Carbon Tetrachloride-Induced Alteration of Glutathione S-Transferase in Rat Liver Cytosol and Plasma

Abstract

Effects of carbon tetrachloride (CCl4) administration on hepatic and plasma glutathione S-transferase (GST) activity were studied in rats under both acute and chronic phases. Intraperitoneal administration of CCl4 at a high dosage (1.2ml/kg) (acute group) resulted in a marked elevation of plasma GST activity (over 200-fold of the control level at 24h after the administration) that was accompanied by a decrease in hepatic GST activity. In contrast to the successive elevation of plasma GST activity which had not reached a plateau by even 24h, plasma GPT activity reached a maximum at 6h after CCl4 administration and thereafter decreased to under the control value. Results for substrate specificity of plasma GST suggested that the leakage of hepatic GST into plasma began with by type 1-2 GSTs mainly and continued with not only type 1-2 GSTs but also type 3-4 ones. Supporting this assumption, immunohistochemical analyses of hepatic GSTs showed that the leakage of the GSTs occurred at the centrilobular zone where type 1-2 GSTs were shown to localize dominantly in the normal rat liver. And the leakage developed time-dependently to the surrounding area where both types of GSTs were diffusely distributed. Typical massive cell necrosis also developed in the same region. On the other hand, in the group administered repeatedly with a low dosage (0.4ml/kg) (chronic group), drastic alteration of GST activity and also GST localization could not be observed. These results indicate that elevation of plasma GST activity parallels to quantitative and qualitative alteration of hepatic GSTs as well as the extent of the liver damage in the acute phase. Measurement of plasma GST activity may provide useful information to judge the extent of acute liver damage clinically.