exploited to endow this polysaccharide with enhanced physicochemical and biological properties. Beyond the synthetic route, the nature of the compounds used to functionalize the CS-derivatives exerts a pivotal role in their final properties. Making use of a simple "click" reaction, we synthesized for the first time an organoselenium-CS derivative through a 1,2,3-triazole formation. The product (CS-TSe) was characterized in detail by FTIR, NMR ( 1 H, 13 C, and 77 Se) and UV-Vis techniques, and SEM microscopy. The antioxidant activity of CS-TSe was examined by ABTS + and DPPH (free radical-scavenging) assays. Experimentally, it was demonstrated that CS-TSe has superior antioxidant activity compared with raw CS and "free" organoselenium compound, suggesting a benign and synergistic effect due to the derivatization. In short, the antioxidant property of CS-TSe combined with the other attractive properties of CS and selenium could be useful in the formulation of advanced materials for biomedical and packaging applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite major advances, not all patients achieve rheumatoid arthritis (RA) remission, thus highlighting a pressing need for new therapeutic treatments. Given this scenario, this study sought to evaluate Se-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl] 4-chlorobenzoselenolate (Se-DMC) potential on a complete Freund's adjuvant (CFA)-induced unilateral arthritis model. The effects of Se-DMC (5 mg/kg; oral dose) and meloxicam (5 mg/kg; oral dose), both administered to animals daily for 14 days, on paw edema, mechanical sensitivity, neurobehavioral deficits (anxiogenic- and depressive-like behaviors), Na + /K + -ATPase activity, oxidative stress, and inflammation were evaluated in male Swiss mice exposed to CFA (intraplantar injection of 0.1 mL; 10 mg/mL). Se-DMC reduced the paw withdrawal threshold and CFA-induced paw edema. Histopathological results revealed the antiedematogenic potential of the compound, which was evidenced by lower quantities of dilated lymphatic vessels compared with the CFA group. Se-DMC reduced mRNA relative expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the hippocampus and paw of CFA mice. The CFA-induced anxiogenic- and depressive-like behaviors were reversed by Se-DMC to the control levels in the elevated plus-maze and tail suspension tests. Se-DMC reduced the paw reactive species levels and restored the superoxide dismutase (hippocampus and paw) and Na + /K + -ATPase (hippocampus) activities previously increased by CFA. Moreover, CFA administration inhibited serum creatinine kinase activity, albeit the Se-DMC effects did not appear to involve the modulation of this enzyme and were equal to or greater than meloxicam. Se-DMC attenuates CFA-induced inflammatory response, nociception, and neurobehavioral deficits in mice.

The object of this study was to evaluate the relationship between oxidative damage induced by oxaliplatin (OXA) and the therapeutic potential of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) in kidney of mice. Mice received OXA (10 mg/kg) or vehicle intraperitoneally (days 0 and 2). Oral administration of 4-PSQ (1 mg/kg) or vehicle was performed on days 2 to 14. On day 15 the animals were euthanized and the kidneys and blood were collected. The effect of OXA and (or) 4-PSQ on urea, thiobarbituric acid reactive species, nonprotein thiol (NPSH), and protein carbonyl (PC) levels were investigated. Moreover, renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), δ-aminolevulinic acid dehydratase (δ-ALA-D), and Na + ,K + ATPase activities were evaluated. Our findings revealed an increase on urea levels and significant renal oxidative damage in OXA-induced mice. OXA exposure increased SOD, GPx, and GST activities and caused a reduction on NPSH levels and CAT and GR activities. Na + ,K + ATPase and δ-ALA-D activities were reduced by OXA. 4-PSQ decreased plasmatic urea levels and renal oxidative damage. SOD, GPx, CAT, GR, and Na + ,K + ATPase activities were restored by 4-PSQ. 4-PSQ may be a good prototype for the treatment of OXA-induced renal injury.

Background: Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease that affects ∼20 % of children and 3% of adults globally and is generally treated by the topical application of steroidal drugs that have undesirable side-effects. The development of alternative therapies is therefore an important objective. The present study investigated the effects of topical treatment with a novel water-soluble selenium-containing carbohydrate derivative (4-anhydro-4-seleno-D-tatitol, SeTal) on the symptoms and inflammatory parameters in an AD mouse model., Methods: Mice were sensitized by applying 2,4-dinitrochlorobenzene (DNCB) to their dorsal skin on days 1-3, then further challenged on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. SeTal (1 and 2%) or hydrocortisone (1%) was applied topically to the backs of the mice from days 14-29, and skin severity scores and scratching behavior determined on day 30. The mice were euthanized, and their ears and dorsal skin removed to quantify inflammatory parameters, edema, myeloperoxidase (MPO) activity, and AD-associated cytokines (tumor necrosis factor alpha (TNF-α), interleukins (IL)-18, and IL-33)., Results: DNCB treatment induced skin lesions and increased the scratching behavior, ear edema, MPO activity (ear and dorsal skin), and cytokine levels in dorsal skin. Topical application of SeTal improved inflammatory markers (cytokine levels and MPO activity), cutaneous severity scores, and scratching behavior., Conclusion: The efficacy of SeTal was satisfactory in the analyzed parameters, showing similar or better results than hydrocortisone. SeTal appears to be therapeutically advantageous for the treatment and control of AD., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Aims: Obesity is associated with a spectrum of hepatic abnormalities that can be experimentally induced by injections of monosodium glutamate (MSG) in neonatal rodents. We investigated the protective actions of the repeated therapy with 4-phenylselenyl-7-chloroquinoline (4-PSQ), a quinoline derivative containing selenium, on damage to the liver triggered by early postnatal administration of MSG in male Wistar rats., Main Methods: Neonatal rats received MSG (4 g/kg, subcutaneous route) or saline (1 ml/kg) from 5 to 14 postnatal day (PND) to induce obesity with consequent damages in the liver. 4-PSQ treatment (5 mg/kg) or canola oil (1 ml/kg) was administered from 60 to 76 PND by the intragastric route. On 76 PND, animals were anesthetized for blood and liver collection. Plasma markers of hepatic function, hepatic lipoperoxidation levels and histology analysis of liver tissue were assessed., Key Findings: Our data revealed that treatment with 4-PSQ reverted the increase in plasma transaminases activities observed in MSG rats. Treatment with 4-PSQ reduced plasma lactate levels in obese rats. In the liver, MSG elevated the content of lipoperoxidation which was reverted by 4-PSQ administrations. Lastly, 4-PSQ therapy attenuated the histological alterations induced by MSG., Significance: Together, the results indicate a hepatoprotective action of repeated treatment with 4-PSQ in obese rats., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In early December 2019, an outbreak of coronavirus disease 2019 caused by a new strain of coronavirus (SARS-CoV-2), occurred in the city of Wuhan, Hubei Province, China. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern. Since then, frontline healthcare professionals have been experiencing extremely stressful situations and damage to their physical and mental health. These adverse conditions cause stress and biochemical, hematological, and inflammatory changes, as well as oxidative damage, and could be potentially detrimental to the health of the individual. The study population consisted of frontline health professionals working in BHU in a city in southern Brazil. Among the 45 participants, two were infected with the SARS-CoV-2 virus and were diagnosed using immunochromatographic tests such as salivary RT-LAMP and qRT-PCR. We also evaluated biochemical, hematological, inflammatory, and oxidative stress markers in the participants. The infected professionals (CoV-2-Prof) showed a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, lactic dehydrogenase, lymphocytes, and monocytes. In this group, the levels of uric acid, triglycerides, leukocytes, neutrophils, hemoglobin, hematocrit, and platelets decreased. In the group of uninfected professionals (NoCoV-2-Prof), significant increase in HDL levels and the percentages of eosinophils and monocytes, was observed. Further, in this group, uric acid, LDH, triglyceride, and cholesterol levels, and the hematocrit count and mean corpuscular volume were significantly reduced. Both groups showed significant inflammatory activity with changes in the levels of C-reactive protein and mucoprotein. The NoCoV-2-Prof group showed significantly elevated plasma cortisol levels. To our kowledge, this study is the first to report the use of the RT-LAMP method with the saliva samples of health professionals, to evalute of SARS-CoV-2., (Copyright © 2021. Published by Elsevier Ltd.)

Suppressive effect of bis (3-amino-2-pyridine) diselenide (BAPD) on psychiatric disorders - atopic dermatitis (AD) comorbidity in mice was investigated. To sensitize the animals, 2,4-dinitrochlorobenzene (DNCB) was applied to their dorsal skin on days 1-3. Mice were challenged with DNCB on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. BAPD and Dexamethasone were administered to the animals, from days 14-29, and skin severity scores and behavioral tests were determined. Oxidative stress and inflammatory parameters were evaluated on the dorsal skin of mice. Na + , K + -ATPase activity and corticosterone levels were determined in hippocampus/cerebral cortex and plasma of mice, respectively. BAPD improved cutaneous damage, scratching behavior, inflammatory and oxidative stress markers. BAPD showed anxiolytic- and antidepressant-like effects and restored Na + , K + -ATPase activity and corticosterone levels. The present study was performed using female mice due the susceptibility for this disease. But, the evaluation of AD model in male mice would help to verify whether the male gender has the same predisposition to present this pathology. Our data demonstrated the suppressive effect of BAPD on psychiatric disorders - AD comorbidity by regulating inflammatory and oxidative status in mice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses., Objective: The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats., Methods: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed., Results: MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa + /K + -ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment., Conclusions: In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.

Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that can stop this disease. To investigate the binding affinity of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) with acetylcholinesterase (AChE), to verify the effects of FSP in an AD model in mice and to evaluate the toxicological potential of this compound in mice. The binding affinity of FSP with AChE was investigated by molecular docking analyses. The AD model was induced by streptozotocin (STZ) in Swiss mice after FSP treatment (1 mg/kg, intragastrically (i.g.)), 1st-10th day of the experimental protocol. Anxiety was evaluated in an elevated plus maze test, and memory impairment was evaluated in the Y-maze, object recognition and step-down inhibitory avoidance tasks. The cholinergic system was investigated based on by looking at expression and activity of AChE and expression of choline acetyltransferase (ChAT). We evaluated expression and activity of Na + /K + -ATPase. For toxicological analysis, animals received FSP (300 mg/kg, i.g.) and aspartate aminotransferase, alanine aminotransferase activities were determined in plasma and δ-aminolevulinate dehydratase activity in brain and liver. FSP interacts with residues of the AChE active site. FSP mitigated the induction of anxiety and memory impairment caused by STZ. FSP protected cholinergic system dysfunction and reduction of activity and expression of Na + /K + -ATPase. FSP did not modify toxicological parameters evaluated and did not cause the death of mice. FSP protected against anxiety, learning and memory impairment with involvement of the cholinergic system and Na + /K + -ATPase in these actions.

There is an increasing incidence of hepatotoxicity induced by oxaliplatin (OXA); therefore, researchers' attention has been drawn to therapeutic alternatives that may decrease OXA-induced hepatotoxicity. Studies indicate that oxidative stress plays a major role in OXA-induced liver injury. As several pharmacological effects of 7-chloro-4-(phenylselanyl) quinole (4-PSQ) involve its antioxidant action, the hypothesis that this organoselenium compound could be promising for the treatment or prevention of hepatotoxicity induced by treatment with OXA was investigated. To test this hypothesis, male Swiss mice received OXA (10 mg·kg -1 ) on days 0 and 2, followed by oral administration of 4-PSQ (1 mg·kg -1 ) on days 2 to 14. 4-PSQ reduced the plasma aspartate, and alanine aminotransferase activity increased by exposure to OXA. The histopathological examination of the liver showed that 4-PSQ markedly improved OXA-induced hepatic injury. In addition, treatment with 4-PSQ reduced the oxidation of lipids and proteins (thiobarbituric acid reactive species levels and protein carbonyl content) and attenuated the increase of hepatic catalase and glutathione peroxidase activity caused by OXA. The inhibition of hepatic δ-aminolevulinic dehydratase activity induced by OXA was reverted by 4-PSQ. In conclusion, results indicate that 4-PSQ may be a good therapeutic strategy for attenuating OXA-induced liver damage.

In this study, the deposition of platinum in oxaliplatin (OXA)-exposed mice and the effects of the oxidative damage on the central nervous system were investigated. The relationship between the reactive species (RS) levels as well as the expression and activity of enzymes, such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and acetylcholinesterase (AChE), in the development of peripheral neuropathy after OXA exposure, was evidenced. The effects of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on OXA-induced peripheral neuropathy was also investigated. Swiss mice received OXA (10 mg kg -1 ) or vehicle by intraperitoneal route (days 0 and 2). Oral administration of 4-PSQ (1 mg kg -1 ) or vehicle was performed on days 2 to 14. Behavioural tasks started on day 9, after the first OXA administration. It was observed that 4-PSQ reduced the mechanical and thermal hypersensitivity induced by OXA. 4-PSQ and OXA did not affect locomotor and exploratory activities. The results revealed, for the first time, a high concentration of platinum in the spinal cord of mice exposed to OXA. 4-PSQ reversed the increased levels of RS in the spinal cord, cerebral cortex and hippocampus of mice exposed to OXA. The alterations in the activity and expression of the GPx, SOD, CAT and AChE induced by OXA exposure were normalized by 4-PSQ. Therefore, the 4-PSQ might be a good prototype for the development of a more effective drug for the treatment of OXA-induced peripheral neuropathy. The results obtained by the present study expanded the knowledge about the mechanisms involved in the physiopathology of peripheral neuropathy. Graphical abstract.

An alternative method to prepare 2-organylchalcogenopheno[2,3-b]pyridines was developed by the insertion of chalcogen species (selenium, sulfur or tellurium), generated in situ, into 2-chloro-3-(organylethynyl)pyridines by using the NaBH 4 /PEG-400 reducing system, followed by an intramolecular cyclization. It was possible to obtain a series of compounds with up to 93 % yield in short reaction times. Among the synthesized products, 2-organyltelluropheno[2,3-b]pyridines have not been described in the literature so far. Moreover, the compounds 2-phenylthieno[2,3-b]pyridine (3 b) and 2-phenyltelluropheno[2,3-b]pyridine (3 c) exhibited significant antioxidant potential in different in vitro assays. Further studies demonstrated that compound 3 b exerted an antinociceptive effect in acute inflammatory and non-inflammatory pain models, thus indicating the involvement of the central and peripheral nervous systems on its pharmacological action. More specifically, our results suggest that the intrinsic antioxidant property of compound 3 b might contribute to attenuating the nociception and inflammatory process on local injury induced by complete Freund's adjuvant (CFA)., (© 2020 Wiley-VCH GmbH.)

Recently, we demonstrated the promising anxiolytic action of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) in mice. For this reason, the objective of this study was to expand our previous findings by investigating the contribution of serotoninergic and GABAergic systems to the anxiolytic action of this compound. Pretreatment with different serotoninergic antagonists (pindolol, WAY100635 and ketanserin) blocked the anxiolytic effect caused by 4-PSQ (50 mg/kg, per oral) in the elevated plus maze (EPM) test. The contribution of the GABAergic system was investigated by pretreatment with pentylenetetrazole (a GABA A receptor antagonist) (PTZ). 4-PSQ diminished the PTZ-induced anxiety, and did not modify the locomotor, exploratory and motor activities of mice. Later, this group of animals was euthanized and the blood was removed to determine the levels of corticosterone, and cerebral cortex and hippocampus to determine the mRNA expression levels of cAMP response element binding protein (CREB), brain derived neurotrophic factor (BDNF) and nuclear factor kappa B (NF-κB), as well as the Na + , K + ATPase activity and reactive species (RS) levels. 4-PSQ was able to significantly reverse the increase in RS and corticosterone levels, as well as the decrease of CREB and BDNF expression in the cerebral structures and increase of NF-κB expression in the hippocampus. Finally, 4-PSQ restored the Na + , K + ATPase activity in the cerebral structures evaluated. Here, we showed that the modulation of serotonergic and GABAergic systems, factors related to neurogenesis, oxidative status and Na + , K + ATPase activity contributes to the anxiolytic effect of 4-PSQ and reinforces the therapeutical potential of this compound for the treatment of anxiety., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Growing evidence demonstrates that Oxaliplatin (OXA) is commonly associated with neurotoxicity that leads to emotional and cognitive impairments. The aim of the present study was to evaluate the OXA and Na + , K + -ATPase interaction and to correlate anxious behavior and cognitive impairment induced by this chemotherapeutic in Swiss mice. Also, considering the pharmacological modulation of Na + , K + -ATPase as a potential target for OXA-induced neurotoxicity, the therapeutic potential of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) was evaluated. Mice received OXA (10 mg kg -1 ) or vehicle by intraperitoneal route (days 0 and 2). Oral administration of 4-PSQ (1 mg kg -1 ) or vehicle was performed from days 2-14. Behavioral tasks started from day 12 onwards. On day 15, the animals were sacrificed, and the tissues collected. The effects of OXA and 4-PSQ on activity and expression level of Na + , K + -ATPase in the hippocampus and cerebral cortex, and the plasmatic corticosterone levels were determined. The findings demonstrated a significant positive correlation between anxious behavior and cognitive impairment induced by OXA. OXA caused an increase on the plasmatic corticosterone levels and reduced activity and expression level of Na + , K + -ATPase. 4-PSQ reduced both anxious behavior and cognitive impairment induced by OXA. 4-PSQ effect seems to be due to the modulation of Na + , K + -ATPase and reduction of corticosterone levels. Our results helped to expand knowledge about the mechanisms involved in the physiopathology of the OXA-induced neurotoxicity and strongly indicated that 4-PSQ may be a good prototype for the treatment of anxious behavior and cognitive impairment induced by OXA exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with nasty effects on the psychosocial wellbeing of patients. Overall, glucocorticoids, such as hydrocortisone (HC), are the primary pharmacologic drugs used to treat AD and its symptoms. However, the long-term treatment with HC is often accompanied by severe adverse effects. So, this study reports the encapsulation of HC in polymeric films based on gelatin (Gel) and gelatin/starch (Gel/St) and investigates their potential to treat and attenuate 2,4-Dinitrochlorobenzene (DNCB)-induced AD-like symptoms in BALB/c mice model. The prepared films were characterized by different techniques, which indicated that HC was physically entrapped into the polymer matrices. In vitro experiments indicate that the HC release process occurs in a controlled manner (up to 48 h) for both films. Regarding the in vivo experiments, HC-loaded films (Gel@HC and Gel/St@HC), unloaded films (Gel and Gel/St) and HC cream (1%) (as reference) were applied topically on the back of the DNCB-sensitized animals and skin severity scores and scratching behavior were determined. Ex-vivo experiments were done to quantify inflammatory and/or biochemical parameters. As assessed, the topical application of the biopolymeric films (loaded or not with HC) improved the inflammatory parameters, while a lower corticosterone level was observed for the animals treated with Gel and Gel@HC films. In summary, the HC-loaded films showed superior efficiency to treat/attenuate the analyzed parameter than the HC cream (1%). Further, no death or sign of toxicity was observed in animals exposed to HC-loaded films. Thus, the encapsulation of HC in biopolymeric films seems to be a promising alternative for the treatment of injuries caused by chronic skin diseases that require prolonged use of glucocorticoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A new series of Cu(II) complexes [bis[{(μ 2 -chloro)-2-MeO-Ph-CH 2 -(N=CH)-2,4-tert-butyl-2-OC 6 H 2 )}Cu(II)] (Cu1); bis[{(μ 2 -chloro)-2-MeS-Ph-CH 2 -(N=CH)-2,4-tert-butyl-2-(OC 6 H 2 )}Cu(II)] (Cu2); bis[{(μ 2 -chloro)-2-MeO-Ph-CH 2 -(N=CH)-2-(OC 10 H 6 )} Cu(II)] (Cu3); bis[{(μ 2 -chloro)-2-MeS-Ph-CH 2 -(N=CH)-2-(OC 10 H 6 )}Cu(II)] complex (Cu4); bis[{2-MeS-Ph-CH 2 -(N=CH)-2,4-tert-butyl-2-(OC 6 H 2 )}Cu(II)] (Cu5)] have been synthesized and characterized by elemental analysis, IR, UV-Visible and by X-ray crystallography for Cu1, Cu4 and Cu5. In the solid state, Cu1 features of a chloro-bridged dimer complex with κ 2 coordination of the monoanionic phenoxy-imine ligand onto the copper center. On the other hand, the molecular structure of Cu4 reveals the naphthoxy-imine ligand with pendant S-group coordinated to the copper atom in tridentate meridional fashion. Treatment of [Cu(OAc) 2 ·H 2 O] with two equiv. of [2-MeS-Ph-CH 2 -(N=CH)-2,4-tert-butyl-2-(HOC 6 H 2 )] led to a monomeric complex Cu5, with the ONS-donor Schiff base acting as a bidentate ligand. The redox behavior was explored by cyclic voltammetry. The reduction/oxidation potential of Cu(II) complexes depends on the structure and conformation of the central atom in the coordination compounds. Antioxidant activities of the complexes, Cu1 - Cu5, were determined by in vitro assays such as 1,1-diphenyl-2-picryl-hydrazyl free radicals (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS + ). The dinuclear compounds Cu1-Cu4, from the concentration of 5 μM, presented a good activity in scavenging DPPH radical. In addition, most of the Cu(II) complexes showed ABTS .+ radical-scavenging activity. The monomeric complex Cu5 at all concentrations tested showed antioxidant inability. The cytotoxicity of the Cu1 and Cu3 was determined in V79 cell line by reduction of 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two new selanyl amide derivatives in cerebral structures of mice. Our results demonstrated that N -(2-(3-(phenylselanyl)propoxy)phenyl)furan-2-carboxamide ( 1 ) and N -(2-(3-(phenylselanyl)propoxy)phenyl)thiophene-2-carboxamide ( 2 ) inhibited the in vitro AChE activity in mice. Another objective was to assess the effect of the best AChE inhibitor in an amnesic model induced by scopolamine (SCO) in male Swiss mice. The involvement of AChE activity and lipid peroxidation in the cerebral structures was investigated. Our results showed that compound 1 (10 mg/kg, intragastrically) attenuated the latency to find the escape box and the number of holes visited in the Barnes maze task, without altering the locomotor and exploratory activities in an open-field test. Compound 1 protected against increasing in lipid peroxidation levels and AChE activity caused by SCO in the cerebral cortex and hippocampus of mice. In conclusion, the present study evidenced the in vitro anticholinesterase effect of two new selanyl amide derivatives in the cerebral structures of mice. Moreover, compound 1 , a selanyl amide derivative containing a furan ring, demonstrated antiamnesic action due to its antioxidant and anticholinesterase activities in cerebral structures.

The present study evaluated the anti-amnesic activity of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) against scopolamine (SCO)-induced amnesia in mice. It was evaluated cholinergic dysfunction, oxidative stress and Na + /K + -ATPase activity in cerebral cortex and hippocampus of mice. Male Swiss mice were treated with QTCA-1 (10 mg/kg, intragastrically (i.g.), daily) for nine days. Thirty minutes after the treatment with compound, the animals received a injection of SCO (0.4 mg/kg, intraperitoneally (i.p.)). Mice were submitted to the behavioral tasks 30 min after injection of SCO (Barnes maze, open-field, object recognition and location, and step-down inhibitory avoidance tasks) during nine days. In day 9, cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) levels, and catalase (CAT), Na + /K + -ATPase and acetylcholinesterase (AChE) activities. SCO caused amnesia in mice for changing in step-down inhibitory avoidance, Barnes maze, and object recognition and object location tasks. QTCA-1 treatment attenuated the behavioral changes caused by SCO. Moreover, SCO increased AChE and CAT activities, decreased Na + /K + -ATPase activity and increased TBARS levels in the cerebral structures of mice. QTCA-1 protected against these brain changes. In conclusion, QTCA-1 had anti-amnesic action in the experimental model used in the present study, through the anticholinesterase effect, modulation of Na + /K + -ATPase activity and antioxidant action.

This study investigated whether subacute treatment with 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) presented antioxidant action in oxidative stress associated with aging in different rat tissues. We also investigated whether plasma selenium levels were altered by aging, as well as the contribution of 4-PSQ administration to these levels. Aged Wistar male rats (23month old) were intragastrically treated with 4-PSQ (5mg/kg) for seven days. On the 14th day of the experimental protocol, plasma was collected to determine selenium levels and biochemical markers of renal and hepatic damage. Furthermore, liver, kidney, spleen and cerebral cortex were removed to determine thiobarbituric acid reactive species (TBARS), non-protein thiols (NPSH), glutathione S-transferase (GST), catalase (CAT) and δ-aminolevulinate dehydratase (ALA-D). Our results showed that one or more parameters changed markedly in the liver, kidney, spleen and cerebral cortex of aged rats. Moreover, biochemical markers of renal and hepatic damage and selenium levels are changed in the plasma of aged rats. Treatment with 4-PSQ repaired redox homeostasis in tissues of aged rats, as well as plasma biochemical markers of renal and hepatic damage and selenium levels. In conclusion, 4-PSQ presented an antioxidant effect in tissues of aged rats, restoring selenium levels, and contributing to the restoration of the damage caused by aging. Thus, 4-PSQ could be a potential candidate for the management of age-related oxidative damage, acting as an anti-aging drug., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The present study evaluated the antioxidant, antinociceptive and anti-edematogenic effects of Se-[(2,2-dimethyl-1,3-dioxolan-4-yl) methyl] 4-chlorobenzoselenolate (Se-DMC)., Methods: In vitro experiments were carried out to evaluate Se-DMC antioxidant action. Thiobarbituric acid reactive species levels, 2,2'-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-thylbenzthiazoline-6-sulfonic acid) radicals scavenging and glutathione S-transferase-like activity were determined. Male Swiss mice were orally pretreated with Se-DMC (1, 10 and 50 mg/kg), meloxicam (50 mg/kg) or vehicle 30 min prior to acetic acid or glutamate test. To extend our knowledge of the pharmacological properties of this compound, it was tested in an inflammatory model through ear edema induced by croton oil. The contribution of glutamatergic and serotonergic systems was also investigated., Results: In vitro experiments revealed that Se-DMC exerts antioxidant activity. Nociception induced by glutamate or acetic acid was reduced by Se-DMC or meloxicam. Se-DMC diminished the paw edema formation induced by glutamate, while meloxicam did not show any effect. Se-DMC and meloxicam decreased the ear edema formation and protected against the increase in myeloperoxidase activity in mice ear induced by croton oil. The pretreatment of animals with MK-801 did not alter antinociception caused by Se-DMC in the glutamate test. The antinociceptive effect exerted by Se-DMC in the acetic acid test was reverted by the pretreatment of mice with different serotonergic antagonists (WAY100635, ketanserin and pindolol)., Conclusions: Data presented here showed that the modulation of serotonergic and glutamatergic systems and the anti-inflammatory and antioxidant actions could contribute to the antinociceptive and anti-edematogenic effects of Se-DMC and it supported the therapeutic potential of this compound., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Herein, we describe a new strategy to prepare chalcogen-functionalized isoxazolines. The strategy involves the reaction of β,γ-unsaturated oximes with electrophilic selenium and tellurium species, affording 19 new selenium- and tellurium-containing isoxazolines in good yields after 1 h at room temperature. The method was efficiently extended to the synthesis of 5 new (bis)isoxazoline ditellurides. One of the prepared compounds, 3-phenyl-5-((phenylselanyl)methyl)-isoxazoline, demonstrated better anti-inflammatory and antiedematogenic effects than the reference drug Celecoxib.

The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na + , K + -ATPase activities in prefrontal cortex of mice. BMMS, (0.1-10 mg/kg, intragastrically (i.g.)) and fluoxetine (32 mg/kg, i.g.) decreased the immobility time in the FST and TST. The anti-immobility effect of BMMS (10 mg/kg, i.g.) in the TST was prevented by the pretreatment of mice with WAY100635 (0.1 mg/kg, subcutaneously (s.c.), a 5-HT 1A receptor antagonist), ketanserin (5 mg/kg, intraperitoneal (i.p.), a 5-HT 2A/2C receptor antagonist), and partially blocked by ondansetron (1 mg/kg, i.p., a 5-HT 3 receptor antagonist). The anti-immobility effect of BMMS (10 mg / kg, i.g.) was not avoided by pretreatment with MK-801 (0.01 mg/kg, s.c. a non-competitive N-methyl D-Aspartate (NMDA) receptor) in the TST. Pretreatment with L-arginine (500 mg/kg, i.p., a nitric oxide precursor) reversed partially the reduction in the immobility time elicited by BMMS (10 mg/kg, i.g.) in TST. BMMS altered Na + ,K + -ATPase and MAO-A activities in prefrontal cortex of mice, but was not able to change the MAO-B activity. In conclusion, BMMS exerted an antidepressant-like effect in mice and serotonergic and nitrergic systems are involved in the antidepressant-like action of compound. BMMS modulated MAO-A and Na + , K + - ATPase activities in prefrontal cortex of mice.

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) to restore the cognitive impairment caused by aging in male Wistar rats. Moreover, modulation of neuroplasticity markers, acetylcholinesterase (AChE) activity, and cholesterol levels was performed. Aged rats were intragastrically treated with 4-PSQ (5 mg/kg) for 7 days. Animals were tested in behavioral tasks, and then plasma (to determine cholesterol levels), hippocampus, and cerebral cortex (to determine neural cell adhesion molecule (NCAM) and polysialyltransferase (PST) levels, and AChE activity) were removed. Our findings demonstrated that treatment of aged rats with 4-PSQ restored short-term and long-term memories in the object recognition tests. 4-PSQ treatment did not restore exploratory activity (rearings) but partially restored locomotor activity (crossings) reduced by aging in the open-field test. Moreover, the compound restored the reduction in the NCAM and PST levels, and AChE activity in cerebral structures, as well as the increase in the plasma cholesterol levels, caused by aging in rats. In conclusion, 4-PSQ restored cognitive impairment caused by aging in rats by modulating synaptic plasticity, cholinergic system, and cholesterol levels.

In this study, Schiff bases of chitosan (CS) were synthesized using citronellal, citral, and their derivatives containing selenium and sulfur. Organoselenium and organosulfur compounds show attractive biological and pharmaceutical activities, which can be beneficial to CS-based materials. From the characterization analyses, it was found that the CS-derivatives containing organoselenium and organosulfur compounds exhibited the highest conversion degrees (23 and 28%). Biological assays were conducted using films prepared by the blending of CS-derivatives and poly(vinyl alcohol). The antimicrobial evaluation indicated that the film prepared with the sulfur-containing CS was the most active against the tested pathogens (Escherichia coli, Staphylococcus aureus, and Candida albicans) since it reduced considerably their counts (42.5%, 17.4%, and 18.7%). Finally, in vivo assays revealed that this film attenuates atopic dermatitis-like symptoms in mice by suppressing the increase of myeloperoxidase (MPO) activity and reactive species (RS) levels induced by 2,4-dinitrochlorobenzene (DNCB). In summary, CS-derivatives containing chalcogens, mainly organosulfur, are potential candidates for biomedical applications such as for the treatment of chronic skin diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In the present study, the synthesis of new selenoethers from nucleophilic substitution reaction between organyl halides and nucleophilic species of selenium generated in situ was demonstrated. After, this method was applied for the synthesis of pyridylselenides glycerol derivatives 9b and 9c and the antinociceptive and anti-inflammatory effects, as well as, acute toxicity were evaluated. In the formalin test, the compound 9b caused a reduction in licking time in both phases. Compounds 9b and 9c increased the latency to response in the hot-plate test and reduced the licking time induced by glutamate. Our results revealed the involvement of the nitrergic and/or glutamatergic pathways in the antinociceptive action of the compounds. Additionally, 9b and 9c did not cause any toxicity signals and oxidative stress parameters were not modified by treatments. Here, it was developed an alternative and efficient method for the synthesis of selenoethers glycerol derivatives. Furthermore, we demonstrated that this class is indeed interesting for the research of new drugs. Graphical Abstract ᅟ.

Determining precisely the postmortem interval (PMI) is a key parameter for forensic researches, given that various physical, biochemical and metabolic changes begin to occur in the body after death. In the present study, the Na + /K + -ATPase, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were evaluated. For this, male adult Swiss mice were killed by isoflurane inhalation anesthesia and divided into four groups according to time of death (0, 6, 24 and 48 h). The brain, liver, kidney and skeletal muscle tissues were removed. Our results revealed that at the time of 6 h, there was a decrease on Na + /K + -ATPase and GST activities in the brain and liver tissues, respectively. In addition, at this time point, an increase on renal GST activity was verified. At the time of 24 h, an increase on the cerebral AChE and renal GST activities was observed, while the cerebral Na + /K + -ATPase activity was decreased. Forty-eight hours after death, cerebral Na + /K + -ATPase and renal GST activities remained decreased and increased, respectively. In addition, no alteration was observed on the GST activity in the skeletal muscle and brain (in PMIs evaluated). The present study revealed that the brain and kidney (at the times of 24 and 48 h) were the tissues that suffered the most changes in almost all the enzymes evaluated. Our results demonstrated that enzyme activity assessments are reliable, easy-to-perform and low-cost determinations, and could be promising postmortem markers., (Copyright © 2018 Elsevier B.V. All rights reserved.)