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Item Indole-3-propionic acid mitigates chlorpyrifos-mediated neurotoxicity by modulating cholinergic and redox-regulatory systems, inflammatory stress, apoptotic responses and DNA damage in rats(Elsevier B.V., 2022) Owumi, S. E.; Adedara, I. A.; Oyelere, A. K.This study probed the neuroprotective influence of indole-3-propionic acid (IPA) in rats exposed to chlorpyrifos (CPF) alone at 5 mg/kg body weight or co-administered with IPA at 12.5 and 25 mg/kg for 14 days. Behavioral data indicated that IPA significantly (p < 0.05) abated CPF-mediated anxiogenic-like behaviors with concomitant improvement in the locomotor and exploratory behaviors as substantiated by track plots and heat maps data. Also, IPA mitigated CPF-mediated diminution in cholinergic and antioxidant defense systems whereas it mark- edly improved thioredoxin level and thioredoxin reductase activity in cerebral and cerebellar tissues of the animals. Co-administration of IPA significantly enhanced anti-inflammatory cytokine, interleukin-10 but sup- pressed oxidative and inflammatory stress, caspase-9 and caspase-3 activation with concomitant reduction in 8- hydroxy-2'-deoxyguanosine (8-OHdG) level and histological damage. Collectively, IPA-mediated neuro- protection involves modulation of cholinergic and redox-regulatory systems, inflammatory stress, apoptotic re- sponses and DNA damage in cerebrum and cerebellum of rats.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 Neuroprotective role of gallic acid in aflatoxin Bi-induced behavioral abnormalities in rats(Wiley Periodicals LLC, 2020) Adedara, I. A.; Owumi, S. E.; Oyelere, A. K.; Farombi, E. O.The neurotoxic impact of dietary exposure to aflatoxin Bi (AFBJ is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phyto- chemical with potent anticancer, anti-inflammatory, and antioxidant activities. There is a knowledge gap on thè influence of GA on AFBi-induced neurotoxicity. This study probed thè influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFBi per se (75pg/kg body weight) or administered together with GA (20 and 40mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video-tracking software demonstrated sig-nificant (p<.05) abatement of AFBrinduced anxiogenic-like behaviors (increased freezing, urination, and fecal bolus discharge), motor and locomotor inadequacies, namely increased negative geotaxis and diminished grip strength, absolute turn angle, total time mobile, body rotation, maximum speed, and total distance traveled by GA. The improvement of exploratory behavior in animals that received both AFBi and GA was confirmed by track plots and heat maps appraisal. Abatement of AFBj-induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in thè cerebellum and cerebrum of rats. Additionally, GA treatment abro- gated AFBi-mediated decrease in interleukin-10 and elevation of inflammatory in- dices, namely tumor necrosis factor-a, myeloperoxidase activity, interleukin-l|3, and nitric oxide. Further, GA treatment curtailed caspase-3 activation and histological injuries in thè cerebral and cerebellar tissues. In conclusion, abatement of AFBi-induced neurobehavioral abnormalities by GA involves anti-inflammatory, antioxidant, and antiapoptotic mechanisms in rats.Item Neurobehavioural and biochemical responses associated with exposure to binary waterborne mixtures of zinc and nickel in rats(1382-6689, 2020) Adedara, I. A.; Adegbosin, A. N.; Owoeye, O.; Abiola, M. A.; Odunewu, A. A.; Owoeye, O.; Owumi, S. E.; Farombi, E. O.Environmental and occupational exposure to metal mixtures due to various geogenic and anthropogenic ac- tivities poses a health threat to exposed organisms. The outcome of systemic interactions of metals is a topical area of research because it may cause either synergistic or antagonistic effect. The present study investigated the impact of co-exposure to environmentally relevant concentrations of waterborne nickel (75 and 150 pg NiCl 2L-1) and zinc (100 and 200pg ZnC^L-1) mixtures on neurobehavioural performance of rats. Locomotor, motor and exploratory activities were evaluated using video-tracking software during trial in a novel arena and thereafter, biochemical and histological analyses were performed using the cerebrum, cerebellum and liver. Results indicated that zinc significantly (p < 0.05) abated the nickel-induced locomotor and motor deficits as well as improved the exploratory activity of exposed rats as verified by track plots and heat map analyses. Moreover, zinc mitigated nickel-mediated decrease in acetylcholinesterase activity, elevation in biomarkers of liver damage, levels of reactive oxygen and nitrogen species as well as lipid peroxidation in the exposed rats when compared with control. Additionally, nickel mediated decrease in antioxidant enzyme activities as well as the increase in tumour necrosis factor alpha, interleukin-1 beta and caspase-3 activity were markedly abrogated in the cerebrum, cerebellum and liver of rats co-exposed to nickel and zinc. Histological and histomorphome- trical analyses evinced that zinc abated nickel-mediated neurohepatic degeneration as well as quantitative re- duction in the widest diameter of the Purkinje cells and the densities of viable granule cell layer of dentate gyrus, pyramidal neurones of cornu ammonis 3 and cortical neurons in the exposed rats. Taken together, zinc abrogated nickel-induced neurohepatic damage via suppression of oxido-inflammatory stress and caspase-3 activation in rats.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 Gallic acid enhances reproductive function by modulating oxidoinflammatory and apoptosis mediators in rats exposed to aflatoxin-B1(Society for Experimental Biology and Medicine, 2020) Owumi, S. E.; Adedara, I. A.; Akomolafe, A. P.; Farombi, E. O.; Oyelere, A. K.Aflatoxin B1 (AFB1) is reported to elicit adverse reproductive outcomes in animals. Gallic acid (GA) is known to exhibit antioxidant and inflammatory bioactivities. The impact of GA on AFB1-facilitated reproductive dysfunction is nonexistent in literature. This investigation elucidated GA protective effect on AFB1-induced reproductive toxicities in rats, exposed for 28 consecutive days to AFB1 (75 mg/kg), or co-treated with GA (20 or 40 mg/kg) body weight. AFB1 significantly (p<0.05) reduced testicular function biomarkers, serum hormonal levels, and functional sperm characteristics in experimental animals. GA abated AFB1-induced increases (p<0.05) in lipid peroxidation and reactive oxygen and nitrogen species, suppressed myeloperoxidase, interleukin-1b, nitric oxide, and tumor necrosis factor-a levels—inflammatory biomarkers—in testes, epididymis, and hypothalamus. Furthermore, GA improved antioxidant defenses and alleviated reduction in interleukin-10, caspase-3 activation, and histological variations in epididymis, testes, and hypothalamus of rats dosed with AFB1. Conclusively, GA enhanced reproductive function in AFB1-exposed rats by modulating inflammatory, oxidative stress, and apoptosis mediators.Item Protocatechuic acid modulates reproductive dysfunction linked to furan exposure in rats(Elsevier B.V., 2020) Owumi, S. E.; Adedara, I. A.; Farombi, E. O.; Oyelere, A. K.The reproductive toxicity associated with furan exposure in both animals and humans has been documented. Protocatechuic acid (PCA), a dietary polyphenolic chemical, reportedly elicits beneficial effects on the male reproductive system. However, the influence of PCA on the reproductive toxicity related to furan exposure is unavailable in the literature. The current study evaluated the effects of PCA on the dysfunctional reproductive axis caused by furan exposure in rats. Experimental animals were exposed to furan (8 mg/kg) or co-treated with furan (8 mg/kg) and PCA (25 or 50 mg/kg) for twenty-eight successive days. Results revealed that PCA treatment significantly alleviated furan-mediated declines in sperm production and characteristic qualities as well as in serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, and testosterone. Further, PCA attenuated furan-induced reduction in antioxidant enzyme activities and testicular function marker enzymes, namely lactate dehydrogenase, glucose-6-phosphate dehydrogenase, acid phosphatase, and alkaline phospha- tase. PCA effectively mitigated furan-mediated increases in myeloperoxidase activity, levels of reactive oxygen and nitrogen species, nitric oxide, tumour necrosis factor-alpha, and interleukin-1^ in testes, epididymis, and hypothalamus of rats. Moreover, PCA increased anti-inflammatory cytokine interleukin-10 but suppressed cas- pase-9 and caspase-3 activities and ameliorated injuries in the testes, epididymis, and hypothalamus of furan- treated rats. In conclusion, PCA ameliorated deficits in the hypothalamic-pituitary-gonadal axis function in furan-exposed rats by suppressing oxido-inflammatory stress and apoptosis.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 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 Dietary protocatechuic acid ameliorates dextran sulphate sodium-induced ulcerative colitis and hepatotoxicity in rats(The Royal Society of Chemistiy, 2016) Farombi, E. O. || || || || || || ||; Adedara, I. A.; Awoyemi, O. V.; Njoku, C. R.; Micah, G. O.; Esogwa, C. U.; Owumi, S. E.; Olopade, J. O.The present study investigated the antioxidant and anti-inflammatory effects of dietary protocatechuic acid (PCA), a simple hydrophilic phenolic compound commonly found in many edible vegetables, on dextran sulphate sodium (DSS)-induced ulcerative colitis and its associated hepatotoxicity in rats. PCA was administered orally at 10 mg kg-1 to dextran sulphate sodium exposed rats for five days. The result revealed that administration of PCA significantly (p < 0.05) prevented the incidence of diarrhea and bleed- ing, the decrease in the body weight gain, shortening of colon length and the increase in colon mass index in DSS-treated rats. Furthermore, PCA prevented the increase in the plasma levels of pro-inflamma- tory cytokines, markers of liver toxicity and markedly suppressed the DSS-mediated elevation in colonie nitric oxide concentration and myeloperoxidase activity in the treated rats. Administration of PCA significantly protected against colonie and hepatic oxidative damage by increasing the antioxidant status and concomitantly decreased hydrogen peroxide and lipid peroxidation levels in the DSS-treated rats. More- over, histological examinations confirmed PCA chemoprotection against colon and liver damage. Immunohistochemical analysis showed that PCA significantly inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in the colon of DSS-treated rats. In conclusion, the effective chemoprotective role of PCA in colitis and the associated hepatotoxicity is related to its intrinsic anti-inflammatory and anti-oxidative properties.
