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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 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 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.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 Low doses of multi-walled carbon nanotubes elicit hepatotoxicity in rats with markers of oxidative stress and induction of proinflammatory cytokines(Elsevier Inc., 2018) Adedara, I. A.; Anao, O. O.; Forcados, G. E.; Awogbindin, I. O.; Agbowo, A.; Ola-Davies, O. E.; Patlola, A. K.; Tchounwou, P. B.; Farombi, E. O.The investigation into the potential health risks associated with the use of engineered nanoparticles is a major scientific interest in recent years. The present study elucidated the involvement of proinflammatory cytokines, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in carboxylated multi-walled carbon nanotubes (MWCNTs)-induced hepatotoxicity. Pubertal rats were exposed to purified MWCNTs at 0, 0.25, 0.50, 0.75 and 1.0 mg/kg for 5 consecutive days. Results indicated that exposure to MWCNTs caused liver damage evidenced by significant elevation in serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) when compared with control. Moreover, MWCNTs significantly decreased superoxide dismutase (SOD) and glutathione S-transferase (GST) activities as well as glutathione level whereas it significantly increased catalase (CAT) and glutathione peroxidase (GPx) activities in liver of the treated rats. Moreover, the dose-dependent increase in hepatic hydrogen peroxide (H2O2) and lipid peroxidation levels were accompanied by marked increase in micronucleated polychromatic erythrocytes (MNPCE) in the MWCNTs-treated rats. Administration of MWCNTs significantly increased serum concentrations of pro-inflammatory cytokines namely interleukin-1b (IL-1b), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) in the treated rats. Immunohistochemical analysis showed significantly increased COX-2 and iNOS protein expressions in the liver of MWCNTs-treated rats. In conclusion, carboxylated MWCNTs induces hepatic damage via disruption of antioxidant defense systems, promotion of pro-inflammatory cytokines generation and expression of COX-2 and i-NOS in rats.Item Dietary co-exposure to methylmercury and monosodium glutamate disrupts cellular and behavioral responses in the lobster cockroach, Nauphoeta cinerea model(Elsevier B.V., 2018) Afolabi, B. A. || || ||; Adedara, I. A.; Souza, D. O.; Rocha, J. B. T.The present study aims to investigate the effect of monosodium glutamate (MSG) both separately and combined with a low dose of methylmercury (MeHg) on behavioral and biochemical parameters in Nauphoeta cinerea (lobster cockroach). Cockroaches were fed with the basal diet alone, basal diet + 2% NaCl, basal diet + 2% MSG; basal diet+0.125 mg/g MeHg, basal diet+0.125 mg/g MeHg + 2% NaCl; and basal diet+0.125 mg/g MeHg + 2% MSG for 21 days. Behavioral parameters such as distance traveled, immobility and turn angle were automatically measured using ANY-maze video tracking software (Stoelting, CO, USA). Biochemical end-points such as acetylcholinesterase (AChE), glutathione-S-transferase (GST), total thiol and TBARS were also evaluated. Results show that MeHg+NaCl, increased distance traveled while MeHg+MSG increased time immobile. AChE activity was significantly reduced in cockroaches across all the groups when compared to the control. There was no significant alteration in GST activity and total thiol levels. It could be that both NaCl and MSG potentiates the neurotoxic effect of MeHg in cockroaches.