Biochemical effects of dithiolthiones

Abstract

Administration of dithiolthiones to mice in single intragastric doses (2-4 mmol/kg body weight) or in the diet (0.5% for 14 days), and to rats in the diet (0.1% for 14 days) was found to increase glutathione levels and the activities of a number of enzymes in various tissues including the liver and lung. The enzymes affected were glutathione transferases (with chlorodinitrobenzene or dichloronitrobenzene), quinone and glutathione reductase, and glucose-6-phosphate and 6-phosphogluconate dehydrogenase, all of which are involved directly or indirectly in the detoxication of xenobiotics, including carcinogens. The dithiolthiones tested in mice were oltipraz, ADT, 116L and 129L, and in rats, oltipraz. Intragastric administration of dithiolthiones (oltipraz, ADT or 116L; two doses each of 1 g/kg body weight) did not increase glutathione levels or enzyme activities in murine mammary adenocarcinoma transplants. Increases in glutathione levels and enzyme activities similar to those found with dithiolthiones were observed when a semi-synthetic diet containing 10-40% lyophilized cabbage was fed to mice for 30 days. Dithiolthiones that are present in cabbage may play a role in the protective actions of diets high in vegetables against the toxic actions of xenobiotics. The biochemical effects of dithiolthiones reported here may account for the protective actions of these compounds.