VITAMIN-E PREVENTS ENDOTHELIAL INJURY ASSOCIATED WITH CISPLATIN INJECTION INTO THE SUPERIOR MESENTERIC-ARTERY OF RATS

To clarify the pathogenesis of the vascular injury caused by the admin istration of anti-neoplastic drugs, cisplatin with lipiodol was infuse d into the superior mesenteric artery of rats. Morphological and bioch emical changes in the vascular wall and the prophylactic effects of vi tamin E were examined 4 days after administration. In the cisplatin-tr eated group, but not in the other groups, severe endothelial injury, s uch as vacuolation, subendothelial edema, and destruction of the inter nal elastic membrane, was observed. Superoxide dismutase, a potent sca venger of the superoxide anion, was markedly lower in the cisplatin gr oup, and Na/K-ATPase, a marker of the plasma membrane, was also low in this group. These morphological changes were minimal, and enzyme acti vity was higher in the vitamin E-treated group than in the cisplatin-t reated group. These findings indicate that endothelial injury after ci splatin administration could be caused by free radical-induced lipid p eroxidation of the membrane system, and that such injury may be preven ted by the co-administration of vitamin E.