Vitamin E prevents endothelial injury associated with cisplatin injection into the superior mesenteric artery of rats.

Abstract

To clarify the pathogenesis of the vascular injury caused by the administration of anti-neoplastic drugs, cisplatin with lipiodol was infused into the superior mesenteric artery of rats. Morphological and biochemical changes in the vascular wall and the prophylactic effects of vitamin E were examined 4 days after administration. In the cisplatin-treated group, but not in the other groups, severe endothelial injury, such as vacuolation, subendothelial edema, and destruction of the internal elastic membrane, was observed. Superoxide dismutase, a potent scavenger of the superoxide anion, was markedly lower in the cisplatin group, and Na/K-ATPase, a marker of the plasma membrane, was also low in this group. These morphological changes were minimal, and enzyme activity was higher in the vitamin E-treated group than in the cisplatin-treated group. These findings indicate that endothelial injury after cisplatin administration could be caused by free radical-induced lipid peroxidation of the membrane system, and that such injury may be prevented by the co-administration of vitamin E.