Subcellular toxicity of low level cadmium in rats: Effect on cytochrome c oxidase

Abstract

The in vivo effect of cadmium (Cd) with or without prior administration of L-cysteine (Cys) or diethylmaleate (DEM) on hepatic and renal cytochrome c oxidase (Cyt- c-Ox), essential metals and mitochondrial thiols was investigated. Male Sprague—Dawley rats were given 25 μg Cd/kg (as Cd acetate) orally 5 times a week for 6 weeks. Different groups of animals additionally received either Cys (500 mg/kg per day, p.o.) or DEM (0.85 mg/kg, i.p.) by multiple administration. Parameters were determined 1 day after the last gavage. Cadmium decreased the activity of Cyt- c-Ox in mitochondria of livers but not in those of kidneys. Copper in both tissue and mitochondria were unaffected whereas hepatic tissue iron decreased by 50% upon Cd gavage. Cysteine pretreatment increased hepatic and especially renal mitochondrial Cd, but diminished the Cd effect on Cyt- c-Ox and increased hepatic tissue iron. Both DEM and DEM/Cd treatment decreased Cyt- c-Ox by 50% in liver but not in kidneys. Metallothionein was not significantly altered by either treatment. Considering data from all the experimental groups Cyt- c-Ox activity seems to be related rather to the amount of protein thiols than to either copper or iron in hepatic mitochondria. The data demonstrate the high susceptibility of hepatic vs. renal mitochondria and suggest the involvement of thiols in Cyt- c-Ox activity.