Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants

Abstract

Glutathione S-transferases and glutathione play an important role in the detoxification of most toxic agents. In the present study, the protective effects of some antioxidants ( l-ascorbic acid (AA), vitamin E (VE) or garlic) on carbon tetrachloride-induced changes in the activity of alanine amino transferase (ALT), aspartate amino transferase (AST), glutathione S-transferase (GST), and the level of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were studied. The activities of ALT, and AST were assayed in plasma, whereas the activity of GST and the levels of GSH and TBARS were determined in the livers of rats. The current study included two experiments. In the first experiment, animals received single oral dose of CCl 4 (400 mg/kg body weight) after administration of AA (100 mg/kg b.w.), VE (100 mg/kg b.w.) or garlic (800 mg/kg b.w.) as single oral doses. In the second experiment, rats received repeated oral doses of antioxidants for 12 consecutive days followed by a single oral dose of CCl 4 on the 13th day and killed after that by 24 h. Treatment of male rats with CCl 4 significantly increased the activity of ALT and AST in plasma, and the levels of both GSH and TBARS in the liver. On the other hand, CCl 4 inhibited the activity of GST after single dose treatment. Single-dose treatments of rats with AA, VE or garlic prior to the administration of CCl 4 could not restore the alterations in the activity of ALT and AST caused by CCl 4 to the normal control level. However, repeated dose treatments with these agents restored such alterations to the normal level. We observed that VE is more effective than AA and garlic in restoring the inhibition of GST activity caused by CCl 4 to the normal level after single dose treatments. On the other hand, AA and VE are more effective than garlic in restoring the induced TBARS level caused by CCl 4 to the normal control level after repeated dose treatments. It has been observed that the tested antioxidants were able to antagonize the toxic effects of CCl 4, and such counteracting effects were more pronounced when they were administered as repeated doses prior to administration of CCl 4.