MERCURIC-CHLORIDE TOXICITY IN RAT-LIVER MITOCHONDRIA AND ISOLATED HEPATOCYTES

The effects of mercuric chloride on isolated rat liver mitochondria an d freshly isolated rat hepatocytes were investigated. Mercuric chlorid e (in the mu M range) depresses state 3 respiration, suggesting a stro ng effect at the level of the phosphorylation system. It also stimulat es state 4 respiration and decreases mitochondrial membrane potential, suggesting an uncoupling action. In isolated hepatocytes, mercuric ch loride causes a dose- and time-dependent cell death, accompanied by de pletion of intracellular glutathione. Furthermore, mercuric chloride d ecreases intracellular ATP ana ADP levels simultaneously with increasi ng AMP concentration, indicating fast hydrolysis of ATP without adequa te rephosphorylation. From this study we can conclude that the bioener getic lesion promoted by mercuric chloride seems to be sufficient to e xplain lethal hepatocyte injury. (C) 1997 Elsevier Science B.V.