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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 Taurine reverses sodium fluoride-mediated increase in inflammation, caspase-3 activity, and oxidative damage along the brain-pituitary-gonadal axis in male rats(Canadian Science Publishing, 2017) Adedara, I. A.; Olabiyi, B. F.; Ojuade, T. D.; Idris, U. F.; Onibiyo, E. M.; Farombi, E. O.Excessive exposure to fluoride is associated with male reproductive dysfunction in humans and animals. Taurine (2-aminoethane sulfonic acid) is a free intracellular β-amino acid with antioxidant, anti-inflammatory, and neuroprotective properties. However, the effect of taurine on fluoride-induced reproductive toxicity has not been reported. The present study investigated the influence of taurine on sodium fluoride (NaF)-induced functional changes along the brain–pituitary–gonadal axis in male rats. NaF was administered singly in drinking water at 15 mg•L⁻¹ alone or orally co-administered by gavage with taurine at 100 and 200 mg•kg⁻¹ body mass•day⁻¹ for 45 consecutive days. Results showed that taurine significantly prevented NaF-induced increases in oxidative stress and inflammation levels in the brain, testes, and epididymis of the treated rats. Moreover, taurine reversed NaF-induced elevation in inflammatory biomarkers and caspase-3 activity as well as histological damage in the brain, testes, and epididymis of the treated rats. The significant reversal of NaF-induced decreases in testosterone level and testicular activities of acid phosphatase, alkaline phosphatase, and lactate dehydrogenase by taurine was accompanied by enhancement of sperm functional characteristics in the treated rats. Taurine may be a possible chemopreventive candidate against reproductive dysfunction resulting from fluoride exposure.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 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.Item Evaluation of antioxidant properties of Mallotus oppositifolium in in-vitro, in-vivo and ex-vivo model systems(College of Medicine, University of Ibadan, 2010) Adedara, I. A.; Adesanoye, O. A.; Farombi, E. O.The protective effect of antioxidants and naturai !y occurring substances against oxidative stress damage has recently attracted much attention. The ieaves of Mallotus oppositifolium, a shrub of thè famìly Euphorbiacea that grows in many parts of Africa, are used in folk medicine and herbal preparations for die treatment of dysentery, worms and malaria. The study in vestigated thè antioxidant properties of thè methanolic extract of thè Ieaves of Mallotus oppositifolium (MEMO) in comparison with butylated hydroxyl anisole (BHA) as a standard antioxidant using three free radicai generators viz hydrophilic radicai generator 2,2-azobis(2- amidino propane) dihydrochloride (AAPH), hydrophobic radicai generator 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN) and hydroxyl radicai and non-specific radicai generator Fe2+/ascorbate System in an in vitro, in vivo and ex-vivo model systems. Phytochemical analysis of thè Ieaves extract was al so assessed. Phytochemical analysis of thè powdered Ieaves revealed thè presence of alkaloids, tannins, cardenolides and saponins. In vitro study indicated that while MEMO failed to inhibit lipid peroxidation (LPO) induced by AAPH, while BHA offered 55.5% inhibition. In addition, while AMVN- induced LPO was inhibited by 17.7% and 29.4% by MEMO and BHArespectively, Fe2+/ascorbate system- induced LPO was inhibited by 57.9% and 78.9% by MEMO and BHArespectively. Ex-vivo studies showed that MEMO at lOOmg/kg bw reduced malondialdehyde and protein carbonyl levels by 34.5% and 12.0% respectively compared with thè control. In vivo, MEMO increased (P<0.05) superoxide dismutase and calai ase activities by 408.0% and 295.0% respectively. Taken together, this study demonstrates that MEMO exhibits antioxidant, radicai scavenging and enhancement of enzymatic antioxidant capacity and as such could intervene in toxicological processes mediated by free radicai mechanisms.Item ANTIMALARIAL AND ANTITUBERCULAR ACTIVITIES OF CRUDE METHANOL EXTRACT AND FRACTIONS OF THE BULB OF CRINUM JAGUS ( Linn.)(2015-02) KOLAWOLE, ADEBOLA OLAYEMICrinum jagus is a medicinal plant used traditionally to treat tuberculosis, malaria and other bacterial infections. However, there are limited documented scientific studies to substantiate the use of this plant. Due to increase in resistance to malaria and tuberculosis drugs, the need for the development of other drugs is pertinent. This study was designed to determine the pharmacological activities of extract and fractions of Crinum jagus. Methanol extract of C. jagus obtained by soxhlet extraction was subjected to phytochemical analysis and fractionated using column chromatography. Antitubercular and antimicrobial activities of the extract and its fractions were evaluated against isolates of Mycobacterium tuberculosis and selected microorganisms using the disc and agar diffusion methods. Antimalarial activity was assessed in vivo using Rane’s test in Plasmodium berghei infected mice (n = 80 in 10 groups) treated orally with tween 80 (control), 10, 25, 50 and 75 mg/kg of extract and its fractions at 10 mg/kg respectively, while chloroquine (10 mg/kg) and arteether (3 mg/kg) groups served as positive controls. Anti-inflammatory potential was assessed in rats using carrageenan-induced paw inflammatory model. In vitro antioxidant potentials were determined spectrophotometrically using 1,1-diphenyl-2-picryl hydrazyl (DPPH), hydroxyl radical scavenging activities, Total Flavonoids Contents (TFC) and Phenolic Contents (TPC) Antioxidant indices- Superoxide dismutase (SOD) and Catalase (CAT) activities and levels of Malondialdehyde (MDA) and reduced Glutathione (GSH) were determined by spectrophotometry. Aspartate (AST) and Alanine (ALT) amino transferases and Alkaline Phosphatase (ALP) were estimated spectrophotometrically. Data were analysed by Student’s t test at p = 0.05. Phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols and steroids in the crude extract. The extract and its fractions (F1, F2 and F3) showed a concentration- dependent inhibition of Mycobacterium tuberculosis, with F1 having the lowest IC50of : 0.22mg/mL relative to rifampicin (IC50 : 0.19mg/mL) and isoniazid (0.23mg/mL). The extract at 10, 25, 50, 75 mg/kg and F1, F2 and F3 at 10 mg/kg suppressed parasitaemia in Plasmodium berghei infected mice by 70.0, 76.0, 79.0, 87.0% and 89.0, 76.0, 78.0% respectively relative to chloroquine (100%) and arteether (89.0%). The extract at 10, 25, 50, 75 mg/kg and F1, F2 and F3 at 10 mg/kg inhibited oedema in rat paws by 26.0, 30.0, 32.0, 66.0% and 80.0, 25.0, 52.0% UNIVERSITY OF IBADAN LIBRARY iii respectively when compared with indomethacin (95.0%). The extract and its fractions significantly scavenged DPPH and hydroxyl radical in vitro. The TPC and TFC of extract, F1, F2 and F3 at 500 μg/ml were 0.310, 0.460, 0.240, 0.380 μg/mg and 0.523, 0.864, 0.396, 0.643 μg/g respectively. The extract and its fractions significantly reduced MDA level while GSH, SOD and CAT levels were increased. Activities of AST, ALT and ALP were significantly increased at 50 and 75 mg/kg body weight of extract . Crinum jagus exhibited antitubercular, antimalarial and anti-inflammatory activities via scavenging of radicals and antioxidative mechanism. This indicates a promising potential of the plant for drug development. Keywords: Crinum jagus, antituberculosis, antimalarial, antioxidant. Word Count: 471 .