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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 Abatement of the dysfunctional hypothalamic–pituitary–gonadal axis due to ciprofloxacin administration by selenium in male rats(Wiley Periodicals LLC, 2021) Adedara, I. A.; Awogbindin, I. O.; Mohammed, K. A.; Da-Silva, O. F.; Farombi, E. O.The present study examined the influence of selenium on ciprofloxacin‐mediated reproductive dysfunction in rats. The research design consisted of five groups of eight animals each. The rats were administered 135 mg/kg body weight of ciprofloxacin per se or simultaneously with selenium at 0.25 and 0.5 mg/kg for 15 uninterrupted days. Antioxidant and inflammatory indices were assayed using the testes, epididymis, and hypothalamus of the animals after sacrifice. Results revealed that ciprofloxacin treatment per se interfered with the reproductive axis as demonstrated by diminished serum hormonal levels, sperm quality, and enzymatic indices of testicular function, which were, however, abrogated following selenium co‐treatment. Besides this, administration of selenium attenuated the depletion of glutathione level, inhibition of catalase, superoxide dismutase, glutathione‐Stransferase and glutathione peroxidase activities with a concomitant reduction in reactive oxygen and nitrogen species, and lipid peroxidation in ciprofloxacintreated in rats. Selenium treatment also mitigated ciprofloxacin‐mediated elevation in nitric oxide level and of myeloperoxidase activity as well as histological lesions in the animals. Overall, selenium attenuated impairment in the male reproductive axis due to ciprofloxacin treatment through abatement of inflammation and oxidative stress in rats.Item Toxicological outcome of exposure to psychoactive drugs carbamazepine and diazepam on non-target insect Nauphoeta cinerea(Elsevier Ltd., 2021) Adedara, I. A.; Ajayi, B. O.; Afolabi, B. A.; Awogbindin, I. O.; Rocha, J. B. T.; Farombi, E. O.The continuous detection of human pharmaceuticals during environmental biomonitoring is a global concern because of thè menaces they may exert on non-target organisms. Carbamazepine (CBZ) and diazepam (DZP) are commonly prescribed psychotropic drugs which have been reported to coexist in thè environment globally. Nauphoeta cinerea is a common insect with high ecological impact. This study elucidated thè influence of co-exposure to DZP (0.5 and 1.0 pg kg-1 diet) and CBZ (1.5 and 3.0 pg kg~* diet) for 42 days on thè behavior and biochemical responses in Nauphoeta cinerea. Results showed that DZP alone did not induce adverse effect on thè behavior and antioxidant status in thè exposed insects. However, exposure to CBZ alone and binary mixtures of DZP and CBZ significantly decreased locomotor and exploratory accomplishments evidenced by decreased mobile episodes, total mobile time, maximum speed, total distance traveled, absolute turn angle, body rotation and path efficiency in comparison with control. The decline observed in thè exploratory activities of insects fed with CBZ alone and thè mixtures was confirmed by tracie plots and heat maps. Further, acetylcholinesterase and antioxidant enzyme activities decreased significantly whereas reactive oxygen and nitrogen species, nitric oxide and lipid peroxidation levels increased significantly in thè hemolymph, head and midgut of insects exposed to CBZ alone and thè mixtures. Collectively, CBZ alone and binary mixtures of CBZ and DZP .Item Hazardous impact of diclofenac exposure on thè behavior and antioxidant defense System in Nauphoeta cinerea(Elsevier Ltd., 2020) Adedara, I. A.; Awogbindin, I. O.; Afolabi, B. A.; Ajayi, B. O.; Rocha, J. B. T.; Farombi, E. O.Environmental pollution by pharmaceuticals such as diclofenac (DCF) is globally acknowledged to be a threat to thè ecosystems. Nauphoeta cinerea is an important insect with valuable ecological role. The present investigation aimed to elucidate thè impact of DCF on insects by assessing thè behavior and antioxidant defense response in nymphs ofN. cinerea exposed to DCF-contaminated food at 0,0.5,1.0 and 2.0 pg kg~* feed for 42 successive days. Subsequent to exposure period, neurobehavioral analysis using video-tracking software in a novel apparatus was performed before estimation of biochemical endpoints in thè head, midgut and hemolymph of thè insects. Results indicated that DCF-exposed insects exhibited marked reduction in thè maximum speed, total distance traveled, mobile episodes, total mobile time, body rotation, absolute turn angle and path efficiency, whereas thè total freezing time was increased compared with thè control. The diminution in thè exploratory activities of DCF-exposed insects was substantiated by heat maps and track plots. Additionally, DCF elicited marked diminution in antioxidant enzyme and acetylcholinesterase (AChE) activities along with increase in nitric oxide (NO), reactive oxygen and nitrogen species (RONS), and lipid peroxidation (LPO) levels in thè head, midgut and hemolymph of thè insects. Taken together, DCF elicited neurotoxicity and oxido-inflammatory stress in exposed insects. N. cinerea may be a suitable model insect for environmental risk assessment of pharmaceuticals in non-target insect species.Item Kolaviron via anti-inflammatory and redox regulatory mechanisms abates multi-walled carbon nanotubes-induced neurobehavioral deficits in rats(Springer-Verlag GmbH, 2020) Adedara, I. A.; Awogbindin, I. O.; Owoeye, O.; Maduako, I. C.; Ajeleti, A. O.; Owumi, S. E.; Patlola, A. K.; Farombi, E. O.Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochem- ical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone at 1 mg/kg body weight or orally co-administered with kolaviron at 50 and 100 mg/kg body weight for 15 consecutive days. Following exposure, neurobehavioral analysis using video-tracking software during trial in a novel environment indicated that co-administration of both doses of kolaviron significantly (p < 0.05) enhanced the locomotor, motor, and exploratory activities namely total distance traveled, maximum speed, total time mobile, mobile episode, path efficiency, body rotation, absolute turn angle, and negative geotaxis when compared with rats exposed to MWCNTs alone. Further, kolaviron markedly abated the decrease in the acetylcholinesterase activity and antioxidant defense system as well as the increase in oxidative stress and inflammatory biomarkers induced by MWCNT exposure in the cerebrum, cerebellum, and mid-brain of rats. The amelioration of MWCNT-induced neuronal degeneration in the brain structures by kolaviron was verified by histological and morphometrical analyses. Taken together, kolaviron abated MWCNT-induced neurotoxicity via anti-inflammatory and redox regulatory mechanisms.Item Nigral and ventral tegmental area lesioning induces testicular and sperm morphological abnormalities in a rotenone model of Parkinson’s disease(Elsevier B.V., 2020) Awogbindin, I. O.; Adedara, I. A.; Adeniyi, P. A.; Agedaha, A. E.; Oyetunde, B. F.; Olorunkalu, P. D.; Ogbuewua, E.; Akindoyeni, I. A.; Mustapha, Y. E.; Ezekiel, O. G.; Farombi, E. O.Although sexual health is affected by Parkinson’s disease (PD), the effect on testicular health and/or sperm quality is not well discussed. After 21 days of rotenone lesioning, we observed dopaminergic neuronal degeneration in the substantia nigra and hypothalamus. There were minimal SPACA-1-expressing epididymal spermatozoa with morphological abnormalities, scanty luminal spermatozoa and reduced testicular spermatids and post-meiotic germ cells indicating hypospermatogenesis. Occludin-expressing sertoli cells were dispersed over a wide area indicating compromised blood-testes barrier. Activated caspase-3 expression was intense while immunoreactivity of spermatogenic-enhancing SRY and GADD45 g was weak. Although serum follicle stimulating hormone level was not affected, the lesion was associated with reduced serum testosterone level, testicular oxidative damage and inhibition of acetylcholinesterase activity, even when rotenone was not detected in the testes. Together, dopaminergic lesions may mediate testicular and sperm abnormalities via the brain-hypothalamic- testicular circuit independent of the pituitary, thereby establishing a causal link between Parkinsonism and reproductive dysfunction.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 Diphenyl diselenide abrogates brain oxidative injury and neurobehavioural deficits associated with pesticide chlorpyrifos exposure in rats(Elsevier B.V., 2018) Adedara, I. A. || || || || || ||; Owoeye, O.; Awogbindin, I. O.; Ajayi, O. B.; Adeyemo, O. A.; Rocha, J. B. T.; Farombi, E. O.Exposure to pesticide chlorpyrifos (CPF) is associated with neurodevelopmental toxicity both in humans and animals. Diphenyl diselenide (DPDS) is a simple synthetic organoselenium well reported to possess antioxidant, anti-inflammatory and neuroprotective effects. However, there is paucity of information on the beneficial effects of DPDS on CPF-mediated brain injury and neurobehavioural deficits. The present study investigated the neuroprotective mechanism of DPDSin rats sub-chronically treated with CPF alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Endpoint analyses using video- tracking software in a novel environment revealed that co-treatment with DPDS significantly (p < 0.05) pro- tected against CPF-mediated locomotor and motor deficits precisely the decrease in maximum speed, total distance travelled, body rotation, absolute turn angle, forelimb grip strength as well as the increase in negative geotaxis and incidence of fecal pellets. The enhancement in the neurobehavioral activities of rats co-treated with DPDS was verified by track plot analyses. Besides, DPDS assuaged CPF-induced decrease in acetylcholinesterase and antioxidant enzymes activities and the increase in myeloperoxidase activity and lipid peroxidation level in the mid-brain, cerebral cortex and cerebellum of the rats. Histologically, DPDS co-treatment abrogated CPF- mediated neuronal degeneration in the cerebral cortex, dentate gyrus and cornu ammonis3 in the treated rats. In conclusion, the neuroprotective mechanisms of DPDS is related to the prevention of oxidative stress, enhance- ment of redox status and acetylcholinesterase activity in brain regions of the rats. DPDS may be a promising chemotherapeutic agent against brain injury resulting from CPF exposure.Item Suppression of the brain-pituitary-testicular axis function following acute arsenic and manganese co-exposure and withdrawal in rats(Elsevier GmbH., 2017) Adedara, I. A.; Abolaji, A. O.; Awogbindin, I. O.; Farombi, E. O.Despite the fact that most environmental exposures to metals do not occur in isolation, the combined effects of metal mixtures on brain–pituitary–gonadal axis are poorly known. The present study investigated the impacts of co-exposure to arsenic (As) and manganese (Mn) on sperm characteristics, reproductive hormones and selected oxidative stress indices in the brain, testes and epididymis of rats following exposure for 15 consecutive days to 60 mg/L of AsO₃Na and 30 mg/L of MnCl₂ in drinking water. The results showed that while brain weight remained unaffected, the fluid intake and the weights of testes and epididymis significantly (p < 0.05) decreased in all the treatment groups. A significant decrease in the body weight gain when compared with control was noted only in the co-exposed rats. Moreover, the significant decreases in the antioxidant status in brain, testes and epididymis as well as in the circulatory concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone were similar following separate or combined exposure of rats to As and Mn. The marked oxidative damage in the investigated tissues was accompanied by a significant decrease in the sperm quantity and quality in all the treated rats when compared with the control. Interestingly, most of the parameters determined immediately after the exposure period persisted in rats from the withdrawal experiment. Collectively, co-exposure to As and Mn suppressed the brain–pituitary–testicular axis function and the post-testicular events such as sperm function possibly via a mechanism involving persistent oxidative stress and endocrine disruption in the exposed rats.Item Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice(Elsevier Inc., 2017) Adedara, I. A.; Ajayi, B. O.; Awogbindin, I. O.; Farombi, E. O.Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice.
