COMPARATIVE-STUDIES ON THE TOXICITY OF MERCURY, CADMIUM, AND COPPER TOWARD THE ISOLATED-PERFUSED RAT-LIVER

The toxic effects of cadmium, mercury, and copper were compared over t he range 0.01, 0.03, and 0.1 mM using the isolated perfused rat liver preparation. All metals caused similar changes in various parameters u sed to describe general toxicity. Thus reductions in oxygen consumptio n, perfusion flow, and biliary secretion were found, while lactate deh ydrogenase release into the perfusate, as well as liver weight, increa sed also in a dose-dependent fashion. Each metal caused similar magnit udes of changes and exerted similar potency. Measurement of other para meters indicating more specific injury revealed a number of difference s. Although all metals reduced hepatic ATP concentration, mercury and cadmium were more potent than copper in this respect. Cadmium was the most potent at decreasing reduced glutathione levels. Mercury was most effective at increasing tissue calcium content, while copper was less so, and cadmium ineffective. Only copper significantly increased tiss ue malondialdehyde (MDA) content, while all metals increased its relea se into perfusate. Furthermore, whereas cadmium seemed the most potent metal in increasing MDA release, it was least efficacious, while copp er was the most. Antioxidants such as superoxide dismutase, catalase, and Trolox C only reduced cadmium's influence on MDA in perfusate; how ever, they did not affect cadmium's ability to alter most other parame ters of vitality. Albumin reversed the toxic effects of copper and mer cury, but not cadmium. While metal-induced reductions in perfusion Now accounted for some of the toxic effects of the metals investigated, t he results as a whole supported the suggestion that all metals exerted toxicity at the mitochondria, since ATP levels were reduced in a mann er that could nor be reproduced by perfusion flow reduction alone. Lip id peroxidation appears to play little role in determining toxicity in duced by any of these metals. Furthermore, albumin may play an importa nt physiological role in preventing hepatic injury that might otherwis e be induced through acute metal intoxication.