HYPOLIPIDAEMIC, ANTIOXIDATIVE AND HEPATOPROTECTIVE EFFECTS OF Persea americana (Lauraceae) LEAF EXTRACTS IN RATS)
Résumé
Hyperlipidaemia and oxidative stress are important factors in the pathogenesis of chronic degenerative and inflammatory diseases. Persea americana (Lauraceae) has been widely used in ethnomedicine in the treatment of various ailments including, hypertension. This study evaluated the hypolipidaemic, antioxidative and hepatoprotective potentials of Aqueous Extract of P. americana (AEPA) and Methanolic Extract of P. americana (MEPA) respectively in rats. Hyperlipidaemia and hepatotoxicity were induced by feeding 4-week old male rats with high lipid diet containing cholesterol and cholic acid, and carbon tetrachloride (CCI4) respectively. Hyperlipidaemic rats were administered AEPA or MEPA orally at 10mg kg-1 body weight for 8 weeks while three groups of rats pre-treated with Reducdyn (R) (consisting of acetyl-homocysteine-thiolactone and cysteine) 100 mg and AEPA 100 or 200 mg kg/body weight were intoxicated with CCI4. Control rats received standard chow and water only. Hypolipidaemic and antioxidant effects of the extracts were assessed by determining the levels of plasma lipids, antioxidant enzymes and glutathione (GSH) respectively. The hepatoprotective effect of P. americana was evalualed by assay of liver enzymes, bilirubin and histopathology of the liver. Phytochemical constituents of the extracts were determined by qualitative analysis. Data were analysed using ANOVA. Administration of AEPA reduced total plasma cholesterol (T-CHOL.), low density lipoprotein cholesterol (LDL) and triglycerides (TG) by 8%, 39% and 35% respectively while MEPA lowered T-CHOL (4%) and LDL (20%), Plasma high density lipoprotein cholesterol (HDL) level was increased while the index of atherogenicity (L DL/HDL) was markedly reduced in the treated rats compared to the hyperlipidaemic control. The extracts lowered oxidative stress as shown by significant decline in plasma malondialdehyde (MDA) and increase in GSM. The extracts elicited an increase in the activities of catalase and superoxide dismutase (SOD) compared to the hyperlipidaemic control rats. Hepatoprotective effect of AEPA was indicated by significant decrease in total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the treated rats compared to the control. AEPA was substantially hepatoprotective against CCI4-induced liver damage at 100mg kg-1 body weight. The highest percentage protection was against AST (94%). Pre-treatment with 200 mg kg-1 body weight AEPA protected the rats against liver damage (AST, 127%; ALT, 74%; bilirubin, 106%). Pre-treatment with AEPA also lowered T- CHOL and TG while total protein concentration was restored. Administration of AEPA reversed the increases in the levels of MDA, GSH, catalase and SOD caused CCI4 intoxication. Leukocytes counts also increased significantly after pre-treatment with 100mg kg-1 body weight AEPA. Histopathological analysis of CCI4-intoxicated rats showed that AEPA reduced the severity of necrosis, cellular infiltration and fatty change in the liver. Hypolipidaemic, antioxidant, and hepatoprotective effects of P. americana were comparable to Reducdyn(R). Qualitative screening of the extracts indicated the presence of alkaloids, flavonoids, saponins, steroids, tannins and iriterpenoids. Leaf extracts of P. americana possess hypolipidaemic, antioxidant, and hepatoprotective effects which may be attributed to individual or combined action of the phytoconstituents. This may account for its use in traditional medicine and could be further exploited in the management of diseases associated with hyperlipidaemia.
Remarques
A 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.