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dc.contributor.authorOTUECHERE, C. A.
dc.date.accessioned2019-03-26T12:04:02Z
dc.date.accessioned2019-10-04T10:01:00Z
dc.date.available2019-03-26T12:04:02Z
dc.date.available2019-10-04T10:01:00Z
dc.date.issued2017-05
dc.identifier.urihttps://library.adhl.africa/handle/123456789/12269
dc.descriptionA Thesis in the Department of Biochemistry submitted to the Faculty of Basic Medical Sciences in partial fulfillment of the requirements for the Degree of Doctor of Philosophy of the University of Ibadan, Nigeria.en_US
dc.description.abstractOne of the probable causes of liver diseases is exposure to environmental chemicals. Agrochemicals containing propanil are known to induce hepatic toxicity. Pterocarpus mildbraedii leaf is used in traditional medicine to treat various disorders without scientific justification. This study was designed to investigate the protective tole of extract of Pterocarpus mildbraedii against propanii-induced hepatotoxicity in rats. Pterocarpus mildbraedii leaves, purchased from Oyingbo market, Lagos Stata, were authenticated at the University of Lagos Herbarium (LUT/5913). Powdered leaf was extracted in soxhlet, using dichloromethane:method (1:1), to yield crude extracts of Pterocarpus mildbraedii (PME). Sixty-four male Wistar rats (130-160 g), comprising of eight groups (n=8) were used for these experiments. Rats were treated orally with normal saline (control), PME (100mg/kg) PME (200mg/kg), PME (400mg/kg), propanil (200mg/kg), PME (100mg/kg) + propanil (200mg/kg), PME (200mg/kg) + propanil (200mg/kg) and PME (400mg/kg) + propanil (200mg/kg) for seven consecutive days. Hepatic tissues and serum were assayed for markers of hepatic damage, oxidative stress, inflammation, and apoptosis. Aspartase aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin (BIL), superoxide dismutase (SOD), catalase (CAT), redused glutathione (GSH), malondiadehyde (MDA), myeloperoxidase (MPO) and nitric oxide (NO) were assayed by spectrophotometry. Inducible Nitri Oxide Synthase (iNOS), Cyclooxygenase-2 (COX-2), Nuclear factor kappa B (NF-kB), Caspase 3, cASPASE 9, Bax, Bcl-2 expressions were measured using immunohistochemistry. Tumour supressor p53, Bcl-2 antagonist of cell death (Bad), NF-kB, inhibitor of total nuclear factor- KAPPA Bα(1kBα), stress activated protein kinase/C jun NH₂-terminal kinase (SAPK/JNK), p38 mitogen-activated protein kinase (p38) and signal transducer and activator of transcription 3 (STAT 3) were assessed by ELISA. Histopathology of liver was determined by microscopy and apoptosis by TUNEL assay. Data were analysed using ANOVA at α0.05. The yield of PME was 41.9%. Administration of propanil significantly increased AST (132.10±6.32 U/L), LDH (85.70±6.60 U/L), BIL (1.15±0.16 mg/dL), SOD (0.97±0.05 U/mg protein), MDA (1.03±0.08 ugMDA/mg protein), MPO (4.98±0.12 Umol/min/mg protein) and NO (0.38 umol/mg protein) relative to control (115.90 ± 8.65, 32.84±9.39, 115±0.16, 0.38±0.01, 0.40±0.11, 2.47±0.10 and 0.19 ±0.05, respectively). Pre-treatment of propanil-exposed rats with (200 mg/kg) significantly decreased LDH (83%), BIL (50%), SOD (50.5%), MDA (33.1%), MPO (63.3%) and NO (59.5%). Further, propanil administration increased the levels of GSH (2.98±0.24 ug/mg protein) and CAT (52.7±0.24 umol H₂0₂ consumed/min/g tissue) when compared with the controls (2.04±0.09 and 51.00±0.51). However, intervention with PME restored these serum biochemical indices and antioxidant parameters back to normal values. Expressions of iNOS, COX-2, NF kB, Caspase 3, Caspase 9 and Bax were higher in the propanil group relative to control. Levels of signaling mediators p38 (81.28±7.70), STAT 3 (88.80±4.40) and NF-kB (72.76± 5.30) were lower, while SAPK (125.39±9.30), 1kBα (115.83±5.60) and Bad (112.48±4.70) were higher in propanil-treated rats relative to control value set at 100. TUNEL-positive nuclei and severe periportal fibrosis were observed in tissues following propanil exposure. However, pre-treatment with PME significantly attenuated the observed propanil induced inflammation and apoptosis. Pterocarpus mildbraedii extract protected against propanil-induced hepatotoxicity via mechanisms that involved its antioxidant, anti-inflammatory and anti-apopiotic properties.en_US
dc.language.isoenen_US
dc.subjectPterocarpus mildbraediien_US
dc.subjectPropanilen_US
dc.subjectHepatotoxityen_US
dc.subjectApoptosisen_US
dc.subjectAnti-inflammatoryen_US
dc.titlePROTECTIVE EFFECT OF Pterocarpus mildbraedii HARMS EXTRACT ON PROPANIL-INDUCED HEPATOTOXICITY AND ALTERATIONS IN APOPTOTIC RELATED PROTEINS IN WISTAR RATSen_US
dc.typeThesisen_US


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