Mercuric chloride toxicity in rat liver mitochondria and isolated hepatocytes

The effects of mercuric chloride on isolated rat liver mitochondria and freshly isolated rat hepatocytes were investigated. Mercuric chloride (in the μM range) depresses state 3 respiration, suggesting a strong effect at the level of the phosphorylation system. It also stimulates state 4 respiration and decreases mitochondrial membrane potential, suggesting an uncoupling action. In isolated hepatocytes, mercuric chloride causes a dose- and time-dependent cell death, accompanied by depletion of intracellular glutathione. Furthermore, mercuric chloride decreases intracellular ATP and ADP levels simultaneously with increasing AMP concentration, indicating fast hydrolysis of ATP without adequate rephosphorylation. From this study we can conclude that the bioenergetic lesion promoted by mercuric chloride seems to be sufficient to explain lethal hepatocyte injury.