Caspase 3 Gene Expression Profile in Carbon Tetrachloride (CCL4) Induced Hepatotoxicity in Wistar Rats against Hepatoprotective Effect of Azadiracthta indica

Abstract

Liver is the vital organ of metabolism and excretion. It is also an important target of the toxicity of xenobiotics and oxidative stress. The study was carried out to determine the expression profile of caspase-3 gene in carbon tetrachloride (CCl4) induced hepatotoxicity in wistar rats. Thiry-five (35) wistar rats were divided into seven groups of five rats each group were given varying treatments along with intraperitonial administration of CCl4. The effects of aqueous and methanolic leaf extracts of Azadirachta indica were determined by evaluating the liver function enzymes namely Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), and Total bilirubin (T. bil).  Histopathological changes induced on the liver was examined and Caspase-3 expression in the liver was determined by real time PCR. Results showed increased in levels of AST (24.6±3.79), ALT, ALP (438.6±46.19), and T.BIL in CCl4-intoxicated rats were restored towards normalization in rats treated with the aqueous and methanolic extracts in a dose-dependent manner the highest from ALP and the least in AST. Histopathological studies revealed that rats treated with high dose (150mg/kg) of aqueous and methanolic extracts showed maximum hepatoprotective effects by alleviating the serum enzymes level at 150mg/kg body weight. Results furthermore, showed that A. indica significantly (p < 0.05) decreased the level (0.07, 0.06, 0.08, 0.04, 0.05) of caspase-3 gene expression towards normal in rats administered with the aqueous, methanolic leaf extracts and silymarin respectively.  This reveals that the Caspase-3 gene, as the enzyme executing apoptosis were expressed in less amount while wistar rats were induced with CCl4. Thus, conferring the protective effects of the leaf extracts and silymarin.