STUDIES ON CADMIUM TOXICITY IN RAT TISSUES

Abstract

The presence of toxic levels of cadmium in the ecosystem has been increasing due to more and more industrial and agricultural use. Though several reports have appeared on renal damage, testicular necrosis and hepatotoxicity, the effect of cadmium on subcellular organelles such as mitochondria has been limited to uncoupling of oxidative phosphorylation and inhibition of substrate utilization as well as oxygen uptake. The present study is aimed at studying the in vivo effects of cadmium on citrate synthase and succinic dehydrogenase activity of citric acid cycle enzymes and cytochrome C oxidase activity of electron transport chain as well as morphological changes induced by cadmium in tissues of liver, kidney, testis and lung.

Male rats (Charles River) are exposed to single dose of cadmium by inhalation (850 ug Cd/m3 for two hours), intraperitoneal injection (3 mg Cd/kg body weight) and oral administration (25 mg Cd/kg body weight). Standard spectrophotometric methods are used in estimating the enzyme activities at various tine periods ranging from 24 to 144 hours after sodium administration by various routes. In addition, sodium accumulation and morphological changes in liver, kidney, testis and lung after cadmium administration are studied. In the inhalation series, lung mitochondrial enzymes are most affected; the citrate syntheses activity is decreased by 31%, the succinic dehydrogenase by 40% and the cytochrome C oxidase by 40% at 144 hours. In liver, kidney and testis, the succinic dehydrogenase and cyto¬chrome C oxidase activity is decreased while the citrate synthase activity is increased. Intraperitoneal and oral administration of cadmium decreased the mitochondrial enzyme activities in all the tissues studied, but predominantly in kidney and testis. In kidney, the citrate synthase activity is decreased by 12%, the succinic dehydrogenase by 14% and cytochrome C oxidase by 49% at 144 hours after cadmium injection. In testis, the citrate synthase activity is decreased by 65%, the succinic dehydrogenase by 23% and the cytochrome C oxidase by 51% at 24 hours after cadmium injection. Liver and kidney are the major organs accumulating cadmium after various routes of cadmium administration. Following inhalation exposure, large amount of cadmium is initially deposited in lung.

Histologically, striking changes are observed in lung following inhalation exposure. The alveolar septa are thick and the alveoli are lined by cuboidal cells. Destruction of testis is seen with oral and intraperitoneal administration of cadmium. Renal changes include increased glo¬merular space and apical vacuolation of the proximal tubule cells. These studies show that cadmium affects the tricarbo¬xylic acid cycle especially the succinic dehydrogenase activity. The decreased in this enzyme activity probably limits the transfer of reducing equivalents to the electron transport chain, resulting in inhibition of oxidative pho-sphorylation and substrate utilization. These studies are of significance in understanding the cadmium toxicity in relation to energy metabolism.