Redox state in liver mitochondria in acute copper sulfate poisoning

Abstract

A patient with acute copper sulfate poisoning was found to have maintained a relatively oxidized hepatic mitochondrial redox state in spite of his being in refractory shock. The mechanism underlying this unexpected clinical observation was investigated. The study involved the allocation of male Wistar rats into three groups; copper sulfate-treated (intraperitoneal injection), hemorrhagic shock, and control. Since the copper sulfate-treated rats developed severe hypovolemic shock, hypovolemia was induced in the hemorrhagic shock group to mimic the time course of blood pressure reduction in the copper sulfate-treated group. The control rats were injected intraperitoneally with a saline solution. The hepatic energy charge and the arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, of each group of rats was determined. The hepatic energy charge of the copper sulfate-treated rats decreased significantly, reflecting severe hypotension and copper sulfate-induced hepatic damage. This decrease was greater than that observed in the rats subjected to hemorrhagic shock. Despite the profound shock and the markedly decreased hepatic energy charge, the AKBR in copper sulfate-treated rats did not decrease compared with the control group, while the AKBR in rats with induced hemorrhagic shock did decrease significantly. These observations, together with in vitro studies, suggest that the relatively oxidized redox state of liver mitochondria in the copper sulfate-treated rats, notwithstanding the severe shock state of these animals, may be the result of direct oxidation of NADH by copper sulfate.