Cannabis sativa exacerbates hepatic injury caused by acetaminophen or carbon tetrachloride in rats

Abstract

The effect of Cannabis sativa extract on acute liver injury caused by acetaminophen or carbon tetrachloride (CCl4) was studied in rats. Cannabis sativa was given at doses of 5 or 10 mg/kg (expressed as Δ9-tetrahydrocannabinol) once daily intraperitoneally (i.p.) for 2 days and simultaneously with acetaminophen or CCl4. Rats were killed 24 h after acetaminophen or CCl4 administration. Reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA) and nitric oxide (nitrite/nitrate) concentrations were measured in the liver. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were determined in serum. Hepatic injury was also determined via histological examination of liver sections. The administration of only cannabis for 2 days had no significant effect on serum liver enzymes or on the hepatic levels of GSH, MDA or nitric oxide. However, in rats intoxicated with acetaminophen, Cannabis sativa at 5 or 10 mg/kg resulted in a significant increase in serum GOT by 17.6% and 19.5%, respectively, compared with the acetaminophen control group. In the CCl4-induced acute liver injury, the levels of AST, ALT and ALP in serum were significantly elevated by Cannabis sativa extract in a dose-dependent manner by 23.7–29.1%, 14.4–21.3% and 17.6–22.1%, respectively. In both models of hepatic injury, Cannabis sativa resulted in a significant increase in the level of liver MDA and nitric oxide and a significant decrease in GSH compared with the corresponding acetaminophen or CCl4 control group. These changes were dose dependent. Histological examination showed an increase in centrilobular necrotic areas in acetaminophen or CCl4-treated rats administered with Cannabis sativa. Histochemical investigation revealed a decrease in intracellular protein contents caused by CCl4 or acetaminophen, and these were further decreased by Cannabis sativa. It is concluded that short-term administration of Cannabis sativa enhances acute hepatic damage caused by CCl4 or acetaminophen in rats.