FACULTY OF BASIC MEDICAL SCIENCES
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Item Neuroprotective mechanisms of selenium against arsenic-induced behavioral impairments in rats(Elsevier B.V., 2020) Adedara, I. A.; Fabunmi, A. T.; Ayenitaju, A. C.; Atanda, O. E.; Adebowale, A. A.; Ajayi, B. O.; Rocha, J. B. T.; Owoeye, O.; Farombi, E. O.Environmental pollution due to arsenic is associated with several adverse health effects including neurotoxicity in animals and humans. Selenium is a nutritionally essential trace metalloid well documented to elicit com- pelling pharmacological activities in vitro and in vivo. Report on the influence of selenium on arsenic-mediated behavioral derangement is lacking in literature. Hence, to fill this knowledge gap, rats were either exposed to arsenic per se in drinking water at 60 pg AsO2Na/L or co-administered with inorganic selenium at 0.25 mg/kg or organic selenium diphenyl diselenide (DPDS) at 2.5 mg/kg body weight for 45 successive days. Neurobehavioural data from rats in a new environment using video-tracking software evinced that inorganic and organic forms of selenium significantly (p < 0.05) abrogated arsenic-induced motor and locomotor in- sufficiencies such as increased negative geotaxis and fecal pellets numbers as well as the diminution in grip strength, body rotation, maximum speed, absolute turn angle and total distance travelled. The augmentation in the behavioral activities in rats co-administered with arsenic and both forms of selenium was substantiated using track and occupancy plots analyses. Selenium mitigated arsenic-induced decreases in glutathione level and acetylcholinesterase activity as well as the increase in oxidative stress and reactive oxygen and nitrogen species. Moreover, selenium diminished inflammatory parameters (myeloperoxidase activity, nitric oxide, tumour ne- crosis factor alpha and interleukin-1 beta levels), caspase-3 activity and ameliorated histological lesions in the cerebellum, cerebrum and liver of the rats. Collectively, selenium abated arsenic-induced behavioral derange- ments via anti-inflammation, antioxidant and anti-apoptotic mechanisms in rats.Item Selenium abates reproductive dysfunction via attenuation of biometal accumulation, oxido-inflammatory stress and caspase-3 activation in male rats exposed to arsenic(Elsevier Ltd., 2019) Adedara, I. A.; Adebowale, A. A.; Atanda, O. E.; Fabunmi, A. T.; Ayenitaju, A. C.; Rocha, J. B. T.; Farombi, E. O.Frequent exposure to arsenic is well documented to impair reproductive function in humans and animals. Biological significance of inorganic selenium and organoselenium, diphenyl selenide (DPDS), has been attributed to their pharmacological activities. However, their roles in arsenic-mediated reproductive toxicity is lacking in literature. The present study evaluated the protective effects elicited by selenium and DPDS in arsenic-induced reproductive deficits in rats. Animals were either exposed to arsenic alone in drinking water at 60 µg AsO₂Na L⁻¹ or co-treated with selenium at 0.25 mg kg⁻¹ or DPDS at 2.5 mg kg⁻¹ body weight for 45 consecutive days. Results indicated that arsenic-mediated deficits in spermatogenic indices and marker enzymes of testicular function were significantly abrogated in rats co-treated with selenium or DPDS. Additionally, selenium or DPDS co-treatment prevented arsenic-mediated elevation in oxidative stress indices and significantly suppressed arsenic-mediated inflammation evidenced by diminished myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha, interleukin-1 beta levels in hypothalamus, testes and epididymis of the rats. Moreover, selenium or DPDS abrogated arsenic mediated activation of caspase-3 activity and histological lesions in the treated rats. Taken together, selenium or DPDS improved reproductive function in arsenic-exposed rats via suppression of inflammation, oxidative stress and caspase-3 activation in rats.Item Suppression of the brain-pituitary-testicular axis function following acute arsenic and manganese co-exposure and withdrawal in rats(Elsevier GmbH., 2017) Adedara, I. A.; Abolaji, A. O.; Awogbindin, I. O.; Farombi, E. O.Despite the fact that most environmental exposures to metals do not occur in isolation, the combined effects of metal mixtures on brain–pituitary–gonadal axis are poorly known. The present study investigated the impacts of co-exposure to arsenic (As) and manganese (Mn) on sperm characteristics, reproductive hormones and selected oxidative stress indices in the brain, testes and epididymis of rats following exposure for 15 consecutive days to 60 mg/L of AsO₃Na and 30 mg/L of MnCl₂ in drinking water. The results showed that while brain weight remained unaffected, the fluid intake and the weights of testes and epididymis significantly (p < 0.05) decreased in all the treatment groups. A significant decrease in the body weight gain when compared with control was noted only in the co-exposed rats. Moreover, the significant decreases in the antioxidant status in brain, testes and epididymis as well as in the circulatory concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone were similar following separate or combined exposure of rats to As and Mn. The marked oxidative damage in the investigated tissues was accompanied by a significant decrease in the sperm quantity and quality in all the treated rats when compared with the control. Interestingly, most of the parameters determined immediately after the exposure period persisted in rats from the withdrawal experiment. Collectively, co-exposure to As and Mn suppressed the brain–pituitary–testicular axis function and the post-testicular events such as sperm function possibly via a mechanism involving persistent oxidative stress and endocrine disruption in the exposed rats.Item Endocrine disruptors-arsenic, cadmium and lead in pre and postmenopausal black women with breast cancer(University College Hospital, Ibadan, 2017) Ajayi, O. O.; Charles-Davies, M. A.; Anetor, J. I.; Ademola, A. F.Background: The involvement of toxic metals in adiposity has been suggested to be contributory to the high incidence of breast cancer, particularly in sub-Saharan Africa. This study is aimed at evaluating serum arsenic, cadmium and lead in relation to adiposity and blood pressure in Nigerian women with breast cancer. Methodology: The study comprised 85 women newly diagnosed with breast cancer pre-therapy (cases) matched with 84 apparently healthy women without breast cancer (controls) according to age and menstrual phase. Arsenic (As), cadmium (Cd) and Lead (Pb) levels were determined by atomic absorption spectrophotometry. Blood pressure and anthropometry were determined by standard methods. Data analysed by Student’s t-test and Pearson correlation coefficient were considered statistically significant at p<0.05. Results: Cd and Pb levels were significantly higher in cases, compared with controls (p<0.05). Waist circumference (WC), hip circumference (HC), weight, height, waist hip ratio (WHR), waist height ratio (WHtR) were significantly higher in cases compared with controls (p<0.05). Cadmium positively correlated with diastolic blood pressure while FT4 inversely correlated with arsenic in the cases (p<0.05). Conclusion: Observations in this study suggest the involvement of these toxic metals in adiposity which could be involved in breast carcinogenesis.