Advertisement

Heart and Vessels

, Volume 10, Issue 4, pp 178–184 | Cite as

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

  • Hiroyuki Ito
  • Tatsumasa Okafuji
  • Tsuneyuki Suzuki
Originals

Summary

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.

Key words

Endothelial cell Free radical Superoxide dismutase Lipid peroxidation Vitamin E 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Konno T, Maeda H, Iwai E, Tashiro S, Maki S, Morinaga T, Mochinaga M, Hiraoka T, Yokoyama T (1983) Effect of arterial administration of high molecular weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma; a preliminary report. Eur J Cancer Clin Oncol 19:1053–1065Google Scholar
  2. 2.
    Konno T, Maeda H, Iwai K, Maki S, Tashiro S, Uchida M, Miyauchi Y (1984) Selective targeting of anticancer drugs and simultaneous image enhancement in solid tumors by arterially administered lipid contrast medium. Cancer 54:2367–2374Google Scholar
  3. 3.
    İçli F, Karaoguz H, Dinçol D, Demirkazki A, Gunel N, Karaoguz R (1993) Severe vascular toxicity associated with cisplatin-based chemotherapy. Cancer 72:587–593Google Scholar
  4. 4.
    Harrell RM, Bibley R, Vogelzang NJ (1982) Renal vascular lesions after chemotherapy with vinblastin, bleomycin, and cisplatin. Am J Med 73:429–433Google Scholar
  5. 5.
    Vogelzang NJ, Torkelson JL, Kennedy BJ (1985) Hypomagnesemia, renal dysfunction, and Raynaud's phenomenon in patients treated with cisplatin, vinblastin, and bleomycin. Cancer 56:2765–2770Google Scholar
  6. 6.
    Doll DC, List AF, Greco FA, Hainsworth JD, Hande KR, Johnson DH (1986) Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumor of the testis. Ann Intern Med 105:48–51Google Scholar
  7. 7.
    Ito H, Torii M, Suzuki T (1992) Myocardial vulnerability in cardiac hypertrophy:Comparison of hypertensive and normotensive rat drug-induced myocardial changes. In:Sassard J (ed) Genetic hypertension. Colloque INSERM, vol 218, John Libbey Eurotext, Montrouge pp 257–259Google Scholar
  8. 8.
    Torii M, Ito H, Suzuki T (1992) Lipid peroxidation and myocardial vulnerability in hypertrophied SHR myocardium. Exp Mol Pathol 57:29–38Google Scholar
  9. 9.
    Torii M, Inoue S, Matsushima S, Fuji S, Maruyama T, Muraoka Y, Ito H (1994) Increased sarcolemmal permeability in cardiomyopathy in hypertrophied SHR myocardium. J Toxicol Pathol 7:191–198Google Scholar
  10. 10.
    Ōyanagui Y (1984) Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal Biochem 142:290–296Google Scholar
  11. 11.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  12. 12.
    Lamers JMJ, Stinis JT (1981) An electrogenic Na/Ca antiporter in addition to the Ca pump in cardiac sarcolemma. Biochim Biophys Acta 640:521–534Google Scholar
  13. 13.
    Song CS, Bodansky O (1967) Subcellular localization and properties of 5′-nucleotidase in the rat liver. J Biol Chem 242:694–699Google Scholar
  14. 14.
    Ito H (1989) Pathophysiological changes of the membrane system of the arterial smooth muscle cells. In: Kwan CY (ed) Membrane abnormalities in hypertension, vol II. CRC, Boca Raton, pp 1–21Google Scholar
  15. 15.
    Ross R (1986) The pathogenesis of atherosclerosis — an update. N Engl J Med 314:488–500Google Scholar
  16. 16.
    Schilsky RL, Anderson T (1979) Hypomagnesemia and renal magnesium wasting in patients receiving cisplatin. Ann Intern Med 90:929–931Google Scholar
  17. 17.
    Goldhirsch A, Joss R, Markwalder TM, Studer H, Bruner K (1983) Acute cerebrovascular accident after treatment with cisplatin and methylprednisolone. Oncology 40:344–345Google Scholar
  18. 18.
    Licciardello JTW, Moake JL, Ruddy CK, Karp DD, Hong WK (1985) Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy. Oncology 42:296–300Google Scholar
  19. 19.
    Tappel AL (1973) Lipid peroxidation damage to cell components. Fed Proc 32:1870–1874Google Scholar
  20. 20.
    Olson RD, Mushlin PS (1990) Doxorubicin cardiotoxicity:Analysis of prevailing hypothesis. FASEB J 4:3076–3086Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Hiroyuki Ito
    • 1
  • Tatsumasa Okafuji
    • 2
  • Tsuneyuki Suzuki
    • 3
  1. 1.Division of Pathology, Research Institute of HypertensionKinki University School of MedicineOsakaJapan
  2. 2.Department of RadiologyKinki University School of MedicineOsakaJapan
  3. 3.Department of PathologyKinki University School of MedicineOsakaJapan

Personalised recommendations