Tetrathiomolybdate Protects Against Liver Injury from Acetaminophen in Mice

Acetaminophen toxicity has become a leading cause of both accidental and intentional poisoning, and is now the most common cause of acute liver failure in the United States. Acetaminophen poisoning is thus a significant burden on the health care system and a cause of considerable morbidity and mortality. Tetrathiomolybdate is a fast acting anticopper drug developed for Wilson’s disease. However, if copper levels are lowered with tetrathiomolybdate, anticancer effects are obtained both in animal models and human patients. Inhibition of angiogenic cytokines by tetrathiomolybdate is the hypothesized mechanism. Tetrathiomolybdate has also proven to be effective against organ damage in the bleomycin mouse model of pulmonary damage, and in concanavalin A and carbon tetrachloride models of liver damage. Again, the hypothesized mechanism is cytokine inhibition, in this case inhibition of profibrotic and proinflammatory Brewer-vol4,no3 1/10/70 8:05 PM Page 419