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Item Kolaviron suppresses dysfunctional reproductive axis associated with multi-walled carbon nanotubes exposure in male rats(Springer-Verlag GmbH, 2021) Adedara, I. A.; Awogbindin, I. O.; Maduako, I. C.; Ajeleti, A. O.; Owumi, S. E.; Owoeye, O.; Patlola, A. K.; Farombi, E. O.Reproductive toxicity associated with excessive exposure to multi-walled carbon nanotubes (MWCNTs), which are commonly used in medicine as valuable drug delivery systems, is well documented. Kolaviron, a bioflavonoid isolated from Garcinia kola seeds, elicits numerous health beneficial effects related to its anti-inflammatory, anti-genotoxic activities, anti-apoptotic, and antioxidant properties. However, information on the role of kolaviron inMWCNTs-induced reproductive toxicity is not available in the literature. Herein, we assessed the protective effects of kolaviron onMWCNTs-induced dysfunctional reproductive axis in rats following exposure toMWCNTs (1 mg/kg) and concurrent treatment with kolaviron (50 or 100 mg/kg body weight) for 15 successive days. Results showed thatMWCNTs-induced dysfunctional reproductive axis as evidenced by deficits in pituitary and testicular hormones, marker enzymes of testicular function, and sperm functional characteristics were abrogated in rats coadministered with kolaviron. Moreover, co-administration of kolaviron-abated MWCNTs-induced inhibition of antioxidant enzyme activities increases in oxidative stress and inflammatory indices. This is evidenced by diminished levels of tumor necrosis factor-alpha, nitric oxide, lipid peroxidation, reactive oxygen, and nitrogen species as well as reduced activity of myeloperoxidase in testes, epididymis, and hypothalamus of the rats. Biochemical data on the chemoprotection of MWCNTsinduced reproductive toxicity were corroborated by histological findings. Taken together, kolaviron suppressed dysfunctional reproductive axis associated with MWCNTs exposure via abrogation of oxidative stress and inflammation in male 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 Taurine enhances spermatogenic function and antioxidant defense mechanisms in testes and epididymis of L-NAME-induced hypertensive rats(Elsevier Masson SAS., 2018) Adedara, I. A.; Alake, S. E.; Adeyemo, M. O.; Olajide, L. O.; Ajibade, T. O.; Farombi, E. O.The beneficial health effects of taurine on hypertension have been demonstrated previously in both experimental and epidemiological studies. However, the role of taurine in reproductive dysfunction associated with hypertension has not been investigated. The present study evaluated the therapeutic efficacy of taurine on reproductive deficits in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Sixty male Wistar rats were randomly assigned into six groups namely control, taurine alone, L-NAME alone (40 mg/kg) or L-NAME treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for 28 consecutive days. Results indicated that taurine treatment significantly abrogated L-NAME-induced increase in systolic, diastolic and mean arterial pressures when compared with hypertensive control. Administration of taurine markedly increased antioxidant enzymes activities and glutathione level, whereas it suppressed the increase in biomarkers of oxidative stress in the testes and epididymis of L-NAME-induced hypertensive rats. Moreover, taurine significantly reversed hypertension mediated decreases in circulatory concentrations of luteinizing hormone, follicle- stimulating hormone and testosterone whereas it increased testicular sperm number, epididymal sperm number and sperm progressive motility in the hypertensive rats. Furthermore, taurine abrogated the suppression of marker enzymes of testicular function namely acid phosphatase, alkaline phosphatase and lactate dehydrogenase and preserved the histo-architectures of the testes and epididymis in L-NAME-induced hypertensive rats. Taken together, the findings from this study highlight the beneficial role of taurine in reproductive system of L-NAME-induced male hypertensive rats. Taurine supplementation may be a good clinical approach to prevent reproductive deficits in male hypertensive patients.Item Impact of prepubertal exposure to dietary protocatechuic acid on thè hypothalamic-pituitary-testicular axis in rats(Elsevier B.V., 2018) Adedara, I. A.; Omole, O.; Okpara, E. S.; Fasina, O. B.; Ayeni, M. F.; Ajayi, O. M.; Busari, E. O.; Farombi, E. O.Protocatechuic acid (PCA; 3, 4-dihydroxybenzoic acid) is a phenolic compound widely found in many edible fruits, vegetables, grape wine and plant-derived beverages. The present study investigated the impact of PCA on the hypothalamic-pituitary-testicular axis of rats orally treated with PCA during the period of prepubertal de- velopment to adulthood. Protocatechuic acid was administered to prepubertal male rats at doses of 0, 5, 10, 50 and 100mg/kg body for 45 consecutive days. The results revealed no treatment-related changes in the body weight gain and organo-somatic indices of the hypothalamus, testes, epididymis, prostate gland and seminal vesicle in rats administered with PCA when compared with control. However, prepubertal exposure to PCA significantly enhanced antioxidant enzyme activities and glutathione level whereas it markedly decreased bio- markers of inflammation and oxidative stress in the hypothalamus, testes and epididymis of the treated rats. Protocatechuic acid significantly increased circulatory concentrations of luteinizing hormone and follicle-sti- mulating hormone with concomitant increase in serum and intra-testicular testosterone levels. Moreover, PCA- treated rats exhibited significant increase in marker enzymes of testicular function namely acid phosphatase, alkaline phosphatase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase without statistically sig- nificant increase in spermatogenesis and sperm functional characteristics including sperm count, motility and viability. Light microscopic examination of the hypothalamus, testes and epididymis of rats treated with PCA showed histo-architectures similar to control. In conclusion, prepubertal exposure to PCA is safe and positively impacted reproductive function at sexual maturity in male rats. The observed beneficial effects of PCA is related to its anti-inflammatory and redox regulatory mechanisms.Item Redox status of the testes and sperm of rats following exposure to 2,5-hexanedione(Taylor & Francis Group, 2016) Adedara, I. A. || || || || ||; Abolaji, A. O.; Odion, B. E.; Omoloja, A. A.; Okwudi, I. J.; Farombi, E. O.Objectives: Exposure to 2, 5-hexanedione (2, 5-HD) is well known to be associated with reproductive dysfunctions in both humans and animals. However, the role of oxidative stress in 2, 5-HD-induced toxicity in testes and sperm has not yet been studied. Methodology: The present study investigated the influence of 2, 5-HD on antioxidant systems in the testes and epididymal sperm of rats following exposure to 0, 0.25, 0.5, and 1% 2, 5-HD in drinking water for 21 consecutive days. Results: Administration of 0.5% 2, 5-HD significantly (P < 0.05) decreased epididymis weight, whereas 1% 2, 5-HD-treated rats showed significantly decreased body weight, testis, and epididymis weights compared with the control group. Exposure to 2, 5-HD caused a significant dose-dependent increase in the activities of superoxide dismutase, catalase, and glutathione peroxidase in both testes and sperm compared with the control group. Moreover, 2, 5-HD-exposed rats showed significant decrease in glutathione-S-transferase activity and glutathione level with concomitant significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm. Testicular and epididymal atrophy with significant, dose-dependent, decrease in epididymal sperm number, sperm motility, and viability were observed in 2, 5-HD-treated rats. Conclusion: 2,5-HD exposure impaired testicular function and sperm characteristics by disruption of the antioxidant systems and consequently, increased oxidative stress in the treated rats.Item Kolaviron protects against benzo[a]pyrene-induced functional alterations along the brain-pituitary-gonadal axis in male rats(Elsevier B.V., 2015) Adedara, I. A.; Owoeye, O.; Aiyegbusi, O.; Dagunduro, J. O.; Daramola, Y. M.; Farombi, E. O.Exposure to benzo[a]pyrene (B[a]P) is well reported to be associated with neurological and reproductive dysfunctions. The present study investigated the influence of kolaviron, an isolated biflavonoid from the seed of Garcinia kola, on functional alterations along the brain-pituitary-gonadal axis in male rats exposed to B[a] P. Benzo[a]pyrene was orally administered at a dose of 10 mg/kg alone or orally co-administered with kolaviron at 100 and 200 mg/kg for 15 consecutive days. Administration of B[a]P significantly (p < 0.05) decreased plasma levels of pituitary hormones namely follicle-stimulating hormone (FSH) and prolactin but increased luteinizing hormone (LH) by 47%, 55% and 20.9%, respectively, when compared with the control. The significant decrease in gonadosomatic index (GSI) was accompanied by significant decrease in testosterone production and sperm functional parameters in the B[a]P- treated rats. Moreover, B[a]P - treated rats showed significant elevation in the circulatory concentrations of pro-inflammatory cytokines and oxidative stress indices in the brain, testes and sperm of B[a]P-treated rats. Light microscopy revealed severe necrosis of the Purkinje cells in the cerebellum, neuronal degeneration of the cerebral cortex, neuronal necrosis of the hippocampus and testicular atrophy in B[a]P-treated rats. Kolaviron co-treatment significantly ameliorated B[a]P mediated damages by suppressing pro-inflammatory mediators and enhancing the antioxidant status, neuroendocrine function, sperm characteristics and improving the architecture of the brain and testes in B[a]P-treated rats. The findings in the present investigation highlight that kolaviron may be developed to novel therapeutic agent against toxicity resulting from B[a]P exposure.Item Sperm functional parameters and erythrocytes oxidant–antioxidant imbalance during municipal landfill leachate treatment withdrawal in rats(Elsevier B.V., 2014) Adedara, I. A.; Lawal, T. A.; Adesina, A. A.; Oyebiyi, O. O.; Ebokaiwe, A. P.; Farombi, E. O.Adequate information on how leachates affect hematological and reproductive functions is necessary to help in linking causality with predictable response. The present study investigated the effects of Olushosun municipal landfill leachate (OMLL) exposure and withdrawal on sperm characteristics and erythrocytes oxidant–antioxidant balance in rats. Adult male Wistar rats were exposed to 0%, 12.5% and 25% OMLL in drinking water for 28 days. One half of the rats in each group were sacrificed on day 29 while the remaining one-half stayed an additional 28 days without treatment. OMLL exposure significantly decreased sperm functional parameters, disrupted antioxidant systems with concomitant elevation in hydrogen peroxide and malondial dehyde levels in erythrocytes and sperm. Following withdrawal of treatment, OMLL-mediated decrease in sperm count and daily sperm production were reversed to near control. However, erythrocytes and sperm oxidative damage, increased sperm abnormalities, decreased epididymis weight, sperm progressive motility and testicular sperm number persisted and were consistent with results obtained from rats sacrificed immediately after OMLL treatment. Collectively, OMLL-induced irreversible oxidative damage to erythrocytes and sperm in rats within the time course of investigation. These findings highlight potential adverse effects of OMLL on individuals unduly exposed to leachates contaminated substances.Item Aflatoxin B1 disrupts the androgen biosynthetic pathway in rat Leydig cells(Elsevier Ltd., 2014) Adedara, I. A.; Nanjappa, M. K.; Farombi, E. O.; Akingbemi, B. T.The present study investigated if Aflatoxin B1 (AFB1), a potent and naturally occurring mycotoxin, interferes with the steroidogenic pathway in rat Leydig cells. Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone (T) that maintains the male phenotype and support fertility. Leydig cells, isolated from 35-day-old male Long-Evans rats (Rattus norvegicus), were incubated with AFB1 at 0, 0.01, 0.1, 1, 10 lM followed by measurement of T secretion by radioimmunoassay and analysis of protein expression in western blots. Results demonstrated that AFB1 suppressed testosterone secretion in a dose-dependent manner and inhibited expression of cholesterol transporter steroidogenic acute regulatory protein (StAR) and steroidogenic enzymes [(3b-hydroxysteroid dehydrogenase (3b-HSD) and 17b-hydroxysteroid dehydrogenase enzyme (HSD17B3)]. Protein expression analysis showed that AFB1 treatment increased ERK phosphorylation but suppressed p38 MAPK and JNK activation in Leydig cells. AFB1-induced inhibition of Leydig cells was alleviated by co-treatment with the ERK inhibitor UO 126, implying that ERK mediates, at least in part, the inhibitory effects of AFB1 in Leydig cells. The findings highlight potential extra-hepatic effects of aflatoxin exposure and indicate that exposure to AFB1 has significant reproductive health implications for consumers of contaminated products even under conditions of low dietary toxin levels.Item Possible ameliorative effects of kolaviron against reproductive toxicity in sub-lethally whole body gamma-irradiated rats(Elsevier GmbH., 2010) Adaramoye, O. A.; Adedara, I. A.; Farombi, E. O.Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body _-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of _-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to _-radiation. Gamma-irradiation resulted in a significant (p < 0.05) decrease in body weight and relative testes weight. Also, _-irradiation significantly (p < 0.05) decreased the activities of superoxide dismutase, catalase and glutathione S-transferase as well as glutathione level, but markedly elevated malondialdehyde levels in the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (p < 0.05) decreased the body weight loss and increased relative testes weights of the rats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together,_-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity.