Diphenyl Diselenide Through Reduction of Inflammation, Oxidative Injury and Caspase-3 Activation Abates Doxorubicin-Induced Neurotoxicity in Rats.

Neurotoxicity associated with chemotherapy is a debilitating side effect of cancer management in humans which reportedly involves inflammatory and oxidative stress responses. Diphenyl diselenide (DPDS) is an organoselenium compound which exhibits its anti-tumoral, anti-oxidant, anti-inflammatory and anti-mutagenic effects. Nevertheless, its possible effect on chemotherapy-induced neurotoxicity is not known. Using rat model, we probed the behavioral and biochemical effects accompanying administration of antineoplastic agent doxorubicin (7.5 mg/kg) and DPDS (5 and 10 mg/kg). Anxiogenic-like behavior, motor and locomotor insufficiencies associated with doxorubicin were considerably abated by both DPDS doses with concomitant enhancement in exploratory behavior as demonstrated by reduced heat maps intensity and enhanced track plot densities. Moreover, with exception of cerebral glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, biochemical data demonstrated reversal of doxorubicin-mediated decline in cerebral and cerebellar antioxidant status indices and the increase in acetylcholinesterase (AChE) activity by both doses of DPDS. Also, cerebellar and cerebral lipid peroxidation, hydrogen peroxide as well as reactive oxygen and nitrogen species levels were considerably diminished in rats administered doxorubicin and DPDS. In addition, DPDS administration abated myeloperoxidase activity, tumour necrosis factor alpha and nitric oxide levels along with caspase-3 activity in doxorubicin-administered rats. Chemoprotection of doxorubicin-associated neurotoxicity by DPDS was further validated by histomorphometry and histochemical staining. Taken together, DPDS through offsetting of oxido-inflammatory stress and caspase-3 activation elicited neuroprotection in doxorubicin-treated rats.

Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles.

The broad contemporary applications of silver nanoparticles (AgNPs) have been associated with various toxicities including reproductive toxicity. Taurine is well acknowledged for its potent pharmacological role in numerous disease models and chemically-mediated toxicity. We investigated the effect of taurine on AgNPs-induced reproductive toxicity in male rats. The animals were intraperitoneally injected with AgNPs (200 µg/kg) alone or co-administered with taurine at 50 and 100 mg/kg for 21 successive days. Exogenous taurine administration significantly abated AgNPs-induced oxidative injury by decreasing the levels of oxidative stress indices while boosting antioxidant enzymes activities and glutathione level in the hypothalamus, testes and epididymis of exposed animals. Taurine administration alleviated AgNPs-induced inflammatory response and caspase-3 activity, an apoptotic biomarker. Moreover, taurine significantly improved spermiogram, reproductive hormones and the marker enzymes of testicular function in AgNPs-treated animals. The ameliorative effect of taurine on pathological lesions induced by AgNPs in the exposed animals was substantiated by histopathological data. This study provides the first mechanistic evidence that taurine supplementation affords therapeutic effect against reproductive dysfunction associated with AgNPs exposure in male rats.

Perfluorooctanoic acid induces behavioral impairment and oxidative injury in Nauphoeta cinerea nymphs.

Perfluorooctanoic acid (PFOA) is a persistent organic contaminant with potential health threats to both animals and humans. However, the impact of PFOA on insects, which play significant roles in ecosystems, is understudied. We evaluated the toxicological impact of ecologically relevant concentrations of PFOA (0, 25, 50, 100, and 200 µg L-1) on Nauphoeta cinerea nymphs following exposure for 42 consecutive days. We analyzed the behavior of the insects with automated video-tracking software and processed the head, midgut, and fat body for biochemical assays. PFOA-exposed insects exhibited significant reductions in locomotory abilities and an increase in freezing time. Furthermore, PFOA exposure reduced acetylcholinesterase activity in the insect head. PFOA exposure increased the activities of superoxide dismutase, glutathione peroxidase, and catalase in the head and midgut, but decreased them in the fat body. PFOA also significantly increased glutathione-S transferase activity, while decreasing glutathione levels in the head, midgut, and fat body. Additionally, PFOA exposure increased reactive oxygen and nitrogen species, nitric oxide, lipid peroxidation, and protein carbonyl contents in the head, midgut, and fat body of the insects. In conclusion, our findings indicate that PFOA exposure poses an ecological risk to Nauphoeta cinerea.

Atrazine: cytotoxicity, oxidative stress, apoptosis, testicular effects and chemopreventive Interventions.

Atrazine (ATZ) is an environmental pollutant that interferes with several aspects of mammalian cellular processes including germ cell development, immunological, reproductive and neurological functions. At the level of human exposure, ATZ reduces sperm count and contribute to infertility in men. ATZ also induces morphological changes similar to apoptosis and initiates mitochondria-dependent cell death in several experimental models. When in vitro experimental models are exposed to ATZ, they are faced with increased levels of reactive oxygen species (ROS), cytotoxicity and decreased growth rate at dosages that may vary with cell types. This results in differing cytotoxic responses that are influenced by the nature of target cells, assay types and concentrations of ATZ. However, oxidative stress could play salient role in the observed cellular and genetic toxicity and apoptosis-like effects which could be abrogated by antioxidant vitamins and flavonoids, including vitamin E, quercetin, kolaviron, myricetin and bioactive extractives with antioxidant effects. This review focuses on the differential responses of cell types to ATZ toxicity, testicular effects of ATZ in both in vitro and in vivo models and chemopreventive strategies, so as to highlight the current state of the art on the toxicological outcomes of ATZ exposure in several experimental model systems.

Metoprolol elicits neurobehavioral insufficiency and oxidative damage in nontarget Nauphoeta cinerea nymphs.

Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 µg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video-tracking software (ANY-maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol-exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol-mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol-exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido-inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects.

Neurotoxicity of furan in juvenile Wistar rats involves behavioral defects, microgliosis, astrogliosis and oxidative stress.

Evidence suggests that furan, a widespread environmental and food contaminant, causes liver toxicity and cancer, but its implications in the brain are not well defined. We measured behavioral, glial, and biochemical responses in male juvenile rats exposed orally to 2.5, 5 and 10 mg/kg furan and vitamin E after 28 days. Furan-mediated hyperactivity peaked at 5 mg/kg and did not exacerbate at 10 mg/kg. Enhanced motor defect was also observed at 10 mg/kg. Furan-treated rats elicited inquisitive exploration but showed impaired spatial working memory. Without compromising the blood-brain barrier, furan induced glial reactivity with enhanced phagocytic activity, characterized by parenchyma-wide microglial aggregation and proliferation, which switched from hyper-ramified to rod-like morphology with increasing doses. Furan altered the glutathione-S-transferase-driven enzymatic and non-enzymatic antioxidant defence systems differentially and dose-dependently across brain regions. Redox homeostasis was most perturbed in the striatum and least disrupted in hippocampus/cerebellum. Vitamin E supplementation attenuated exploratory hyperactivity and glial reactivity but did not affect impaired working memory and oxidative imbalance. Overall, sub-chronic exposure of juvenile rats to furan triggered glial reactivity and behavioral deficits suggesting the brain's vulnerability during juvenile development to furan toxicity. It remains to be determined whether environmentally relevant furan concentrations interfere with critical brain developmental milestones.

Amelioration of neurobehavioral, biochemical, and morphological alterations associated with silver nanoparticles exposure by taurine in rats.

The adverse effect of silver nanoparticles (AgNPs) on the nervous system is an emerging concern of public interest globally. Taurine, an essential amino acid required for neurogenesis in the nervous system, is well-documented to possess antioxidant, anti-inflammatory, and antiapoptotic activities. Yet, there is no report in the literature on the effect of taurine on neurotoxicity related to AgNPs exposure. Here, we investigated the neurobehavioral and biochemical responses associated with coexposure to AgNPs (200 µg/kg body weight) and taurine (50 and 100 mg/kg body weight) in rats. Locomotor incompetence, motor deficits, and anxiogenic-like behavior induced by AgNPs were significantly alleviated by both doses of taurine. Taurine administration enhanced exploratory behavior typified by increased track plot densities with diminished heat maps intensity in AgNPs-treated rats. Biochemical data indicated that the reduction in cerebral and cerebellar acetylcholinesterase activity, antioxidant enzyme activities, and glutathione level by AgNPs treatment were markedly upturned by both doses of taurine. The significant abatement in cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, hydrogen peroxide, and lipid peroxidation was evident in rats cotreated with AgNPs and taurine. Further, taurine administration abated nitric oxide and tumor necrosis factor-alpha levels cum myeloperoxidase and caspase-3 activities in AgNPs-treated rats. Amelioration of AgNPs-induced neurotoxicity by taurine was confirmed by histochemical staining and histomorphometry. In conclusion, taurine via attenuation of oxido-inflammatory stress and caspase-3 activation protected against neurotoxicity induced by AgNPs in rats.

Attenuation of doxorubicin-induced hypothalamic-pituitary-testicular axis dysfunction by diphenyl diselenide involves suppression of hormonal deficits, oxido-inflammatory stress and caspase 3 activity in rats.

BACKGROUND: Doxorubicin (DOX) is one of the popular anti-cancer drugs in the world and several literatures have implicated it in various toxicities especially cardiotoxicity and reproductive toxicity. Diphenyl diselenide (DPDS) is well acknowledged for its compelling pharmacological effects in numerous disease models and chemically-mediated toxicity. This study was carried out to investigate the effect of DPDS on DOX-induced changes in the reproductive indices of male Wistar rats. METHODS: Rats were intraperitoneally injected with 7.5 mg/kg body weight of DOX alone once followed by treatment with DPDS at 5 and 10 mg/kg for seven successive days. Excised hypothalamus, testes and epididymis were processed for biochemical and histological analyses. RESULTS: DPDS treatment significantly (p < 0.05) abated DOX-induced oxidative damage by decreasing the levels of oxidative stress indices such as hydrogen peroxide, reactive oxygen and nitrogen species, and lipid peroxidation with a respective improvement in the level of glutathione in the hypothalamic, testicular and epididymal tissues of DOX-treated rats. The activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione S-transferase and glutathione peroxidase were upregulated in the DPDS co-treated group. DPDS co-treatment alleviates the burden of DOX-induced inflammation by significant reductions in myeloperoxidase activity, levels of nitric oxide and tumor necrosis factor alpha with concomitant decline in the activity of caspase-3, an apoptotic biomarker. Consequently, significant improvement in the spermiogram, levels of reproductive hormones (follicle stimulating hormone, luteinizing hormone, prolactin, serum testosterone and intra-testicular testosterone) levels in the DPDS co-treatment group in comparison to DOX alone-treated group were observed. Histology results of the testes and epididymis showed that DPDS significantly alleviated pathological lesions induced by DOX in the animals. CONCLUSION: DPDS may modulate reproductive toxicity associated with DOX therapy in male cancer patients.

Dietary myricetin assuages atrazine-mediated hypothalamic-pituitary-testicular axis dysfunction in rats.

Atrazine (ATZ) exposure is associated with reproductive dysfunction in both animals and humans. Myricetin, a flavonoid compound, is well documented for its numerous pharmacological activities. However, the impact of myricetin on the atrazine-mediated dysfunctional hypothalamic-pituitary-testicular axis is not known. This study investigated the role of myricetin on the atrazine-induced alterations in the male reproductive axis in rats orally gavaged with ATZ alone (50 mg/kg) or co-treated with ATZ + myricetin (MYR) at 5, 10, and 20 mg/kg for 30 consecutive days. Myricetin assuaged ATZ-induced reductions in intra-testicular testosterone, serum follicle-stimulating hormone, luteinizing hormone, and testosterone, coupled with decreases in alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activities. Also, MYR treatment improved epididymal sperm count and motility and decreased sperm defects in ATZ-treated rats. Testicular sperm number, daily sperm production, and sperm viability remained unchanged in all treatment groups. Administration of MYR abated ATZ-mediated depletion in antioxidant status, an increase in myeloperoxidase activity, nitric oxide, hydrogen peroxide, malondialdehyde levels, and reactive oxygen and nitrogen species, as well as the histological lesions in the hypothalamus, epididymis, and testes of treated animals. All in all, MYR mitigated atrazine-mediated functional changes in the reproductive axis via anti-inflammatory and antioxidant mechanisms in atrazine-exposed rats. Dietary intake of MYR could be a worthy chemoprotective approach against reproductive dysfunction related to ATZ exposure.