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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 Pharmacological activity of 6-Gingerol in Dextran Sulphate Sodium-induced ulcerative colitis in BALB/c Mice(John Wiley & Sons, Ltd., 2015) Ajayi, B. O.; Adedara, I. A.; Farombi, E. O.Gingerols are phenolic compounds in ginger (Zingiber officinale), which have been reported to exhibit antiinflammatory, antioxidant, and anticancer properties. The present study aimed at evaluating the possible pharmacologic activity of 6-gingerol in a mouse model of dextran sulphate sodium (DSS)-induced ulcerative colitis. Adult male mice were exposed to DSS in drinking water alone or co-treated with 6-gingerol orally at 50, 100, and 200 mg/kg for 7 days. Disease activity index, inflammatory mediators, oxidative stress indices, and histopathological examination of the colons were evaluated to monitor treatment-related effects of 6-gingerol in DSS-treated mice. Administration of 6-gingerol significantly reversed the DSS-mediated reduction in body weight, diarrhea, rectal bleeding, and colon shrinkage to near normal. Moreover, 6-gingerol significantly suppressed the circulating concentrations of interleukin-1β and tumor necrosis factor alpha and restored the colonic nitric oxide concentration and myeloperoxidase activity to normal in DSS-treated mice. 6-Gingerol efficiently prevented colonic oxidative damage by increasing the activities of antioxidant enzymes and glutathione content, decreasing the hydrogen peroxide and malondialdehyde levels, and ameliorated the colonic atrophy in DSS-treated mice. 6-Gingerol suppressed the induction of ulcerative colitis in mice via antioxidant and antiinflammatory activities, and may thus represent a potential anticolitis drug candidate.Item Kolaviron protects against ethylene glycol monoethyl ether-induced toxicity in boar spermatozoa(Blackwell Verlag GmbH, 2014) Adedara, I. A.; Farombi, E. O.This study investigated the ameliorative effects of kolaviron (a biflavonoid from the seed of Garcinia kola) and vitamin C on ethylene glycol monoethyl ether (EGEE)-induced oxidative damage in boar spermatozoa in vitro. EGEE (1.0 mM) was incubated with boar spermatozoa for 3 h with or without either kolaviron (50 and 100 lM) or vitamin C (1.0 mM). Spermatozoa parameters were determined hourly during the incubation period, whereas aminotransferases and alkaline phosphatase activities and oxidative stress indices were assessed after the incubation period. Results showed a time-dependent decline in spermatozoa motility and viability with significant elevation in total abnormalities in EGEE-treated spermatozoa. Exposure to EGEE resulted in significant increase in aminotransferases, alkaline phosphatase and superoxide dismutase (SOD) activities, whereas it markedly decreased glutathione (GSH) level, catalase (CAT) and glutathione S-transferase (GST) activities with concomitant increase in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels. Pre-treatment of spermatozoa with kolaviron or vitamin C significantly decreased H2O2 and MDA levels, improved spermatozoa characteristics and ameliorated oxidative damage in EGEE-treated spermatozoa. Taken together, EGEE exhibited its spermatotoxicity via induction of oxidative stress. The protective effects by kolaviron and vitamin C against EGEE-induced oxidative damage may be due to their intrinsic antioxidative potentials.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 Influence of kolaviron and vitamin E on ethylene glycol monoethyl ether-induced haematotoxicity and renal apoptosis in rats(John Wiley & Sons, Ltd., 2013) Adedara, I. A.; Farombi, E. O.The present study investigated the protective effects of kolaviron, a biflavonoid from the seed of Garcinia kola, and vitamin E on ethylene glycol monoethyl ether (EGEE)-induced haematotoxicity and renal apoptosis in male rats. EGEE was administered at a dose of 200 mg kg_1 alone or simultaneously administered with kolaviron (100 and 200 mg kg_1) and vitamin E (50 mg kg_1) for 14 days. Results of haematological examination showed that white blood cells, platelets, neutrophils and mean corpuscular haemoglobin concentration were significantly lower, whereas lymphocytes were increased in EGEE-exposed rats compared with those in the control. Administration of EGEE caused a significant decrease in the superoxide dismutase and catalase activities as well as in the glutathione level but significantly increased glutathione S-transferase activity and levels of hydrogen peroxide and lipid peroxidation in kidneys of rats compared with those in the control. Also, EGEE-treated rats showed significant elevation in the serum urea and creatinine with marked increase in the frequency of terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay-positive apoptotic cells in the tubular epithelial cells in comparison with the control. Co-administration with kolaviron or vitamin E exhibited chemoprotective effects against EGEE-mediated haematotoxicity, augmented renal antioxidant status and prevented the induction of renal apoptosis.Item Lack of recovery from hepatic oxidative damage in rats treated with Nigerian bonny light crude oil(John Wiley & Sons, Ltd., 2012) Adedara, I. A.; Farombi, E. O.The use of Nigerian bonny light crude oil (BLCO) in the treatment of gastrointestinal disorders, burns, foot ulcers and reproductive capacity is a common practice in the southern part of Nigeria. Towards understanding the mechanism and the reversibility of hepatotoxicity induced by BLCO, adult male Wistar rats were orally administered with BLCO at 0, 50, 100 and 200 mg kg 1 for 21 days. One-half of the rats were sacrificed on day 22, whereas the remaining half stayed for an additional 21 days without treatment. Whereas the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione S-transferase were significantly (p<0.05) increased, gamma glutamyl transferase activity was significantly decreased in a dose-dependent manner. The levels of glutathione, hydrogen peroxide and malondialdehyde were significantly elevated in BLCO-treated animals. In addition, hepatic degeneration was accompanied with elevation in serum aminotransferases activities without affecting bilirubin levels. Whereas most of the above-mentioned parameters were consistent in animals from withdrawal experiment, both total and conjugated bilirubin levels were significantly increased after 21 days of BLCO-treatment withdrawal. Taken together, BLCO-induced hepatotoxicity could be due to increased oxidative stress which was not reversible upon withdrawal of treatment within the time course of investigation in male rats.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.Item Induction of oxidative stress in liver and kidney of rats exposed to Nigerian bonny light crude oil(Wiley Periodicals, Inc., 2010) Adedara, I. A.; Teberen, R.; Ebokaiwe, A. P; Ehwerhemuepha, T.; Farombi, E. O.The local population of Niger-Delta in the Southern part of Nigeria have used bonny light crude oil (BLCO) as a remedy for various ailments and are exposed to some extent to this widespread environmental contaminant or its metabolites through the food chain. BLCO’s hepatorenal toxicity was studied using oxidative stress indices to elucidate the precise nature and mechanism of action. BLCO was orally administered at concentrations of 0, 200, 400, and 800 mg kg21 to adult male rats for 7 days. After exposure, kidney weight was unaffected, but liver weight decreased significantly at 800 mg kg21 only compared with control. BLCO exposure resulted in dose-dependent elevation of serum aminotransferases, total bilirubin, urea, and creatinine. Activities of superoxide dismutase and catalase decreased significantly, whereas c-glutamyltransferase activity and the level of glutathione increased significantly in BLCO-treated animals compared with control in both liver and kidney of rat. Renal activities of glucose-6- phosphatase and 50-nucleotidase markedly decreased in a dose-dependent manner in BLCO-exposed rats. In addition, the levels of hydrogen peroxide and lipid peroxidation significantly increased, dose dependently, in liver and kidney of BLCO-treated rats compared with control. BLCO-treated rats showed marked degeneration of kidney evident in cortical hemorrhages, tubular necrosis, protein casts, and cellular infiltration. However, no treatment-related liver histopathology was observed. The results suggested that BLCO elicits disruption of antioxidant status and concomitant elevation of hydrogen peroxide and lipid peroxidation differentially in liver and kidney of rats. The hepatorenal toxicity of BLCO could be due to induction of oxidative stress in liver and kidney.