Liver mitochondria alterations in chloroform-treated Sprague-Dawley rats.

The formation of a chloroform adduct produced by the reaction of the oxidative chloroform metabolite phosgene with two molecules of phosphatidylethanolamine has been previously demonstrated in liver mitochondria of phenobarbital-pretreated Sprague-Dawley (SD) rats. The aim of our study was to assess the influence of chloroform adduct mitochondrial accumulation on the hepatic mitochondria morphology. Liver mitochondrial ultrastructural alterations were analyzed by electron microscopy in SD rats administered with increasing doses of chloroform. Variation in the morphology of mitochondria, consisting of an increase of intertwined organelles, only rarely seen in control specimens, was observed at the lowest chloroform dose (180 mg/kg). At higher doses, mitochondrial damage progressed with swelling of the organelles and formation of megamitochondria. These megamitochondria were characterized by a dilution of the matrix, and often membranous whorls were found inside the matrix. The two distinct forms of cell death, necrosis and apoptosis, were first observed at 300 mg/kg of chloroform. Our results suggest that the formation and the accumulation of a chloroform-modified phosphatidylethanolamine in mitochondria induce ultrastructural modifications of these organelles. In conclusion, mitochondria are involved in chloroform-induced hepatotoxicity.