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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.)

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.)

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.)

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.)

The quinolone compounds have been reported for many biological properties, especially as potent antioxidants. This study investigated the antioxidant effect of 7-chloro-4-phenylselenyl-quinoline (PSQ), a quinolone derivative with organoselenium group, against oxidative stress induced by sodium nitroprusside (SNP) in brains of mice. A second objective was to verify the importance of phenylselenyl group presents at position 4 of the quinoline structure to antioxidant effect of compound. So, it was compared the antioxidant effect of PSQ with a quinoline without organoseleniun group (7-chloroquinoline [QN]). Swiss mice were used and received SNP (0.335 μmol/site, intracerebroventricular) 30 min after treatment with PSQ or QN, at the doses of 50 mg/kg (intragastrically). After 1 h, animals were sacrificed and the brains were removed to biochemistry analysis. Thiobarbituric acid reactive species (TBARS), protein carbonyl (PC) and non-protein thiol (NPSH) levels, as well as catalase (CAT), glutathione S transferase (GST) and δ -aminolevulinic acid (δ-ALA-D) activities were determined. SNP increased TBARS and PC levels, and reduced the enzymatic (CAT and GST activity) and non-enzymatic (NPSH levels) antioxidant defenses and inhibited the δ-ALA-D activity. PSQ avoided the increase in the lipid peroxidation and PC levels, as well as the decrease in the NPSH levels, CAT, GST and δ-ALA-D activities QN partially avoided the increase in lipid peroxidation, but it not protected against alterations induced by SNP. In conclusion, phenylselenyl group present in quinoline structure is critical for antioxidant activity of PSQ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Unsymmetrical dichalcogenides, a class of organoselenium compounds, were screened for antioxidant activity in rat brain homogenates in vitro. Unsymmetrical dichalcogenides (1-3) were tested against lipid peroxidation induced by sodium nitroprusside (SNP) or malonate, and reactive species (RS) production induced by sodium azide in rat brain homogenates. Compounds 1 (without a substituent at the phenyl group), 2 (chloro substituent at the phenyl group bounded to the sulfur atom) and 3 (chloro substituent at the phenyl group bounded to the selenium atom) protected against lipid peroxidation induced by SNP. The IC50 values followed the order 3<2<1. Lipid peroxidation induced by malonate was also reduced by dichalcogenides 1, 2 and 3. The IC50 values were 3