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Zinc acetate pretreatment ameliorates cisplatin-induced Sertoli cell dysfunction in Sprague-Dawley rats

  • Original Articles
  • Zinc Acetate, Cisplatin, Sertoli Cell Dysfunction
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Summary

The present study was undertaken to determine if prior administration of zinc acetate (ZnAc) or copper sulfate (CuSO4) could prevent pituitary, Leydig, or Sertoli cell dysfunction subsequent to cisplatin administration in adult Sprague-Dawley rats. Animals were given cisplatin at a dose of 2 mg/kg daily for 5 days, with or without the i.p. administration of ZnAc (6 mg/kg per day) or CuSO4 (5 mg/kg per day), beginning 5 days prior to and continuing through the administration of cisplatin. Control animals were given vehicle, ZnAc1, or CuSO4. Animals were sacrificed 1 week after the initial cisplatin injection. Cisplatin administration resulted in suppressed serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels as well as a 77% reduction in serum testosterone and an 82% reduction in testicular testosterone. The concomitant administration of either ZnAc or CuSO4 did not result in a significant difference relative to animals receiving cisplatin alone, although administration of both cations alone significantly reduced testicular testosterone content. Serum androgen-binding protein (ABP) was not significantly lowered in any treatment group. There was a marked reduction of 57% in testicular ABP content relative to control values subsequent to cisplatin administration. This reduction was partially prevented by ZnAc treatment; the testicular ABP concentration was only 15% lower than that in controls (not significant). Since the cisplatin-induced reduction in serum FSH was not altered by ZnAc pretreatment, we conclude that the near normalization of testicular ABP content may be evidence of improved Sertoli cell function. In contrast, cisplatin-induced decreases in the serum gonadotropins and testicular androgens were not lessened by pretreatment with either cation. Further studies may be warranted to determine whether ZnAc pretreatment has a beneficial effect on spermatogenesis during cisplatin treatment.

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References

  1. Berthelsen JG, Skakkebaek NE (1983) Gonadal function in men with testis cancer. Fertil Steril 39: 93–98

    Google Scholar 

  2. Chellman G, Shaikh ZA, Baggs RB, Diamond GL (1985) Resistance to cadmium-induced necrosis in testes of inbred mice: possible role of a metallothionein-like cadmium-binding protein. Toxicol Appl Pharmacol 79: 511–523

    Google Scholar 

  3. Corden BJ, Fine RL, Ozols RF, Collins JM (1985) Clinical pharmacology of high dose cisplatin. Cancer Chemother Pharmacol 14: 38–41

    Google Scholar 

  4. Guarino AM, Miller DS, Arnold ST (1979) Platinate toxicity: past, present and prospects. Cancer Treat Rep 63: 1475–1483

    Google Scholar 

  5. Gunn SA, Gould TC, Anderson WAD (1961) Hormonal control of zinc in mature rat testis. J Endocrinol 23: 37–43

    Google Scholar 

  6. Gunsalus GL, Musto NA, Bardin CW (1978) Immunoassay of androgen binding protein in blood: a new approach for study of the seminiferous tubule. Science 200: 65–67

    Google Scholar 

  7. Gunsalus GL, Larrea F, Musto NA, Becker RR, Mather JP, Bardin CW (1981) Androgen binding proteins as a marker for Sertoli cell function. J Steroid Biochem 15: 99–105

    Google Scholar 

  8. Huang HFS, Nieschlag E (1986) Suppression of the intratesticular testosterone is associated with quantitative changes in spermatogonial populations in intact adult rats. Endocrinology 118: 619–627

    Google Scholar 

  9. Levi J, Jacobs C, Kalman SM, McTigue M, Weiner JW (1980) Mechanism of cis-platinum nephrotoxicity: 1. Effects of sulfhydryl groups in rat kidneys. J Pharmacol Exp Ther 213: 545–550

    Google Scholar 

  10. Loehrer JP, Einhorn LH (1984) Cisplatin. Ann Int Med 100: 704–713

    Google Scholar 

  11. Maines MD, Mayer RD (1985) Inhibition of testicular cytochrome P-450-dependent steroid biosynthesis by cisplatinum. J Biol Chem 250: 6063–6068

    Google Scholar 

  12. Naganuma A, Satoh M, Imura N (1984) Effect of copper pretreatment on toxicity and antitumor activity of cis-diamminedichloroplatinum in mice. Res Commun Chem Pathol Pharmacol 46: 265–274

    Google Scholar 

  13. Naganuma A, Satoh M, Koyama Y, Imura N (1985) Protective effect of metallothionein inducing metals on lethal toxicity of cis-diamminedichloroplatinum in mice. Toxicol Lett 24: 203–207

    Google Scholar 

  14. Pogach L, Lee Y, Giglio W, Huang FHS (1985) Leydig cell dysfunction following cisplatin administration in Sprague Dawly rats (Abstract). American Federation for Clinical Research, Washington, DC

    Google Scholar 

  15. Pogach LM, Lee Y, Gould S, Giglio W, Meyenhofer M, Huang HFS (1989) Characterization of cisplatinum induced Sertoli cell dysfunction in rodents. Toxicol Appl Pharmacol (in press)

  16. Preece A (ed) (1972) A manual for histologic technicians. Little, Brown and Company, Boston

    Google Scholar 

  17. Roberts JJ (1982) Cisplatin. In: Pinedo HM (ed) Cancer chemotherapy. Excerpta Medica, Amsterdam, pp 95–117

    Google Scholar 

  18. Rosenberg B, VanCamp L, Krigas T (1965) Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205: 698–699

    Google Scholar 

  19. Sharma RP (1984) Cisplatinum: effect of zinc acetate pretreatment on cellular uptake and interactions with cytosolic ligands. Toxicology 32: 75–84

    Google Scholar 

  20. Sharma RP (1985) Interactions of cis-platinum with cellular zinc and copper in rat liver and kidney tissues. Pharmacol Res Commun 17: 197–210

    Google Scholar 

  21. Solecki TJ, Avia A, Bogden JD (1984) Effect of a chelating drug on balance and tissue distribution of four essential metals. Toxicology 31: 107–116

    Google Scholar 

  22. Taylor DM, Jones JD, Robins AB (1973) Metabolism of platinum 14C-ethylenediamine dichloride in the rat. Biochem Pharmacol 22: 831–839

    Google Scholar 

  23. Timm F, Schulz G (1966) Hoden und Schwermetalle. Histochemie 7: 15–27

    Google Scholar 

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Pogach, L.M., Lee, Y., Giglio, W. et al. Zinc acetate pretreatment ameliorates cisplatin-induced Sertoli cell dysfunction in Sprague-Dawley rats. Cancer Chemother. Pharmacol. 24, 177–180 (1989). https://doi.org/10.1007/BF00300239

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  • DOI: https://doi.org/10.1007/BF00300239

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