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 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.
Division of Pathology, Kinki University School of Medicine, Osaka, Japan.
H
H
Ito
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T
Okafuji
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T
Suzuki
D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D014810:Vitamin E; D013482:Superoxide Dismutase; D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase; D002945:Cisplatin