Antioxidant Action of Malotilate on Prolonged Hepatic Injury Induced by Carbon Tetrachloride Alone or in Combination with Ethanol in Rat

사염화탄소 및 에탄올에 의해 유도된 만성간 손상에 미치는 말로틸레이트의 항산화 작용

To achieve a better understanding of antioxidant action manifested by malotilate, the dithiol malonates, we monitored the oxy radical-scavenging system against the chronic hepatic damage induced by $CCl_4$ alone or in combination with ethanol. Malotilate was given orally at a dose of 100 mg/kg/day and $CCl_4$ 1.5 ml/kg was injected subcutaneously twice a week for 4 weeks. In each group receiving ethanol, drinking water was replaced by 20% aqueous solution or glucose, isocaloric amounts of ethanol, as a control of ethanol was diluted in its drinking water. Each rat was killed as a starved state at 18 hours after the period of the experiment, four weeks. The results were summarized as follows: 1) Malotilate inhibited the rate of generation of superoxide radicals, the accumulation of lipoperoxides, and promoted the synthesis of glutathione in the liver. 2) Malotilate stimulated the enhancement of activity of superoxide dismutase in hepatic mitochondria. 3) Malotilate had no effects on the hepatic $H_2O_2$ contents. 4) Malotilate showed the increase of catalase activity in the liver poisoned with $CCl_4$, and also gave a tendency to increase it in the liver intoxicated with ethanol. Thus, our data suggested that the activation of hepatic antioxidant system in the presence of malotilate would play a role in protecting liver against the toxic effects of oxy radical and/or lipid peroxides under the hepatotoxic conditions induced by $CCl_4$ with or without ethanol. However, the effects of malotilate against the ethanol-induced hepatotoxicity appear to be insignificant.