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Meloxicam is the non-steroidal anti-inflammatory drug most used in small animals; however, studies on genotoxicity, oxidative stress, and histopathologic alterations in cardiac tissue are limited, especially at therapeutical doses used in these animals. This study evaluated the toxic effects caused by the treatment involving repeated low at higher doses of meloxicam in mice, by genotoxicity, oxidative stress, and histopathological parameters. Mice (CF1, male) received, by gavage, meloxicam at the therapeutic dose indicated for small animals (0.1 mg/kg) and at higher doses (0.5 and 1 mg/kg) for 28 days. Later, they were euthanized for blood and organ analysis. Oxidative stress was analyzed by the plasma ferric reduction capacity (FRAP) and catalase, and genotoxicity, by the comet assay and the micronucleus test. Heart, liver, lung, and kidney tissues were analyzed by the histology, and stomach and duodenum were analyzed with a magnifying glass. The relative weight of organs did not present significant alterations. However, congestion of duodenum vessels was observed at the three tested doses and caused hyperemia of stomach mucosa at 1 mg/kg. In the heart histology there was a reduction in the number of cardiomyocytes, accompanied by an increase in cell diameter (possible cell hypertrophy) dose-dependent. The highest tested dose of meloxicam also increased the DNA damage index, without alterations in the micronucleus test. Meloxicam did not affect the catalase activity but increased the FRAP (1 mg/kg). Meloxicam at the dose prescribed for small animals could potentially cause cardiac histopathologic alterations and genotoxic effects. [ABSTRACT FROM AUTHOR]

Glyphosate is the active ingredient and polyoxyethyleneamine is the surfactant present in the herbicide Roundup® formulation commercialized in Brazil. The aim of this study was to assess the reproductive effects of glyphosate-Roundup® on male and female offspring of Wistar rats exposed during pregnancy and lactation. Dams were treated orally with water or 50, 150 or 450 mg/kg glyphosate during pregnancy (21–23 days) and lactation (21 days). These doses do not correspond to human exposure levels. The results showed that glyphosate-Roundup® did not induce maternal toxicity but induced adverse reproductive effects on male offspring rats: a decrease in sperm number per epididymis tail and in daily sperm production during adulthood, an increase in the percentage of abnormal sperms and a dose-related decrease in the serum testosterone level at puberty, and signs of individual spermatid degeneration during both periods. There was only a vaginal canal-opening delay in the exposed female offspring. These findings suggest that in utero and lactational exposure to glyphosate-Roundup® may induce significant adverse effects on the reproductive system of male Wistar rats at puberty and during adulthood. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the teratogenicity of the herbicide glyphosate-Roundup® (as commercialized in Brazil) to Wistar rats. Dams were treated orally with water or 500, 750 or 1000 mg/kg glyphosate from day 6 to 15 of pregnancy. Cesarean sections were performed on day 21 of pregnancy, and number of corpora lutea, implantation sites, living and dead fetuses, and resorptions were recorded. Weight and gender of the fetuses were determined, and fetuses were examined for external malformations and skeletal alterations. The organs of the dams were removed and weighed. Results showed a 50% mortality rate for dams treated with 1000 mg/kg glyphosate. Skeletal alterations were observed in 15.4, 33.1, 42.0 and 57.3% of fetuses from the control, 500, 750 and 1000 mg/kg glyphosate groups, respectively. We may conclude that glyphosate-Roundup® is toxic to the dams and induces developmental retardation of the fetal skeleton. [Copyright &y& Elsevier]

Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175–5,000 mg·kg−1) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p < 0.05) after 14 days. We found statistical differences for hematological and biochemical parameters, unrelated to dosage. There were no observed toxic effects, and tobacco stalk ingestion did not adversely affect organ morphology in the histopathological evaluation. The oral administration of NFC at 5,000 mg·kg−1 per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications. [ABSTRACT FROM AUTHOR]

Introduction Chloroquine and hydroxychloroquine are antimalarial drugs widely used in the treatment of rheumatic diseases. With the global pandemic caused by the new coronavirus, there was an increase in the prescription of these drugs, which led to a major concern regarding their ototoxic effects. Objectives The objective of the present study was to assess existing scientific evidence about the toxic effects of chloroquine and hydroxychloroquine on the peripheral and/or central auditory system. Data Synthesis A systematic literature review was performed by searching the PubMed (Medline), Scopus, Web of Science, LILACS, and SciELO electronic databases, in a search of articles that fullfiled the predefined inclusion and exclusion criteria. The review was conducted in three phases and, in all of them, analyses were performed by two independent researchers. Disagreements were discussed with a third researcher until a consensus was reached. A total of 437 articles were found and 8 were included in this review. Seven of the included studies reported hearing loss in their samples and presented a diagnostic hypothesis of ototoxicity induced by chloroquine or hydroxychloroquine. The most common type of hearing loss was sensorineural, with varying laterality and degrees of severity. The most frequently used audiological test was pure tone audiometry, and only two studies assessed brainstem evoked responses. Conclusion The scientific evidence compiled in this research showed that chloroquine and hydroxychloroquine have an ototoxic effect in the peripheral auditory system. These drugs can cause cochlear damage, including changes in the stria vascularis and lesions in sensory hair cells. [ABSTRACT FROM AUTHOR]

Phα1β, a purified peptide from the venom of the spider Phoneutria nigriventer, and its recombinant form CTK 01512-2 are voltage-dependent calcium channel (CaV) blockers of types N, R, P/Q, and L with a preference for type N. These peptides show analgesic action in different pain models in rats. The aim of this study was to evaluate the acute intrathecal toxicity of the native and recombinant Phα1β toxin in Wistar rats. Clinical signs, serum biochemistry, organ weight, and histopathological alterations were evaluated in male and/or female rats. Dyspnea was observed in males, hyporesponsiveness in females, and Straub tail and tremors in both genders. There were no significant differences in male organ weight, although significant differences in the female relative weight of the adrenal glands and spleen have been observed; these values are within the normal range. Serum biochemical data revealed a significant reduction within the physiological limits of species related to urea, ALT, AST, and FA. Hepatic and renal congestion were observed for toxin groups. In renal tissue, glomerular infiltrates were observed with increased glomerular space. These histological alterations were presented in focal areas and in mild degree. Therefore, Phα1β and CTK 01512-2 presented a good safety profile with transient toxicity clinical signals in doses higher than used to obtain the analgesic effect. [ABSTRACT FROM AUTHOR]

The current resistance status of mosquitos to common insecticides raises the concern for innovative formulations with novel active ingredients, especially for those who can transmit pathogens. In addition to being effective, these are not allowed to harm the environment and non-target organisms. In this context, some imidazolium salts are promising candidates due to their excellent larvicidal action against Aedes aegypti, however, the understanding of their impact on environment and non-target organisms is limited. Herein, the toxicity of two imidazolium salts (1-methyl-3-octadecylimidazolium chloride (C18MImCl) and 1-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS)) were tested in Culex quinquefasciatus larvae and their (cyto)toxic potential in Lactuca sativa seeds, mouse lung fibroblasts, human keratinocytes and Wistar rats.C16MImMeS showed excellent larvicidal activity (LC50: 24 h: 5.751 µg/mL; 48 h: 4.613 µg/mL), but negatively influenced the Lactuca sativa germination rate and size of radicles and hypocotyls, together with other phytotoxic characteristics. C18MImCl also showed being a potent larvicidal (LC50: 24 h: 3.848 µg/mL; 48 h: 3.175 µg/mL), without presenting phytotoxicity against Lactuca sativa.C16MImMeS was more cytotoxic to mouse lung fibroblast and human keratinocyte cells than C18MImCl. Besides, the lethal median toxicity of 309 mg/kg of C18MImCl for oral application in Wistar rats suggests its safe application in related non-target organisms. Altogether, this is the first work showing the larvicidal potential of these IS against Culex quinquefasciatus, including phytotoxicity and (cyto)toxicity data that are important for their release in mosquito controlling formulations. [ABSTRACT FROM AUTHOR]

Phytoestrogens, such as isoflavones, are bioactive compounds found in plants with defense and protection functions. In the human body, they simulate the behavior of the hormone estradiol and can modulate the function of the male hypothalamic–pituitary–gonadal axis. This study aims to describe the effects of genistein on sperm quality of Wistar rats (male/adult) after a short oral administration protocol (50 mg/day, for 5 days), focusing on mitochondrial function. No signs of toxicity were observed in the animals during the period. The testicular mass of rats from the genistein-treated group was lower than that from the control group. Isoflavone increased the number of viable Leydig and Sertoli cells, spermatogonia, and primary spermatocytes in the treated group. The rounded spermatid count was similar to the control group, and a decrease in elongated spermatids was observed in the treated group. Genistein treatment increased plasma testosterone levels in the treated group. To the best of our knowledge, this is the first report of an in vivo short protocol demonstrating that genistein administration stimulates the overall oxygen consumption in rat seminal samples. Therefore, genistein induced a pro-spermatogenesis effect, enhanced plasma testosterone levels, and increased oxygen consumption, improving sperm mitochondrial efficiency. Similar protocols can be explored in animal and human infertility issues. [ABSTRACT FROM AUTHOR]

Although Place Conditioning (PC) has been used to study the motivational effects of alcohol for almost 50 years, variables and situations in which alcohol induces PC in rats are still unclear, especially for short PC protocols (up to 10 conditioning trials). The aim of this systematic review was to predict primary outcomes (namely, conditioning failure, conditioned place aversion (CPA), and conditioned place preference (CPP)) of alcohol‐induced PC with male outbred rats. We sought relevant records in PUBMED and two other sources. Two reviewers independently assessed records for eligible articles (those meeting all inclusion criteria), selected alcohol‐induced PC experiments (those meeting no exclusion criteria) from eligible articles, extracted data, and assessed the quality of included studies. We then conducted a predictive analysis of outcomes by examining procedure‐outcome relations according to variables known to affect associative learning, alcohol interventions in rats, and PC interventions themselves. We selected 192 experiments (133 short protocols, 27 long protocols, and 32 protocols with alcohol pre‐exposure) from 62 articles to compose the review. Rates of conditioning failure are mainly predicted by interactions of alcohol dose and the number of habituation sessions and conditioning trials. Different conditions (housing systems) and characteristics (age and weight) of animals predict CPA and CPP: higher rates of CPA are predicted by single‐housed, older, and heavier animals, while higher rates of CPP are predicted by group‐housed, younger, and lighter animals. We recommend settings for CPP induction in short protocols, discuss the broad theoretical and translational consequences of the predictive analysis for the use of PC in alcohol research, and specify variables needing more careful investigation. This review could improve our understanding of the results of alcohol‐induced PC with rats, refine our understanding of the motivational function of alcohol and alcohol‐seeking behavior triggered by environmental contexts, and open new avenues of research on their neurobiological basis. [ABSTRACT FROM AUTHOR]

Activation of nociceptin opioid peptide receptors (NOP, a.k.a. opioid-like receptor-1, ORL-1) by the ligand nociceptin/orphanin FQ, leads to G protein-dependent regulation of Cav2.2 (N-type) voltage-gated calcium channels (VGCCs). This typically causes a reduction in calcium currents, triggering changes in presynaptic calcium levels and thus neurotransmission. Because of the widespread expression patterns of NOP and VGCCs across multiple brain regions, the dorsal horn of the spinal cord, and the dorsal root ganglia, this results in the alteration of numerous neurophysiological features. Here we review the regulation of N-type calcium channels by the NOP-nociceptin system in the context of neurological conditions such as anxiety, addiction, and pain. [ABSTRACT FROM AUTHOR]

Schizophrenia is a psychiatric disorder that affects 1% of the world population and is treated with antipsychotics, which may induce important biochemical and hematological alterations. Since it is necessary to verify the safety of new molecules with antipsychotic potential, the present study aimed to evaluate the oral toxicity of PT-31, a putative α2-adrenoreceptor agonist, after acute (2000 mg/kg) and repeated doses (28 days) gavage treatment, in three different doses: minimum effective dose in animal models (10 mg/kg), twice the dose (20 mg/kg), and four times the dose (40 mg/kg), as recommended by the OECD guidelines. Balb/C female adult mice were used, and biochemical, hematological, and histopathological analyses were performed. PT-31 10 and 20 mg/kg did not cause biochemical alterations related to hepatic and renal toxicity, and neither altered glycemic and lipid profiles. The preclinical dose of PT-31 also did not promote mice histopathological changes in the liver, kidney, and brain. In the hematimetric parameters, PT-31 only increased HGB at 20 mg/kg, and MCH and MCHC at 40 mg/kg. However, all the tested doses of PT-31 showed platelet increase, which must be better investigated. Therefore, further studies are needed to investigate the safety of PT-31 as a potential antipsychotic drug. [ABSTRACT FROM AUTHOR]

Objective: Circadian disturbances common to modern lifestyles have been associated with mood disorders. Animal models that mimic such rhythm disturbances are useful in translational research to explore factors contributing to depressive disorders. This study aimed to verify the susceptibility of BALB/c, C57BL/6N, and CF1 mice to photoperiod changes. Methods: Thermochron iButtons implanted in the mouse abdomen were used to characterize temperature rhythms. Mice were maintained under a 12:12 h light-dark (LD) cycle for 15 days, followed by a 10:10 h LD cycle for 10 days. Cosinor analysis, Rayleigh z test, periodograms, and Fourier analysis were used to analyze rhythm parameters. Paired Student's t test was used to compare temperature amplitude, period, and power of the first harmonic between normal and shortened cycles. Results: The shortened LD cycle significantly changed temperature acrophases and rhythm amplitude in all mouse strains, but only BALB/c showed altered period. Conclusion: These findings suggest that BALB/c, the preferred strain for stress-induced models of depression, should also be favored for exploring the relationship between circadian rhythms and mood. Temperature rhythm proved to be a useful parameter for characterizing rhythm disruption in mice. Although disruption of temperature rhythm has been successfully documented in untethered mice, an evaluation of desynchronization of other rhythms is warranted. [ABSTRACT FROM AUTHOR]

Mitoxantrone ( MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 ( MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 ( MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the Ig G levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. [ABSTRACT FROM AUTHOR]

Abstract: Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.), that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(ɛ-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245±10nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n =6/group) received a single-dose of saline solution (1.2ml/kg) or LNC (7.2×1012 LNC/kg), or repeated-doses of two controls, saline solution or Tween 80 (0.9ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4×1012 LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80–treated group (p <0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p <0.05) were found. Genotoxicity was evaluated through the comet assay, and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs. [Copyright &y& Elsevier]

Abstract: Hypericum polyanthemum, a South Brazilian species showed antidepressant-like and antinociceptive effects in rodents. Since limited information is available on the toxicity and safety profile of the Hypericum genus, we therefore investigated whether H. polyanthemum cyclo-hexane extract (POL) treatment could be associated with toxicity in preclinical setting using mice as an experimental model. These toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). Animals received POL single dose (2000mg/kg, p.o.) or daily for 28-days (90, 450 and 900mg/kg, p.o.). Acute toxicity study did not detect any clinical signs, changes in behavior or mortality. In repeated dose toxicity study, POL affected the body weight gain and induced biochemical, hematological and liver histological changes at 450 and 900mg/kg. Mice treated with POL 90mg/kg did not show any toxicity signs. In conclusion H. polyanthemum can be classified as safe (category 5) according to OECD acute toxicity parameters. However, the alterations observed after repeated treatment with high doses suggest that the liver could be the target organ on potential H. polyanthemum toxicity and point to the need of further toxicity studies. [Copyright &y& Elsevier]

Herpes simplex virus (HSV) 1 and 2 are viruses that infect individuals worldwide and for which there is no cure or vaccine available. The protective response against herpes is mostly mediated by CD8 T lymphocytes that respond to the immunodominant SSIEFARL epitope. However, there are some obstacles concerning the use of free SSIEFARL for vaccine or immunotherapy. The aim of this study was to evaluate the feasibility of nanoencapsulation of SSIEFARL and its immunostimulatory properties. Nano/SSIEFARL was produced by interfacial polymerization in methylmetacrylate, and the physico‐chemical properties, morphology and immunobiological parameters were evaluated. To evaluate the ex vivo capacity of Nano/SSIEFARL, we used splenocytes from HSV‐1‐infected mice to enhance the frequency of SSIEFARL‐specific CD8 T lymphocytes. The results indicate that Nano/SSIEFARL has a spherical shape, an average diameter of 352 ± 22 nm, the PDI was 0.361 ± 0.009 and is negatively charged (−26.30 ± 35). The stability at 4°C was 28 days. Also, Nano/SSIEFARL is not toxic for cells at low concentrations in vitro and it is taken up by JAWS II dendritic cells. No histopathological changes were observed in kidneys, liver and lymph nodes of animals treated with Nano/SSIEFARL. Nan/SSIEFARL increased the production of IL‐1β, TNF‐α and IL‐12 by the dendritic cells. Finally, Nano/SSIEFARL expanded the frequency of SSIEFARL‐specific CD8+T lymphocytes at the same rate as free SSIEFARL. In conclusion all data together indicate that SSIEFARL is suitable for nanoencapsulation, and the system produced presents some immunoadjuvant properties that can be used to improve the immune response against herpes. [ABSTRACT FROM AUTHOR]

Chronic opioid use changes brain chemistry in areas related to reward processes, memory, decision-making, and addiction. Both neurons and astrocytes are affected, ultimately leading to dependence. Passiflora incarnata L. (Passifloraceae) is the basis of frequently used herbals to manage anxiety and insomnia, with proven central nervous system depressant effects. Anti-addiction properties of P. incarnata have been reported. The aim of this study was to investigate the effect of a commercial extract of Passiflora incarnata (Sintocalmy®, Aché Laboratory) in the naloxone-induced jumping mice model of morphine withdrawal. In addition, glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) levels were assessed in the frontal cortex and hippocampus, and DNA damage was verified on blood cells. In order to improve solubilization a Sintocalmy methanol extract (SME) was used. SME is mainly composed by flavonoids isovitexin and vitexin. The effects of SME 50, 100 and 200 mg/kg (i.p.) were evaluated in the naloxone-induced withdrawal syndrome in mice. SME 50 and SME 100 mg/kg decreased naloxone-induced jumping in morphine-dependent mice without reducing locomotor activity. No alterations were found in GFAP levels, however SME 50 mg/kg prevented the S100B increase in the frontal cortex and DNA damage. This study shows anti-addiction effects for a commercial standardized extract of P. incarnata and suggests the relevance of proper clinical assessment. [ABSTRACT FROM AUTHOR]

3-nitropropionic acid (3-NP) is a toxin that causes neural damage in the striatum and can lead to the development of Huntington's disease manifestations in animal models. Several studies have shown genotoxicity related to the 3-NP treatment. This study investigated potential genotoxicity and mutagenicity that was induced by a low dose (6.25 mg/kg i. p.) 3-NP subacute treatment (daily, over 6 days) in a rat model. The arterial blood and the frontal cortex were analyzed by the comet assay and the bone marrow by micronucleus. Surprisingly, the 3-NP subacute treatment with the low dose did not show genotoxic or mutagenic effects. [Display omitted] • 3-NP subacute treatment with a low dose did not show genotoxic effects in the arterial blood. • The present work did not show genotoxic effects in the pre-frontal cortex. • There was no mutagenic effect in the bone marrow by the 3-NP subacute treatment. [ABSTRACT FROM AUTHOR]

Introduction: Nimesulide is a potent anti-inflammatory with rapid and long-lasting effects, but also with a high risk of hepatotoxicity. Objective: This work aimed to prevent nimesulide-induced hepatotoxicity through the association of nimesulide with a hepatoprotective agent. Materials and Methods: First, we tested three hepatoprotective agents: N-acetylcysteine, L-carnitine, and Gingko biloba extract in an in vitro hepatic cell model. Both N-acetylcysteine and G. biloba showed promisor results. We selected N-acetylcysteine to continue the studies in an animal model. In vivo study was performed using male Wistar rats divided in 4 groups: control, nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) + N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone (100mg/kg/day). Treatments were given by gavage, daily, for 15 days. Results: Animals receiving nimesulide alone showed lower body weight gain compared to control. Body weight gain in the nimesulide + N-acetylcysteine group was higher than nimesulide alone, evidencing lower toxicity. However, the body weight gain of the nimesulide + N-acetylcysteine group was still lower than the control animals. Animals treated with nimesulide alone presented an increased relative mass of heart, liver, and spleen and significant hepatic damage seen in microscopy when compared to other groups. N-acetylcysteine co-administered with nimesulide prevented the increased heart mass, but the same was not true with liver and spleen. Conclusions: This work evidence partial protection elicited by the association of N-acetylcysteine and nimesulide against nimesulide-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Phα1β peptide isolated from the venom of the Phoneutria nigriventer spider has shown higher analgesic action in pre‐clinical studies than ω‐conotoxin MVIIA peptide used to treat severe chronic pain. In view of the great potential for the development of a new Phα1β‐based drug, a Phα1β recombinant form (CTK 01512‐2) has been studied for efficacy and safety. The aim of this study was to evaluate cytotoxic, genotoxic and mutagenic effects of a Phα1β recombinant form and compare it with native Phα1β and ω‐conotoxin MVIIA. Cytotoxicity was evaluated using the MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide) colourimetric assay in L929 mouse fibroblast cells (0.5‐10.0 μmol/L). Genotoxic and mutagenic activities were analysed using the alkaline comet assay in peripheral blood and spinal cord, and the micronucleus test in bone marrow from Wistar rats treated by intrathecal injection of CTK 01512‐2 (200, 500 and 1000 pmol/site), native Phα1β (500 pmol/site) and ω‐conotoxin MVIIA (200 pmol/site). CTK 01512‐2 decreased the cell viability of the L929, showing IC50 of 3.3 ± 0.1 µmol/L, while the Phα1β and ω‐conotoxin MVIIA did not show cytotoxicity (IC50 > 5.0 µmol/L). Native and recombinant Phα1β forms induced DNA damage in the spinal cord, but not in peripheral blood. CTK 01512‐2 at 1000 pmol/site increased the micronucleus frequency suggesting mutagenic effects. In conclusion, the recombinant form has cytotoxic, genotoxic and mutagenic effects, evidenced in doses five times above the therapeutic dose. [ABSTRACT FROM AUTHOR]

Soy derivatives contain isoflavones with structural similarity to estrogen hormones known as phytoestrogens. The levels of isoflavones in these foods are quite variable and often unknown. The objective of this work was to develop and validate a methodology for the quantification of isoflavone genistein in soymilk by liquid chromatography coupled with an ultraviolet detector. After quantifying the levels of genistein in soymilk, the behavioral effects of daily administration of soymilk supplemented or not with glyphosate (50 or 100 mg/kg) throughout the pre-pubertal period in male rats were evaluated. The method developed is selective, sensitive, specific, and precise for the quantification of genistein with a total execution time of 20 min. Behavioral test highlights changes in anxiety pattern after chronic prepubertal exposure to soymilk containing 26.46 μg/mL genistein. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the acute toxicity of the association of energy drink and alcohol in male Wistar rats. Animals were treated by oral gavage with 10 ml/kg distilled water (control); 10 ml/kg energy drink (ED10); 3.2 mg/kg caffeine + 40 mg/kg taurine; 2 g/kg alcohol 20%; 2 g/kg alcohol 20% + ED10; and 2 g/kg alcohol 20% + 3.2 mg/kg caffeine + 40 mg/kg taurine. Behavioral alterations were observed for 6 h after treatment. Animals presented significant differences in the frequency of rearing, ambulation, grooming, wakefulness and tachypnea along time. Caffeine + taurine increased the levels of TBARS and total thiols in kidneys. ED10 increased lipoperoxidation in liver. The association of ED10 + alcohol induced nephrotoxicity observed by the increase of urinary N -acetyl-β- d -glucosaminidase (NAG) activity. Histopathological analysis showed the presence of congestion and hydropic and hyaline degenerations in the livers of ED10 + alcohol treated rats, and hemorrhage in the liver of alcohol + caffeine + taurine group. In kidneys, hyaline degeneration was observed in ED10; ED10 + alcohol; caffeine + taurine; and alcohol + caffeine + taurine. Hemorrhage was present in the kidneys of all groups. The combination of energy drinks and alcohol is not safe for the consumers. Therefore, precautionary measures should be disseminated among risk populations, especially the teenagers. [ABSTRACT FROM AUTHOR]

Abstract: Garcinielliptone FC (GFC) is a polyisoprenylated benzophenone isolated from Platonia insignis Mart (Clusiaceae) with promising anticonvulsant properties. However, its safe use and other effects on the central nervous system require assessment. This study assessed the toxicological effects of GFC using the comet assay and the micronucleus test in mice treated for 28 days. A behavioural model was employed to detect possible injuries on the central nervous system. Mice treated with GFC (2, 10 and 20 mg/kg; i.p.) daily for 28 days were submitted to rotarod test, open‐field test and tail suspension test (TST). After the behaviour tasks, biological samples were assessed to evaluate genotoxic and mutagenic effects using the comet assay and the micronucleus test. Garcinielliptone FC did not impair the performance of the animals in the rotarod and open‐field tests, with no antidepressant‐like effect in TST. No genotoxic effects in blood and cerebral cortex were observable in the comet assay; however, there was a significant increase in index and frequency of damage in liver after treatment with GFC 20 mg/kg. Garcinielliptone FC did not increase micronucleus frequency in bone marrow. At the tested doses, GFC was not toxic to the CNS and did not induce genotoxic damage to blood or bone narrow cells. DNA damage to liver tissue was caused only by the highest dose, although no mutagenic potential was observed. [ABSTRACT FROM AUTHOR]

Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing dairy milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control. [ABSTRACT FROM AUTHOR]

The consumption of energy drinks is common among adolescents and young adults. The possible effects (mainly behavioral and reproductive) of ingestion in this population remain unknown. For this reason, this study aimed to evaluate the behavioral and reproductive effects of energy drinks and their main constituents (caffeine and taurine), as well as their combinations with alcohol, via a binge drinking protocol in male and female Wistar rats during puberty. In this study, 100 male and 100 female rats were treated with a binge drinking protocol 3 days a week over 4 weeks from postnatal day (PND) 28 to PND 60, which included 10 mL/kg by oral gavage of distilled water, energy drink, caffeine (3.2 mg/kg), taurine (40 mg/kg), and their combinations with alcohol (2 g/kg). The animals were evaluated by behavioral tests from PND 56 to PND 60 (open field, plus maze and object recognition) and reproductive parameters (estrous cycle regularity, weight of sexual organs, oocyte quality, spermatid and sperm count, sperm morphology and testosterone level). Locomotor activity was increased in females in the groups combined with alcohol (except alcohol + caffeine) and in the caffeine group. Long-term memory was increased in males in the caffeine and taurine groups even when combined with alcohol. The combination of energy drinks and alcohol did not have significant effects on the reproductive parameters of either sex of rats during puberty. We concluded that energy drinks (and their main constituents) and alcohol combinations did not cause alterations in reproductive profiles, and locomotor activity and long-term memory were increased in females and males, respectively. • The locomotion in females was higher than males in open field test. • In males the memory is improved in caffeine and taurine groups. • Reproductive parameters didn't show difference in alcohol treated groups. • Caffeine and taurine in energy drinks can act as a protective substances. [ABSTRACT FROM AUTHOR]

Imidacloprid (IMI) is a neonicotinoid insecticide employed worldwide for crop protection. IMI's mode of action occurs through the agonism of postsynaptic nicotinic acetylcholine receptors (nAChRs), with high specificity for insect nAChRs although there are reports of mammals' toxicity. Studies on IMI's neurotoxicity are not conclusive; therefore, the aim of this study was to evaluate the subchronic toxic effects of an IMI based commercial pesticide on rats. Adult male Wistar rats received an IMI suspension via the oral route at doses of 1.5, 5, and 15 mg/kg for 45 consecutive days. IMI caused an increase in rearing and time spent at the periphery in the locomotor activity test and a decrease in time spent to finish the OX maze task (p < 0.05; ANOVA/Bonferroni). In blood, there was a decrease in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (p < 0.05; ANOVA/Bonferroni) and an increase in serum butyrylcholinesterase activity (p < 0.001; ANOVA/Bonferroni). Therefore, subchronic administration of an IMI-based-pesticide caused behavioral and systemic impairments in rats. • Imidacloprid increased rearing in rats. • Imidacloprid increased time spent at the periphery in the locomotor activity test. • Imidacloprid decreased the time spent to finish the OX maze task. • Imidacloprid decreased mean corpuscular hemoglobin in rats. • Imidacloprid increased serum butyrylcholinesterase in rats. [ABSTRACT FROM AUTHOR]

Exposure to ethanol alters the expression of brain-derived neurotrophic factor (BDNF) in central regions such as, the hippocampus, cortex and striatum. Moreover, chronic alcohol intake is known to induce selective neuronal damage associated with an increase in the inflammatory cascade, resulting in neuronal apoptosis and neurodegeneration. In the present study, we investigated the nociceptive response after 24 h of protracted alcohol abstinence. Rats were submitted to a model of alcohol withdrawal syndrome and the nociceptive response was assessed by the tail-flick and the hot plate tests. In addition, we evaluated BDNF and interleukin-10 (IL-10) in the cerebral prefrontal cortex, brainstem and hippocampus of rats after protracted alcohol abstinence. Male adult Wistar rats were divided into three groups: non-treated group (control group), treated with water (water group), and alcohol (alcohol group). The water and alcohol administrations were done by oral gavage and were performed over three periods of five days of treatment with two intervals of two days between them. Alcohol (20% w/v) was given at 4 g/kg of body weight. There was a significant effect of treatment in the tail-flick and hot plate latencies with greater latencies in alcohol-treated rats after 10 days of abstinence. There was a significant increase in the prefrontal cortex BDNF levels in the alcohol group in relation to the water group, after 11 days of alcohol abstinence. In addition, alcohol withdrawal induced a significant increase in the hippocampus, prefrontal cortex and brainstem IL-10 levels compared with control group. Thus, the present study demonstrates that protracted alcohol withdrawal produced an analgesic effect indexed via increased nociceptive threshold. We suggest that these effects could be related to the increased levels of BDNF and IL-10 observed in the central nervous system. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete combustion of organic material that is well known as a mutagenic and carcinogenic toxin. There are few studies addressing the molecular and cellular basis of behavioural alterations related to BaP exposure. The aim of this study was to evaluate the effect of subchronic oral administration of BaP on behavioral and neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity and short- and long-term memories were evaluated. Glial fibrillary acid protein and S100B content in the hippocampus, serum and CSF were measured using ELISA and total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named extracellular signal-regulated kinases 1 and 2, p38 and c-Jun amino-terminal kinases 1 and 2, in the hippocampus, were evaluated by western blotting. BaP induced a significant increase on locomotor activity and a decrease in short-term memory. S100B content was increased significantly in cerebrospinal fluid. BaP induced a decrease on ERK2 phosphorylation in the hippocampus. Thus, BaP subchronic treatment induces an astroglial response and impairs both motor and cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved in the hippocampal neuroplasticity. All these effects suggest that BaP neurotoxicity is a concern for environmental pollution. [ABSTRACT FROM AUTHOR]

1. The present work investigated the pharmacokinetic and tissue distribution as well as acute toxicity of a new chemical entity (NCE), the anticancer candidate LaSOM 65 in Wistar rats. 2. LaSOM 65 pharmacokinetics was investigated after intravenous (i.v., 1 mg/kg) and oral (p.o., 10 and 30 mg/kg) dosing. Tissue distribution was assessed after i.v. bolus dose. Acute toxicity was evaluated after i.v. (1, 2.5 and 5 mg/kg) and p.o. (50, 100 and 150 mg/kg) administration. 3. Short half-life (1.75 ± 0.71 h), a clearance of 0.85 ± 0.18 L/h/kg and a volume of distribution of 1.76 ± 0.24 L/kg were observed after i.v. dosing. The compound showed good bioavailability and linear pharmacokinetics after oral doses. The NCE distributes consistently in lung and fatty tissues, with penetration ratios of 2.7 and 1.4, respectively. The other tissues investigated presented smaller penetration ratios. Adverse clinical symptoms were observed only after i.v. administration, and regressed 3 h after dosing. Compared with controls, no statistical differences were found for serum analysis, body weight and relative organ weight, indicating no acute toxicological effects. 4. Overall, LaSOM 65 showed good pharmacokinetic characteristics and no signs of acute toxicity, indicating that it is a promising anticancer candidate. [ABSTRACT FROM AUTHOR]

Owing to concerns over the effects of the physicochemical properties of nanoparticles and their interaction with biological systems, further investigation is required. We investigated, for the first time, the toxicity of lipid-core nanocapsules (LNCs) containing a polymeric wall of poly(ɛ-caprolactone) and a coating of polysorbate 80 used as drug delivery devices (~245nm) in Wistar rats after single- and repeated-dose treatments. The suspensions were prepared by interfacial deposition of the polymer and were physicochemically characterized. Toxicological effects were determined after single doses of 18.03, 36.06, and 72.12 × 1012 LNC/kg and repeated doses of 6.01, 12.02, and 18.03 × 1012 LNC/kg for 28 days by ip administration. The results for both the treatments showed no mortality or permanent body weight changes during the experiments. A granulomatous foreign body reaction was observed in the liver and spleen of higher dose groups in acute and subchronic treatments. Most of the hepatotoxicity and nephrotoxicity markers were within the reference values and/or were similar to the control group. However, a slight alteration in the hematologic parameters was observed in both the studies. Thus, to verify a possible methodological influence, we performed an in vitro test to confirm such influence. These findings are in agreement with earlier reports regarding no appreciable toxicity of biodegradable polymeric nanoparticles, indicating that LNC might be a safe candidate for drug delivery system. Furthermore, the results presented in this study are important for health risk assessment and to implement strategies for testing biodegradable polymeric nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Passiflora alata is a Southern American species that constitutes many traditional remedies as well as phytomedicines used for sedative and anxiolytic purposes in Brazil. However studies on repeated treatment effects are scarce. Aim of the study: To evaluate behavioral, physiological and biochemical effects of the repeated treatment with an aqueous spray-dried extract of Passiflora alata leaves containing 2.5% (w/v) of flavonoids (PA) in mice. Material and methods: Male adult CF1 mice were treated (p.o.) for 14 days with PA (2.5; 25 or 250mg/kg). The feeding behavior was evaluated at the beginning (1h after the first administration) and at the end of the treatment (15th day). The body weight gain and food consumption were monitored along the days. On day 15 mice were evaluated on plus maze, spontaneous locomotor activity, catalepsy and barbiturate sleeping time tests. Serum glucose, lipids, ALT and AST enzymes were determined. Liver, kidney, perirenal fat, epididymal and peritoneal fat were analyzed. Results: The repeated treatment with the highest dose tested (250mg/kg) did not alter the mice behavior on open field, elevated plus maze, catalepsy and barbiturate sleeping time tests. Repeated administration of PA 250 decreased mice feeding behavior and weight gain. PA 25 and PA 250 reduced mice relative liver weight and caused mild hepatic hydropic degeneration as well as a decrease in alanine aminotransferase (ALT) serum level. Conclusions: These results indicate that Passiflora alata does not present central cumulative effects and point to the needs of further studies searching for its hepatotoxicity as well as potential anorexigenic. [Copyright &y& Elsevier]

p-Synephrine is an adrenergic amine found in Citrus aurantium L. fruits and has been used for weight loss in dietary supplements. There are commercial products containing this substance associated to caffeine, salicin, and ephedrine. The aim of this study was to evaluate the acute toxicity of this mixture in mice of both sexes. The significative results observed after acute oral administration to male and female mice of 300, 350, and 400 mg/kg total of p-synephrine, ephedrine, salicin, plus caffeine in a 10:4:6:80 w/w ratio included a reduction in locomotor activity and ptosis in all treated groups for both sexes. Seizures were also observed in male (400 mg/kg) and female groups (350 and 400 mg/kg). Gasping and tearing were observed in males. Salivation (400 mg/kg), agitation (350 and 400 mg/kg), and piloerection (all treated groups) were significantly observed only in females. Deaths occurred in males at 350 and 400 mg/kg treated groups and the necropsy showed cardiopulmonary hemorrhage. A reduction in locomotor activity was confirmed through the spontaneous locomotor activity test, in which the number of crossings considerably decreased (P < .01) in all treated groups. The rotarod test showed a decrease in motor coordination at 400 mg/kg. Body temperature decreased significantly (P < .01) in all treated groups compared to controls. The results suggested clear signs of toxicity of p-synephrine, ephedrine, salicin, and caffeine association; this toxicity augments the attentiveness on commercial products containing this mixture, given the expressive number of adverse events related to its utilization. [ABSTRACT FROM PUBLISHER]

Abstract: Extracts of Citrus aurantium L. (Rutaceae) unripe fruits have gained popularity for the treatment of obesity. Due to the wide use of C. aurantium/p-synephrine-containing products, this research was undertaken to evaluate its subchronic toxicity in mice and their actions in oxidative stress biomarkers. Groups of 9–10 mice received for 28 consecutive days a commercial C. aurantium dried extract (containing 7.5% p-synephrine) 400, 2000 or 4000mg/kg and p-synephrine 30 or 300mg/kg by oral gavage. There was a reduction in body weight gain of animals treated with both doses of p-synephrine. Organs relative weight, biochemical and hematological parameters were not altered in all treated mice. There was an increase in reduced glutathione (GSH) concentration in groups treated with C. aurantium 4000mg/kg and p-synephrine 30 and 300mg/kg. In glutathione peroxidase (GPx), there were an inhibition of the activity in C. aurantium 400 and 2000mg/kg and p-synephrine 30 and 300mg/kg treated animals, respectively, and was no alteration in malondialdehyde (MDA) levels. Thus, the results indicate a low subchronic toxicity of the tested materials in mice and a possible alteration in the oxidative metabolism. However, further tests are required to better elucidate the effects of these compounds in the antioxidant system. [Copyright &y& Elsevier]

Formulations containing Ephedra sinica Stapf. (Ephedraceae) and Citrus aurantium L. (Rutaceae) are consumed worldwide for body weight control. Considering the related adverse effects and the risk potential, the aim of this study is to evaluate the effects of the thermogenic compounds ephedrine, p-sinephrine, E. sinica and C. aurantium in the female reproductive system through the uterotrophic assay in immature female rats. The animals ( n = 6–7) received E. sinica 85.5 and 855.0 mg/kg/day, C. aurantium 25.0 and 50.0 mg/kg/day, ephedrine 5.0 mg/kg/day and p-synephrine 50.0 mg/kg/day for three consecutive days by oral gavage. For detection of antiestrogenicity, tamoxifen 20.0 mg/kg/day, E. sinica 855.0 mg/kg/day, C. aurantium 50.0 mg/kg/day, ephedrine 5.0 mg/kg/day and p-synephrine 50.0 mg/kg/day were administered to estrogen-treated females. Macroscopical alterations were evaluated in liver, kidneys, adrenals and uterus. All analyzed substances showed an antiestrogenic potential, but only ephedrine at 0.5 mg/kg/day presented a significative antiestrogenic effect ( P < 0.01). Adrenals relative mass were reduced ( P < 0.01) in all tested compounds when compared to the control, which seems to be related to the alfa-1-adrenoceptor agonist activity, which promote a vasoconstriction and reduction of the liquid in the organ. The endocrine system is highly complex and there are a number of ways in which a chemical may interfere with it, other in vivo and in vitro assays are being necessary to support this mechanism of action. [ABSTRACT FROM AUTHOR]

Abstract: The effect of methylprednisolone on the hydrolysis of adenine nucleotides by rat blood serum enzymes was studied. Adult male Wistar rats were submitted to three different treatments with synthetic steroid methylprednisolone: one dose of 50 mg/kg, i.p. (acute); or oral doses of 6 mg/kg dissolved in drinking water for 15 (sub-chronic) or 30 (chronic) days. Decreased ADP hydrolysis was observed after acute and sub-chronic treatments. Furthermore, ATP, ADP and AMP hydrolysis decreased after chronic treatment. These alterations may constitute one of the mechanisms that mediate the development of some of the side effects associated with corticosteroid use. [Copyright &y& Elsevier]

The possible reproductive adverse effects of the pesticide endosulfan on male offspring rats exposed in utero and during lactation were investigated. Dams were treated orally with 0, 0.5 or 1.5 mg of endosulfan/kg 21 days prior to mating, during the mating, pregnancy and lactation. Maternal and reproductive outcome data and male sexual development landmarks (testis descent and preputial separation) were assessed. Reproductive endpoints of the male offspring were examined at adulthood: sex organ weights, daily sperm production, spermatid number, sperm transit, sperm morphology and testosterone level. No signs of maternal toxicity were detected at the dose levels tested. Sexual development landmarks were also unaffected. Moreover, with the exception of a significant increase in the relative epididymis weight seen in the group treated with the lowest dose, we have not found any statistically significant adverse effect in the reproductive endpoints investigated at adulthood. The results of the present study indicate that pre and post-natal exposure to low doses of endosulfan (0.5 and 1.5 mg/kg) do not induce significant adverse effects in the reproductive system of male offspring Wistar rats at adulthood. [ABSTRACT FROM AUTHOR]

The use of the anthelmintic levamisole as a cocaine adulterant has been increasing worldwide. Complications caused by this association include systemic vasculitis, agranulocytosis, neutropenia, tissue necrosis, pulmonary hemorrhage, and renal injury. Data about toxicity of levamisole are scarce, therefore the aim of this study was to evaluate the acute and subchronic toxic effects of levamisole in rats. Male Wistar rats received saline or levamisole by intraperitoneal route at the doses of 12, 24 and 36 mg/kg in the acute toxicity test; and at 3, 6 and 12 mg/kg in the subchronic toxicity test. Toxicity was evaluated using behavioral, cognitive, renal, hematological, biochemical and histopathological parameters. Acute administration of levamisole caused behavioral and histopathological alterations. Subchronic administration caused behavioral, cognitive and hematological alterations (p < 0.0001 and p < 0.05, respectively), impairment of liver and kidney functions (p < 0.05), and changes of antioxidant defenses (p ≤ 0.0001). Both administrations produced toxic effects of clinical relevance, which make levamisole a dangerous cutting agent. Furthermore, the knowledge of these effects can contribute to the correct diagnosis and treatment of cocaine dependents with unusual systemic alterations. • The use of levamisole as a cocaine adulterant increased worldwide. • Several complications are associated with the concomitant use of these substances. • Data about the toxicology of levamisole are scarce. • Acute and subchronic administration of levamisole can cause toxic effects in rats. [ABSTRACT FROM AUTHOR]

• Curcumin 50 mg/kg had anxiolytic effects on the non-stressed animals. • Curcumin treatments prevented depressive-like behavior induced by CUMS. • Curcumin increased the catalase levels in the brains of the stressed animals. Curcumin has been investigated for the prevention and treatment of diseases due to its anti-oxidant, anti-inflammatory, immunomodulatory, and neuroprotective actions. This current study evaluated the adaptogenic effects of a subchronic oral administration of curcumin to Swiss mice that were submitted to a chronic unpredictable mild stress (CUMS) model of depression. Four groups of mice (vehicle control, CO; curcumin control, COC; CUMS + vehicle, CUMS; CUMS + curcumin, CUMSC) were evaluated for the biochemical parameters. The CUMS model caused depressive-like and anxiety-like behavior in the animals when they were viewed in the Forced Swimming Test and in the Elevated Plus Maze Test. The treatments with curcumin prevented the depressive-like behavior in the Forced Swimming Test and they had anxiolytic effects on the non-stressed animals. This was confirmed by the Elevated Plus Maze Test. Curcumin showed antioxidant effects (IC 50 of 38.86 ± 1.78 μg/mL) in the in vitro DPPH (2,2-diphenyl-1-picryl-hydrozole) test. The compound also showed antioxidant effects in vivo, increasing the catalase (CAT) levels in the brains of the stressed animals. The biochemical analyses did not reveal potential renal and hepatic damage. Together, these results have demonstrated the antidepressant and antioxidant effects of curcumin, highlighting in this mice model, the compound's novel adaptogenic potential. [ABSTRACT FROM AUTHOR]

• Biomarkers for insecticides are very important to monitoring occupational exposure. • Most of the existing biomarkers for pesticides are non-specific. • Higher prevalence of analyses involving OP insecticides classes. • The protective equipment used is still limited which can increase poisoning risk. Pesticides are widely used around the world, and rural workers have greater risk of poisoning. The use of biomarkers for insecticides can contribute to the diagnosis and prevention of poisoning. To identify, in the scientific literature, the biomarkers of occupational exposure to insecticides of different insecticide classes. The PubMed, Lilacs and Embase databases were analyzed using a systematic search strategy and in accordance with the criteria established by the PRISMA methodology. Articles with information related to the use of biomarkers to identify active ingredients, or insecticide metabolites, or effects on the human biological matrices were analyzed. A total of 840 studies was found, and 30 met the selection criteria. The search identified 118 results for insecticide biomarkers, of which 45% were of exposure, 42% of effect, and 14% of susceptibility. Additionally, 78 were possible biomarkers, and only 67 confirmed to be different biomarkers for insecticides. Acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 3,5,6-trichloro-2-pyridinol (TCP-y), specific for Chlorpyrifos, were among the most common biomarkers identified; however, most metabolites found were non-specific. Various insecticide biomarkers were mentioned; nonetheless, only a few are specific and used to identify the wide range of insecticides to which farm workers are exposed. [ABSTRACT FROM AUTHOR]