Biochemistry
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Item Taurine Ameliorates Thyroid Hypofunction and renal injury in L-NAME-Induced hypertensive rats(Georg Thieme Verlag KG Stuttgart, 2018) Adedara, I. A. || || || || ||; Alake, S. E.; Olajide, L. O.; Adeyemo, M. O.; Ajibade, T. O.; Farombi, E. O.There is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, LNAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.Item Acute diethyl nitrosamine and cadmium co‐exposure exacerbates deficits in endocrine balance, sperm characteristics and antioxidant defence mechanisms in testes of pubertal rats(Blackwell Verlag GmbH, 2019) Owumi, S. E.; Adedara, I. A.; Duro-Ladipo, A.; Farombi, E. O.Diethylnitrosamine (DEN) and cadmium are environmental contaminants of known poisonous consequences in animals and humans. We examined the influence of acute oral co‐exposure to DEN (10 mg/kg) and cadmium (5 mg/kg) on endocrine balance, semen and antioxidant status in rat testes. The results indicated decreases (p < 0.05) in the weight of the testis and organo‐somatic index of the testes in rats administered with either DEN or cadmium were aggravated in the co‐exposed rats. Serum concentrations of follicle‐stimulating hormone (FSH), luteinising hormone (LH) and testosterone decreased, and were more pronounced in rats co‐treated with DEN and cadmium. Enzymatic and non-enzymatic antioxidant activities decreased following separate exposure to DEN and cadmium, and were increased in rats co‐treated with DEN and cadmium. The significant (p < 0.05) increases in malondialdehyde (MDA) was complemented by marked increase in sperm abnormalities, reduction in the sperm count, motility and viability compared with control. Histologically, co‐exposure to DEN and cadmium aggravates their discrete effects on the testes. Co‐exposure to DEN and cadmium elicited more severe endocrine disruption and testicular oxidative damage in rats, revealing additive adverse effects on testicular functions in rats and as such, may put exposed individual at greater risk.Item Responses of testis, epididymis, and sperm of pubertal rats exposed to functionalized Multiwalled Carbon Nanotubes(Wiley Periodicals, Inc., 2014) Farombi, E. O.; Adedara, I. A.; Forcados, G. E.; Anao, O. O.; Agbowo, A.; Patlola, A. K.The present study investigated the response of testes, epididymides and sperm in pubertal Wistar rats following exposure to 0, 0.25, 0.5, 0.75, and 1.0 mg kg21 functionalized multi-walled carbon nanotubes (f-MWCNTs) for 5 days. The results showed that administration of (f-MWCNTs) significantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in a dose dependent manner in both testes and sperm compared with control group. Moreover, the significant decrease in the activity of glutathione-S-transferase and glutathione level was accompanied with significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm of (f- MWCNTs)-treated rats. The spermiogram of (f-MWCNTs)-treated rats indicated significant decrease in epididymal sperm number, sperm progressive motility, testicular sperm number and daily sperm production with elevated sperm abnormalities when compared with the control. Exposure to (f-MWCNTs) decreased plasma testosterone level and produced marked morphological changes including decreased geminal epithelium, edema, congestion, reduced spermatogenic cells and focal areas of tubular degeneration in the testes. The lumen of the epididymides contained reduced sperm cells and there was mild to severe hyperplasia epithelial cells lining the duct of the epididymis. Collectively, pubertal exposure of male rats to (f-MWCNTs) elicited oxidative stress response resulting in marked testicular and epididymides dysfunction.Item 6-Gingerol-Rich fraction from Zingiber officinale prevents hematotoxicity and oxidative damage in kidney and liver of rats exposed to Carbendazim(Taylor & Francis Group, LLC, 2016) Salihu, M.; Ajayi, B. O.; Adedara, I. A.; Farombi, E. O.Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6-GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats co-treated with 6-GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats.Item Kolaviron and vitamin E ameliorate hematotoxicity and oxidative stress in brains of prepubertal rats treated with an anticonvulsant phenytoin(Informa Healthcare USA, 2014) Owoeye, O.; Adedara, I. A.; Bakare, O. S.; Adeyemo, O. A.; Egun, C.; Farombi, E. O.Phenytoin (PHT), an anticonvulsant agent, widely used for the treatment of epilepsy has been reported to exhibit toxic side effects. The present study investigated the protective effects of kolaviron and vitamin E on hematotoxicity and neurotoxicity induced by phenytoin, in prepubertal male rats. The animals were treated with PHT (75 mg/kg) separately or in combination with either kolaviron (200 mg/kg) or vitamin E (500 mg/kg) for 14 days. Phenytoin treatment significantly decreased the hemoglobin, white blood cells, lymphocytes and mean corpuscular volume levels without affecting red blood cell, packed cell volume, neutrophils, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration when compared with the control rats. There was a significant increase in lipid peroxidation and hydrogen peroxide levels with marked depletion in antioxidant status in brains of PHT-treated rats when compared with the control. Although PHT treatment had no effect on the granular layer, widest diameter of Purkinje cells and Purkinje layer of the cerebellum, it significantly reduced its molecular layer and the density of Purkinje cell. Administration of PHT significantly reduced the densities of the granule cells of the dentate gyrus and the pyramidal neurons of the cornu ammonis of hippocampus proper. Co-treatment with kolaviron and vitamin E effectively reversed the PHT-mediated alterations in the hematology, brain antioxidant status and histomorphometry when compared to PHT only. Taken together, the present data indicate the abilities of kolaviron and vitamin E to ameliorate phenytoin-induced hematotoxicity and oxidative stress in brains of rats.Item Sperm characteristics, antioxidant status and hormonal profile in rats treated with artemisinin(Blackwell Verlag GmbH, 2013) Farombi, E. O.; Adedara, I. A.; Abolaji, A. O.; Anamelechi, J. P.; Sangodele, J. O.The indiscriminate use, abuse and patients’ noncompliance to normal prescription of artemisinin and its derivatives are a common practice during the treatment for drug-resistant malaria parasites in most developing countries. This study investigated the influence of artemisinin on the testicular and epididymal sperm antioxidant systems as well as on the plasma levels of hormones from the pituitary and thyroid components of the brain–pituitary–testicular axis. Oral exposure of rats to 0, 7 and 35 mg kg_1 artemisinin for 7 days showed that the testicular antioxidant status at both therapeutic dose (7 mg kg_1) and overdose (35 mg kg_1), and the sperm antioxidant status at therapeutic dose of artemisinin remained unaffected compared with control. However, increased hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant decrease in glutathione peroxidase and glutathione-S-transferase activities as well as glutathione level in spermatozoon of rats administered with overdose of artemisinin. While plasma levels of all the hormones investigated remained unaffected, severe epididymal degeneration with concomitant decrease in sperm quantity and quality was observed in rats treated with overdose of artemisinin compared with control. Overall, induction of oxidative stress in the epididymis, but not in the testes, could cause reproductive deficits in individuals unduly undergoing artemisinin therapy.Item Kolaviron prevents ethylene glycol monoethyl ether-induced testicular apoptosis via down-regulation of stress proteins, Fas/Fas-L and caspases expressions in rats(Informa Healthcare USA, Inc., 2013) Adedara, I. A.; Mathur, P. P.; Farombi, E. O.This study investigated the protective role of kolaviron, a natural antioxidant biflavonoid isolated from the seed of Garcinia kola, in ethylene glycol monoethyl ether (EGEE)-induced testicular dysfunction in male rats. Adult male Wistar rats were exposed to EGEE (200 mg/kg) separately or in combination with either kolaviron (100 or 200 mg/kg) or vitamin E (50 mg/kg) for 14 days. Immunoblot analysis revealed that EGEE exposure alone significantly increased stress-inducible proteins levels. The increased protein expression of active caspases, Fas and Fas-L, was accompanied by nuclear factor kappa B downregulation and elevation of cytosolic cytochrome c level in EGEE-treated rats. In addition, the observation from immunofluorescence staining was consistent with the increased TUNEL-positive nuclei in the testes of EGEE-treated rats. Kolaviron and vitamin E significantly inhibited induction of stress proteins and germ cell apoptosis in EGEE-treated rats. Overall, kolaviron by virtue of its antioxidant and anti-apoptotic properties prevented EGEE-induced reproductive toxicity in rats.Item Tissues distribution of heavy metals and erythrocytes antioxidant status in rats exposed to Nigerian bonny light crude oil(Sage Publishers, 2011) Adedara, I. A.; Ebokaiwe, A. P.; Farombi, E. O.The harmful effects of folkloric uses of Nigerian bonny light crude oil (BLCO) in ailments management may outweigh the expected beneficial effects. We investigated the levels of heavy metal concentrations in the tissues as well as the effect of BLCO on the antioxidant status of erythrocytes of rats after oral exposure to 0, 200 and 800 mg/kg BLCO for 7 days. Analysis of heavy metal concentrations in BLCO showed that Zn > Fe > Pb > Cu > Ni. The trend of accumulation of the metals in the tissues is blood—Fe > Pb >Zn whereas Cu and Ni levels were not affected; Liver—Ni > Zn > Fe > Cu > Pb and Testes—Ni > Cu > Pb > Zn > Fe. The order of concentration of the metals in the tissues is as follows: iron—blood > liver > testes; zinc—liver > blood > testes; lead—blood > liver > testes; copper—testes > liver > blood; nickel—liver > testes > blood. Activities of the antioxidant enzymes of erythrocytes such as superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase increased significantly in a dose-dependent manner with significant elevation in hydrogen peroxide and malondialdehyde levels, whereas glutathione level was not significantly decreased in BLCO-treated animals. Collectively, the results showed that BLCO induces oxidative damage to erythrocytes of rats.Item Chemoprotective effects of kolaviron on ethylene glycol monoethyl ether-induced pituitary-thyroid axis toxicity in male rats(Blackwell Verlag GmbH, 2012) Adedara, I. A.; Farombi, E. O.Endocrine disrupting chemicals cause reproductive dysfunction by interacting with intricate regulation and cellular processes involve in spermatogenesis. This study investigated the probable mechanism of action of ethylene glycol monoethyl ether (EGEE) as an antiandrogenic compound as well as the effects of kolaviron upon co-administration with EGEE in rats. Adult male rats were exposed to EGEE (200 mg kg_1 bw) separately or in combination with either kolaviron [100 (KV1) and 200 (KV2) mg kg_1 bw] or vitamin E (50 mg kg_1bw) for 14 days. Western blot analysis revealed that the administration of EGEE adversely affected steroidogenesis in experimental rats by decreasing the expression of steroid acute regulatory (StAR) protein and androgen-binding protein (ABP). EGEE significantly decreased the activities of 3b-hydroxysteroid dehydrogenase (3b-HSD) and 17b-hydroxysteroid dehydrogenase (17b-HSD) but markedly increased sialic acid concentration in rat testes. EGEE-treated rats showed significant decreases in plasma levels of luteinising hormone (31%), testosterone (57.1%), prolactin (80.9%), triiodothyronine (65.3%) and thyroxine (41.4%), whereas follicle-stimulating hormone was significantly elevated by 76.9% compared to the control. However, co-administration of kolaviron or vitamin E significantly reversed the EGEE-induced steroidogenic dysfunction in rats. This study suggests that kolaviron may prove promising as a chemoprotective agent against endocrine pathology resulting from EGEE exposure.Item Chemoprotection of ethylene glycol monoethyl ether-induced reproductive toxicity in male rats by kolaviron, isolated biflavonoid from Garcinia kola seed(Sage Publishers, 2012) Adedara, I. A.; Farombi, E. O."The present study investigated the protective effect of kolaviron, a biflavonoid from the seed of Garcinia kola, on ethylene glycol monoethyl ether (EGEE)–induced reproductive toxicity in male rats. The protective effect of kolaviron was validated using vitamin E, a standard antioxidant. EGEE was administered at a dose of 200 mg/kg. Other groups of rats were simultaneously treated with kolaviron (100 and 200 mg/kg) and vitamin E (50 mg/kg) for 14 days. EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities but markedly increased the glutathione-Stransferase (GST) and lactate dehydrogenase (LDH) activities in the testes. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GPx, GST and LDH as well as in the level of GSH but significantly increased SOD activity with concomitant increase in hydrogen peroxide and malondialdehyde levels in both testes and spermatozoa. EGEE-exposed rats showed marked testicular degeneration with concomitant decrease in spermatozoa quantity and quality. Overall, EGEE causes reproductive dysfunction in rats by altering antioxidant systems in the testes and spermatozoa. Kolaviron or vitamin E exhibited protective effects against EGEE-induced male reproductive toxicity by enhancement of antioxidant status and improvement in spermatozoa quantity and quality.