DSpace Collection: Dissertations in Biochemistry

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2025-06-03T11:39:23Z

Title: library Authors: Okon, Bayo

EFFECTS OF METHANOL EXTRACT OF Artocarpus altilis (BREADFRUIT) ON ATHEROGENIC INDICES AND REDOX STATUS OF CELLULAR SYSTEM OF HYPERCHOLESTEROLEMIC RATS

2019-04-29T10:00:53Z

Title: EFFECTS OF METHANOL EXTRACT OF Artocarpus altilis (BREADFRUIT) ON ATHEROGENIC INDICES AND REDOX STATUS OF CELLULAR SYSTEM OF HYPERCHOLESTEROLEMIC RATS Authors: AKANNI, O. O. Abstract: Hypercholesterolemia is a dominant risk factor for the development of cardiovascular diseases and has become a growing problem globally. Pharmacological interventions for the treatment of hypercholesterolemia involve the use of fibrates, bile acid sequestrants and statins. Due to high prevalence of adverse effects of these drugs, the quest for natural products with hypolipidemic potential is warranted. Artocarpus altilis (Breadfruit) is used locally in the treatment of hypertension. This study was designed to evaluate the effects of Methanol Extract of Artocarpus altilis (MEAA) on atherogenic indices and redox status of rats fed with dietary cholesterol. Studies on MEAA were conducted to determine its free radical scavenging potential. The 2,2-diphenyI-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydrogen peroxide (H₂O₂) and hydroxyl (OH) radicals scavenging effects of MEAA were determined by uv- spectrophotometry. Thirty-five adult male rats (150-200g) were divided into 7 groups of 5 rats each and treated orally with corn oil (control), dietary cholesterol (30mg/0.3mL), MEAA (100mg/kg)+ cholesterol, MEAA (200mg/kg)+cholesterol, questran (0.26g/kg)+cholesterol, questran alone (0.26g/kg) and MEAA alone (200mg/kg) for nine consecutive weeks. Lipid profile - Total Cholesterol (TC), Triglycerides, Low Density Lipoprotein- cholesterol (LDL-C) and High Density Lipoprotein-Cholesterol (LDL-C) were determined spectrophotometrically. Liver function enzymes - Aspartate and Alanine Aminotransferases (AST and ALT) and lactate dehydrogenase (LDH) were assayed by spectrophotometric technique. Antioxidant parameters - reduced glutathione (GSH), glutathione-s-transferase (GST), glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD) and lipid peroxidation (LPO) were estimated by spectroflorometry. Data were analysed using ANOVA and Student's t-test at p=0.05. The methanol extract of Artocarpus altilis effectively scavenged DPPH and OH radicals with lC₅₀ of 593 ug/mL and 487 ug/mL respectively. MEAA significantly scavenged H₂O₂ and NO in a dose-dependent manner. High dietary cholesterol intake caused a significant increase in the levels of serum hepatic and cardiac TC by 110%, 70% and 85%; LDL-C by 79%, 82% and 176%, and TG by 68%, 96% and 62%, respectively. In hypercholesterolemic rats, the serum and cardiac HDL-C levels (150.4±32.5, 347.5±25.0 mg/dL) were significantly lower than the controls (242.1±29.6, 451.2±79.8 mg/dL). Treatment with MEAA (200mg/kg) significantly increased serum and cardiac HDL-C levels (228.5±16.7, 433.0±45.9 mg/dL respectively) relative to hypercholesterolemic. In hypercholesterolemic rats, the levels of LDH, ALT and AST (4890.5±87.6, 121.8 ±19.6 and 362.1±11.0 U/L respectively) and LPO (4.8±0.7 umolMDA/mg protein) were significantly increased relative to controls (1822.8±177.9, 52.1±7.7, 218.0±18.0 U/L) and 1.3±0.2 umoIMDA/mg protein respectively. In contrast, hepatic and cardiac SOD, CAT and GPx were significantly decreased in hypercholesterolemic rats. Treatment with MEAA (200mg/kg) significantly improved the lipid profile and antioxidant indices of hypercholesterolemic rats. The results for MEAA (200mg/kg) were similar with questran treated rats. Methanol extract Artocarpus altilis elicited hypolipidemic effect in hypercholesterolemic rats via mechanism that involves radicals scavenging activities. Description: A Dissertation submitted to the Department of Biochemistry, Faculty of Basic Medical Science in partial fulfillment of the requirements for the award of degree of Master of Philosophy, University of Ibadan, Nigeria.

ASSESSMENT OF Ca²⁺ ATPase ACTIVITY AND MARKERS OF OXIDATIVE STRESS IN INDIVIDUALS OCCUPATIONALLY EXPOSED TO LEAD

2019-04-29T09:59:38Z

Title: ASSESSMENT OF Ca²⁺ ATPase ACTIVITY AND MARKERS OF OXIDATIVE STRESS IN INDIVIDUALS OCCUPATIONALLY EXPOSED TO LEAD Authors: IMAH-HARRY, J. C. Abstract: Lead (Ph²⁺) is an environmental toxicant which causes serious occupational diseases that are of major public health significance. Lead intoxication may arise from acute or chronic exposure and may alter calcium homeostasis leading to oxidative stress within human system. There are conflicting reports on the effect of lead on the activities of Ca²⁺ ATPase and oxidative stress. The aim of this study was to purify calcium ATPase, assess Blood Lead Levels (BLL), evaluate the activity of endogenous antioxidant enzymes and the production of reactive oxygen species in the blood of workers occupationally-exposed to lead. Forty consenting occupationally-exposed subjects: Battery chargers (BC, n=20), Spray painters (SP, n=10) and Auto Mechanics (AM, n=10) and fifteen consenting occupationally- unexposed subjects (control) were recruited from lbadan municipality. All subjects were aged between 25 and 55 years and those exposed to lead for at least 10 years. Blood samples (20ml) were collected from all subjects into ethylene diamine tetra- acetic acid tubes. Calmodulin-deficient ghost membranes were prepared from the crytherocytes and Ca²⁺-ATPase activity was assayed spectrophotometrically in the absence and presence of calmodulin. The BLL, biochemical and hematological profiles viz total protein, albumin, cholesterol and C-reactive protein (C-RP), antioxidant biomarkers such as Superoxide Dismutase (SOD), Catalase (CAT). Reduced Glutathione (GSH), Malondialdehyde (MDA), Total Antioxidant status. Total Plasma Peroxide (TPP) and Oxidative Stress Index (OSI) were by assayed by spectrophotometric techniques. Data were analysed using student's t-test and ANOVA at p=0.05. The BLL in BC (51.5±18.8 ug/dL), SP (35.8±10.1 ug/dL), AM (10.6±2.5 ug/dL) were significantly higher relative to control (8.5±4.5 ug/dL). The Ca²⁺-ATPase activities in BC (0.3) ± 0.02 umol/mg/h), SP (0.4± 0.03 umol/mg/h) and AM (0.6 ± 0.02 umol/mg/h) was significantly reduced relative to control (0.9 ± 0.03 umol/mg/h), in the presence of calmodulin, basal ATPase activity was increased by 68.4% in BC, 67.8% in SP and 68.2% in AM relative to control. The C-RP levels were higher in BC (16.0±10.1mg/L). SP (11.3±5.8mg/L) and AM (6.0±2.7mg/L) compared to control (3.1±1.5 mg/L). Cholesterol levels increased significantly only in BC (192.7± 26.4mg/L) when compared to control (160.6±8.0mg/L). The levels of MDA were higher in all lead-exposed workers: BC (9.3±0.8 nM/ml), SP (8.1± 1.2 nM/ml) and AM (7.3±0.5 nM/ml) relative to control (5.1±0.8 nM/ml). The levels of the antioxidant markers: CAT (0.02 ±0.01, 0.03 ±0.00, 0.03 ± 0.00 umol H₂O₂), SOD (0.3± 0.24, 0.2± 0.17, 0.8± 0.30 SOD units) and GSH (51.0 ± 4.39, 42.5± 8.92, 38.2 ± 8.57 umol/g) respectively, were all significantly reduced in BC, SP and AM when compared to the controls. Catalytic activities of the erythrocyte membrane Ca²⁺-ATPase were reduced in subjects occupationally-exposed to lead. Lead toxicity may be due to oxidative damage of the plasma membrane and its interaction with the catalytic cycle and calcium transport mechanism of the pump. Description: A Dissertation in the Department of Biochemistry, Faculty of Basic Medical Sciences, submitted in partial fulfillment of the requirements for the award of the degree of Master of Philosophy in the Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.

EFFECTS OF THE LEAF DECOCTION OF MOMORDICA CHARANTIA (BITTER LEMON) ON MITOCHONDRIAL MEMBRANE PERMEABILITY TRANSITION PORE AND FERTILITY IN MALE ALBINO RATS

2019-04-29T10:09:41Z

Title: EFFECTS OF THE LEAF DECOCTION OF MOMORDICA CHARANTIA (BITTER LEMON) ON MITOCHONDRIAL MEMBRANE PERMEABILITY TRANSITION PORE AND FERTILITY IN MALE ALBINO RATS Authors: ODEWUSI, A. F. Abstract: Certain anti-cancer agents act by inducing the intrinsic pathway of apoptosis which is mediated by the release of cytochrome C when the Mitochrondial Membrane Pemeability Transition (MMPT) pore opens. Several studies have authenticated the use of Momordica charantia (M.charantia) in the treatment of diabetes, breast cancer, skin tumor and prostatic cancer. This study was therefore carried out to determine whether the decoction of M.charantia will induce the opening of MMPT pore and the consequence of this on other parameters such as liver function and male fertility. Different doses, 35, 45, 55 and 65mg/100g body weight of the aqueous decoction of the fresh leaves of M.charantia were orally administered to groups A, B, C and D of animals respectively, for 30 days. The control group was fed with only water and feed ad libitum. Opening of MMPT pore was assayed in Mannitol-Sucrose-HEPES (MSH) buffer (210mM Mannitol, 7mM Sucrose and 5mM HEPES). Three hundred micromolar CaCI2/mg mitrochondria were measured quantitatively at 540nm in a Beckman UV spectrophotometer, Hepatic injury was assessed histologically and by the levels of Alanine Transaminase (ALT), Aspartate Transaminase (AST), y-Glutamyl Transferase (GGT) and Alkaline Phosphatase (ALP) in serum. Epididymal sperm samples obtained from the animals wer analyzed for motility, viability, sperm counts and morphology. Results were statistically analyzed using student's t-test and ANOVA at 0.05 level of significance. There were significant increases in the extent to which the different doses of the decoction induced opening of the MMPT pore. Maximum induction (-A540 =0.309) was obtained at 55mg/100g bw, which translates to about 11-fold increase when compared with control value (A540 -0.029) though, the extent of pore induction decreased to about 9-fold (A540 -0.249) at 65mg/100g bw. Significant reduction in sperm motility relative to control was observed for all treated animals. Sperm counts were also significantly reduced in this order: Group D< Group C< Group B< Group A< control with values ranging from 82.00-+2.45x10 6 cells/ml (control) to 64.25 -+8.26x10 6 cells /ml (Group D). Likewise, significant reductions of 86.25 -+ 4.79%, 91.67-+2.89% and 88.75-+2.50% in percentage viability were observed in animals that received 45.55 and 65mg/100g bw of decoction respectively, compared with control (95.5-+1.73%). Morphological abnormalities of sperm above the proposed 10% (Group B=12.94%, Group C=13.84% and Group D=13.02%) were also observed in animals that received 45mg/100g bw and above. There were significant dose-dependent increases in ALP and GGT levels for all groups relative to the control. Dose-related toxic effects of orally admnistered leaf decoction of M.charantia was observed in albino rats and may be implicated in male infertility in individuals who rely on the decoction in treating various ailments. Description: A Dissertation in the Department of Biochemistry, submitted to the Faculty of Basic Medical Sciences in partial fulfillment of the requirements for the award of the degree of Master of Philosophy of the University of Ibadan, Nigeria.