EVALUATION OF THE PROTECTIVE ROLE OF HESPERIDIN AGAINST ACETAMINOPHEN-INDUCED HEPATOTOXICITY IN ALBINO RATS

Abstract

Acetaminophen (APAP) is a very commonly used antipyretic analgesic drug. Over-dosage of acetaminophen has been reported to cause severe liver injury and is often fatal. The present study was designed to establish the protective role of hesperidin (HDN), a citrus bioflavonoid, on acetaminophen-induced oxidative stress and the resultant dysfunction in rat liver. The study was performed using forty adult male rats. They were allocated into four groups: Group (I) served as a control group. Group (II), received a single oral dose of 1 mg/kg b.w. of APAP. Group (GIII), received HDN 200mg/kg b.w. per os daily for ten days. Group (IV), received both HDN & APAP in the same previous doses and routes. On the 10th day of the experiment, all animals were sacrificed 2hr after the last dose of HDN. In association with APAP administration, the levels of serum total protein and albumin were reduced significantly indicating impaired protein synthesis in the liver. In addition, the activities of serum aspartate and alanine aminotransferases (AST & ALT) and alkaline phosphatase (ALP) were significantly elevated in APAP- treated group indicating liver dysfunction. Moreover, serum total cholesterol, triglycerides and low density lipoprotein (LDL) levels highly significant increases, while, marked decrease in the high density lipoprotein (HDL) was observed. Malondialdehyde (MDA) concentration was markedly increased reflecting increased lipid peroxidation, whereas, reduced glutathione (GSH) and superoxide dismutase (SOD) levels were significantly decreased. The histopathological study revealed that administration of APAP induced marked alterations in the liver tissue; these included severe hydropic degeneration, dilatation of the central veins and focal inflammatory mononuclear leukocytic infiltration in between degenerated hepatocytes. The portal areas were oedematous and were successfully infiltrated by inflammatory cells with severe dilatation and congestion of the branches of the portal veins. All these alterations were attributed to the APAP-induced oxidative stress. On the other hand, the administration of HDN plus APAP improved the biochemical and histological alterations by decreasing lipid profile and lipid oxidation and increasing GSH content and SOD activity as well as improving the liver tissue; these ensure the protective effect of HDN. This protective effect of HDN can be correlated to its antioxidant role.