Comparative Studies on the Toxicity of Mercury, Cadmium, and Copper Toward the Isolated Perfused Rat Liver

Abstract

The toxic effects of cadmium, mercury, and copper were compared over the over range 0.01, 0.03, and 0.1 mM using the isolated perfused rat liver preparation. All metals caused similar changes in various parameters used to describe general toxicity. Thus reductions in oxygen consumption, perfusion flow, and biliary secretion were found, while lactate dehydrogenase release into the perfusate, as well as liver weight, increased also in a dose-dependent fashion. Each metal caused similar magnitudes of changes and exerted similar potency. Measurement of other parameters indicating more specific injury revealed a number of differences. 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 tissue malondialdehyde (MDA) content, while all metals increased its release into perfusate. Furthermore, whereas cadmium seemed the most potent metal in increasing MDA release, it was least efficacious, while copper was the most. Antioxidants such as superoxide dismutase, catalase, and Trolox C only reduced cadmium's influence on MDA in perfusate; however, they did not affect cadmium's ability to alter most other parameters of vitality. Albumin reversed the toxic effects of copper and mercury, but not cadmium. While metal-induced reductions in perfusion flow accounted for some of the toxic effects of the metals investigated, the results as a whole supported the suggestion that all metals exerted toxicity at the mitochondria, since ATP levels were reduced in a manner that could not be reproduced by perfusion flow reduction alone. Lipid peroxidation appears to play little role in determining toxicity induced by any of these metals. Furthermore, albumin may play an important physiological role in preventing hepatic injury that might otherwise be induced through acute metal intoxication.

Co-Exposure Effects of LPS with Various Aflatoxin B1 Doses in Isolated Perfused Rat Liver Model

“…In groups with LPS, similar to groups without LPS in time-dependent manner, levels of ALT and AST increased at AFB1 concentrations of 0.01, 0.1 and 1 ppm, that concentrations of 0.1 and 1ppm had statistically significant different with LPS group. Our finding is consistent with the most investigators finding about time course of enzyme changes in exposure with naproxen [15], copper and AFB1 [16][17][18], cadmium [19], vanadium [20] in perfused rat liver model.…”

Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes

“…Furthermore, lipid peroxidation increases mitochondrial and cellular permeability alterations, involving GSH [37,70] and calcium depletion [70]. These outcomes work together to create a continuous cycle where acceleration of the mitochondrial chain induces oxidative stress, lipid peroxidation and depletion of antioxidant defenses, which, in turn, diminish membrane permeability and accelerate the respiratory chain, thus generating more ROS.…”

Trolox enhances the anti-lymphoma effects of arsenic trioxide, while protecting against liver toxicity

“…This is the first study to report in vivo protective effects of trolox on arsenic-induced hepatotoxicity, although several studies have demonstrated its efficacy in preventing toxicity of other metals. 36 In addition, studies have shown that a trolox derivative (U-83836E) appeared to be beneficial in reducing lipid peroxidation products and in partially preventing the decrease in glutathione and antioxidant enzymes induced by methanol in liver, serum 37 and brains 38 of rats. Lower doses of trolox than used in the present study clearly reduced methylmercury-induced toxicity in rats.…”