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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 Protocatechuic acid ameliorates neurobehavioral defìcits via suppression of H) oxidative damage, inflammation, caspase-3 and acetylcholinesterase activities in diabetic rats(Elsevier Ltd., 2019) Adedara, I. A. || || || ||; Fasina, O. B.; Ayeni, M. F.; Ajayi, O. M.; Farombi, E. O.Clinical and experimental data have demonstrated that diabetes is associated with neurological complications. Protocatechuic acid (PCA) is a phenolic phytochemical widely reported to possess antidiabetic property. However, there is no scientific information on the influence of PCA on diabetes-induced neurotoxicity. The present study aimed at investigating the neuroprotective mechanism of PCA in streptozotozin (STZ)-induced type 1 diabetic rats orally treated with PCA (50 mg/kg body weight) or glibenclamide (5 mg/kg body weight) for 45 consecutive days. Locomotor behavior was analyzed using video-tracking software during the 8-min trial in a novel environment whereas the pancreas, cerebrum and cerebellum of the rats were processed for biochemical analyses. Results showed that treatment of diabetic rats with PCA at 50 mg/kg significantly (p < 0.05) im- proved the locomotor and motor activities including the average speed, total time mobile, distance travelled, body rotation, turn angle, forelimb grip and grooming when compared with untreated diabetic rats. Moreover, the prevention of diabetes-mediated increase in acetylcholinesterase activity, biomarkers of inflammatory and oxidative stress as well as caspase 3 activity by PCA treatment was accompanied by improved pancreatic, cer- ebral and cerebellar architectures. Collectively, the neuroprotective mechanisms of PCA is related to its anti- oxidant, anti-inflammatory and anti-apoptotic activities.Item 6-Gingerol abates benzo[a]pyrene-induced colonic injury via suppression of oxido-inflammatory stress responses in BALB/c mice(Elsevier B.V., 2019) Ajayi, B. O. || ||; Adedara, I. A.; Farombi, E. O.Exposure to benzo[a]pyrene (BaP), the most toxic polycyclic aromatic hydrocarbon and a procarcinogen, is a global health concern which necessitates preventive measures. [6]-Gingerol (6-G), the most pharmacologically active constituent of ginger has been reported to promote gut health in various experimental settings. This study investigated the role of 6-G in BaP-induced colonic oxidative and inflammatory stress responses in mice. Experimental mice were randomly assigned into five groups of eight mice each and were orally gavage with BaP (125 mg/kg) singly or in combination with 6-G at 50 and 100 mg/kg for 14 consecutive days. Following sacrifice, the colonic activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), myeloperoxidase (MPO) as well as levels of glutathione (GSH), nitrites and lipid peroxidation (LPO) were assessed spectrophotometrically. Moreover, colonic concentration of epoxide hydrolase (EPXH), tumor necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were assessed using ELISA. Administration of 6-G augmented BaP detoxification and colonic antioxidant status by increasing the EPXH, GST, SOD and CAT activities, GSH level with concomitant decrease in MDA level when compared with BaP alone group. In addition, 6-G suppressed BaP-induced colonic inflammation by decreasing MPO activity as well as nitrites, TNF-α, IL-1β, COX-2 and iNOS levels when compared with BaP alone group. In conclusion, 6-G protected against a decrease in colonic epoxide detoxifying enzymes and antioxidant defense mechanisms caused by BaP.Item Dietary protocatechuic acid abrogates male reproductive dysfunction in streptozotocin-induced diabetic rats via suppression of oxidative damage, inflammation and caspase-3 activity(Elsevier B.V., 2019) Adedara, I. A. || || || || ||; Okpara, E. S.; Busari, E. O.; Omole, O.; Owumi, S. E.; Farombi, E. O.Clinical and experimental studies demonstrated that reproductive dysfunction is a non-lethal complication of diabetes. Protocatechuic acid (PCA) reportedly elicited several pharmacological effects in diabetic animals. However, there is paucity of information on the role of PCA in reproductive dysfunction associated with diabetes. The present study investigated the influence of PCA on the functional changes along the hypothalamicpituitary-testicular axis in male diabetic rats. Streptozotocin (STZ)-induced diabetic rats were orally treated with PCA at 25 and 50 mg/kg body weight for 45 consecutive days. Results showed that PCA treatment significantly dwindled blood glucose level as well as prevented diabetes mediated decrease in body weight gain and organosomatic indices of the testes and epididymis in the treated rats. Moreover, PCA increased the reproductive hormone levels, marker enzymes of testicular function and sperm functional characteristics in the treated rats. Further, PCA augmented the antioxidant status, inhibited lipid peroxidation and suppressed pro-inflammatory biomarkers including myeloperoxidase (MPO) activity, nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels as well as caspase-3 activity inhypothalamus, testes and epididymis of diabetic rats. Collectively, PCA effectively abrogated reproductive deficits in diabetic rats via mechanisms involving suppression of oxidative stress, inflammation and caspase-3 activity along with enhancement of sperm functional parameters. Thus, PCA may preserve reproductive health in humans suffering from diabetes.Item Impact of binary waterborne mixtures of nickel and zinc on hypothalamic-pituitary-testicular axis in rats(Elsevier Ltd., 2019) Adedara, I. A.; Abiola, M. A.; Adegbosin, A. N.; Odunewu, A. A.; Farombi, E. O.Several evidences from the literature showed that the coexistence of nickel and zinc in polluted waters is related to the similarity in their geogenic and anthropogenic factors. Although most environmental exposures to metals do not occur singly, there is a paucity of scientific knowledge on the effects of zinc and nickel co-exposure on mammalian reproductive health. The present study investigated the influence of co-exposure to nickel and zinc on male reproductive function in rats. Experimental rats were co- exposed to environmentally relevant concentrations of waterborne nickel (75 and 150 mg NiCl2 L-1) and zinc (100 and 200 mg ZnCl2 L-1) for 45 successive days. Subsequently, reproductive hormones were assayed whereas the hypothalamus, epididymis and testes of the rats were processed for the assessment of oxidative stress and inflammation indices, caspase-3 activity and histology. Results indicated that co- exposure to nickel and zinc significantly (p < 0.05) abolished nickel-mediated diminution of antioxidant defense mechanisms while diminishing levels of reactive oxygen and nitrogen species and lipid per- oxidation in the hypothalamus, epididymis and testes of the exposed rats. Additionally, co-exposure to zinc abated nickel-mediated diminutions in luteinizing hormone, follicle-stimulating hormone, serum and intra-testicular testosterone with concomitant enhancement of sperm production and quality. Further, zinc abrogated nickel-mediated elevation in inflammatory biomarkers including nitric oxide, tumor necrosis factor alpha, interleukin-1 beta as well as caspase-3 activity. The protective influence of zinc on nicked-induced reproductive toxicity was well supported by histological data. Overall, zinc ameliorated nickel-induced reproductive dysfunctionItem 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 6-Gingerol improves testicular function in mice model of chronic ulcerative colitis(Sage Publishers, 2018) Farombi, E. O.; Adedara, I. A.; Ajayi, B. O.; Idowu, T. E.; Eriomala, O. O.; Akinbote, F. O.The persistent inflammation and oxidative stress at the local site in ulcerative colitis reportedly extend to the testes via systemic circulation resulting in testicular dysfunction. The influence of 6-gingerol (6G), a phenolic compound isolated from Zingiber officinale, on colitis-mediated testicular dysfunction in mice was investigated in this study. Chronic ulcerative colitis was induced in mice using 2.5% dextran sulfate sodium (DSS) in drinking water for three cycles. Each cycle consisted of 7 consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. 6G (100 mg/kg) or sulfasalazine (SZ; 100 mg/kg) was orally administered alone or in combination with DSS-treated water during the three cycles. SZ served as standard reference drug for colitis in this study. 6G significantly prevented the incidence of rectal bleeding, decrease in the body weight gain and colon mass index in DSS-exposed mice. 6G significantly prevented colitis-mediated decreases in luteinizing hormone, follicle-stimulating hormone and testosterone and decreases oxidative stress indices, pro-inflammatory cytokines and caspase-3 activity with concomitant augmentation of antioxidant enzymes activities, sperm characteristics, marker enzymes of testicular function and histoarchitecture in DSS-exposed mice. 6G exerted protective influence against ulcerative colitis-induced testicular damage via mechanisms involving its antioxidant and anti-inflammatory properties.Item Pretreatment with taurine prevented brain injury and exploratory behaviour associated with administration of anticancer drug cisplatin in rats(Elsevier Masson SAS., 2018) Owoeye, O.; Adedara, I. A.; Farombi, E. O.The neurotoxicity associated with cisplatin treatment is one of the major side effects compromising the efficacy of the anti-cancer treatment. The present study investigated the possible protective effects of taurine, an in- tracellular amino acid, on cisplatin-induced brain injury and exploratory behaviour using five groups of ten female rats each. Group I received drinking water only. Group II orally received taurine alone at 200 mg/kg whereas Group III received cisplatin alone intraperitoneally at 10mg/kg. Groups IV and V were treated with taurine at 100 and 200mg/kg respectively for sixteen consecutive days and a single intraperitoneal injection of cisplatin on day 13 to induce neurotoxicity. Endpoint analyses using video-tracking software revealed that cisplatin administration alone caused neurobehavioral deficits evinced by marked decrease in the total distance travelled, average speed, total time mobile, total mobile episode, number of crossing and absolute turn angle. Furthermore, cisplatin alone significantly suppressed brain antioxidant defense mechanisms, elevated nitric oxide and lipid peroxidation levels whereas it increased acetylcholinesterase activity in the treated rats. However, rats pretreated with taurine exhibited significant improvement in behavioural performance and brain antioxidant status with concomitant decrease in acetylcholinesterase activity and oxidative stress indices when compared with cisplatin alone group. Histologically, taurine pretreatment prevented cisplatin-induced neuronal death in the cerebral and cerebellar cortices, caudo-putamen and hippocampus as well as abrogated cisplatin- mediated decrease in the dendritic arborization and mean diameter of the somata of pyramidal neurons in the treated rats. In conclusion, taurine may be a possible protective supplement to reduce cisplatin-induced side- effects including neurotoxicity in patients undergoing cisplatin treatment.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.