Heavy Metal-Induced Changes in the Glutathione Levels and Glutathione Reductase/Glutathione S-Transferase Activities in the Liver of Male Mice

Abstract

Glutathione S-transferases catalyze the metabolism of reactive substances of exogenous or endogenous origin and are involved in inactivation processes of xenobiotics and their metabolites. The present study aims at investigating the influence of heavy metals on the hepatic level of reduced glutathione (GSH), glutathione S-transferase, and glutathione reductase activities in the liver of male mice after single-dose (1 and 24 h) and repeated-dose treatments (three consecutive days). The hepatic level of GSH was depleted after single-dose treatments with cadmium chloride, mercuric chloride, cobalt chloride, cesium chloride, lead acetate, and silver nitrate, and percentage of GSH depletion was greater still after the repeated-dose treatments. Nickel chloride, on the other hand, did not cause any change in the level of GS H after any period of treatment. Glutathione reductase activity was increased 24 hours after treatment with cadmium chloride, mercuric chloride, lead acetate, and silver nitrate, whereas cobalt chloride decreased such activity after repeated doses. With the exception of cadmium chloride, glutathione S-transferase activity was significantly decreased 24 hours after a single-dose treatment with all of the tested heavy metals. Such alterations in the activities of phase II drug-metabolizing enzymes as a result of heavy metal treatment may change the hepatic capacity for the detoxification of many toxic compounds from endogenous or exogenous sources.