Studies on tissue distribution of glutathione and on activities of glutathione-related enzymes after carbon tetrachloride-induced liver injury.

After an initial decrease following CCl4-application (1.0 ml/kg bodyweight, i.p.), in the liver of male Wistar rats, values of reduced glutathione (GSH) are at a maximum 6 and 12 h after treatment. Oxidized glutathione (GSSG) increases up to 24 h after intoxication. Malondialdehyde (MDA) is at a low level, when GSH is high. Glutathione peroxidase has a clear initial increase of activity, but otherwise shows only slight deviations from control values. Cytosolic and microsomal glutathione-S-transferases reach minimum values at 6 and 12 h, respectively. The histochemical demonstration of GSH reveals an uneven distribution in the liver lobule, with higher amounts of reaction products in the periphery. With increasing time after intoxication the typical lobular distribution pattern changes and the accumulation of GSH reaction products becomes patchy. Other parts, however, remain rather normal. 12 h after intoxication most of the hepatic lobules are relatively free of GSH, while the content of the central venules and sublobular veins is strongly stained. Lipid histochemistry shows a fat accumulation already 3 h after CCl4. Central lobular cells are particularly affected. Biochemical and histochemical results are discussed with respect to the regional differences.