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The effect of sodium thiosulfate on ototoxicity and pharmacokinetics after cisplatin treatment in guinea pigs

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Abstract

The effect of sodium thiosulfate (STS) on the pharmacokinetics and ototoxicity of cisplatin (CDDP) was investigated in guinea pigs. Animals received three intramuscular injections of 7.5 mg/kg CDDP separated by intervals of 5 days with or without STS (1,000 mg/kg) administered intraperitoneally immediately and 1 h after each injection of CDDP or 3 and 6 h later. When administered alone, CDDP caused total outer hair cell (OHC) loss in the basal and second turns of the cochlea. In the group administered CDDP and STS, damage to the OHCs was mild when STS was given concurrently, but was severe when STS was given 3 and 6 h later. Pharmacokinetics measured as free and total platinum (Pt) concentrations in plasma and total Pt concentration in perilymph was not affected after administration of STS with CDDP. These results suggest that an inactive Pt-thiosulfate complex is formed in plasma and is measured as a free Pt component which enters the perilymph via the blood-cochlear barrier. Two possible mechanisms are proposed by which STS reduces ototoxicity: entry of CDDP into target cells such as OHCs and striai marginal cells or binding to intracellular macromolecules of these cells is prevented.

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References

  1. Abe R, Akiyoshi T, Tsuji H, Baba T (1986) Protection of antiproliferative effect ofcis-diamminedichloroplatinum (II) by sodium thiosulfate. Cancer Chemother Pharmacol 18: 98–100

    Article  PubMed  CAS  Google Scholar 

  2. Abe R, Akiyoshi T, Koba F, Tsuji H, Baba T (1988) ‘Tworoute chemotherapy’ using intra-arterial cisplatin and intravenous sodium thiosulfate, its neutralizing agent, for hepatic malignancies. Eur J Cancer Clin Oncol 24: 1671–1674

    Article  PubMed  CAS  Google Scholar 

  3. Abe R, Akiyoshi T, Baba T (1990) ‘Two-route chemotherapy’ using cisplatin and its neutralizing agent, sodium thiosulfate, for intraperitoneal cancer. Oncology 47: 422–426

    PubMed  CAS  Google Scholar 

  4. Church MW, Kaltenbach JA, Blakley BW, Burgio DL (1995) The comparative effects of sodium thiosulfate, diethyldithiocarbamate, fosfomycin and WR-2721 on ameliorating cisplatin-induced ototoxicity. Hear Res 86: 195–203

    Article  PubMed  CAS  Google Scholar 

  5. Gandara DR, Wiebe VJ, Perez EA, Makuch RW, DeGregorio MW (1990) Cisplatin rescue therapy: experience with sodium thiosulfate, WR2721, and diethyldithiocarbamate. Crit Rev Oncol Hematol 10: 353–365

    Article  PubMed  CAS  Google Scholar 

  6. Goel R, Cleary SM, Horton C, Kirmani S, Abramson I, Kelly C, Howell SB (1989) Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin. J Natl Cancer Inst 81: 1552–1560

    Article  PubMed  CAS  Google Scholar 

  7. Guastalla JP, Vermorken JB, Wils JA, George M, Scotto V, Nooij M, Bokkel Huinnink WW ten, Dalesio O, Renard J (1994) Phase II trial for intraperitoneal cisplatin plus intravenous sodium thiosulphate in advanced ovarian carcinoma patients with minimal residual disease after cisplatin-based chemotherapy — a phase II study of the EORTC gynaecological cancer cooperative group. Eur J Cancer 30A: 45–49

    Article  PubMed  CAS  Google Scholar 

  8. Hanneman J, Baumann K (1990) Nephrotoxicity of cisplatin, carboplatin, and transplatin. Arch Toxicol 64: 393–400

    Article  Google Scholar 

  9. Howell SB, Pfeile CL, Wung WE, Olshen RA, Lucas WE, Yon JL, Green M (1982) Intraperitoneal cisplatin with systemic thiosulfate protection. Ann Intern Med 97: 845–851

    PubMed  CAS  Google Scholar 

  10. Howell SB, Pfeile CE, Wung WE, Olshen RA (1983) Intraperitonealcis-diamminedichloroplatinum with systemic thiosulfate protection. Cancer Res 43: 1426–1431

    PubMed  CAS  Google Scholar 

  11. Inoue M, Shimizu C, Shimizu H, Tanizawa O (1991) Neutralizing effect of sodium thiosulfate on antitumor efficacy of cisplatin for human carcinoma xenografts in nude mice. Gynecol Oncol 40: 34–37

    Article  PubMed  CAS  Google Scholar 

  12. Ishizawa M, Taniguchi S, Baba T (1981) Protection by sodium thiosulfate and thiourea against lethal toxicity ofcis-diamminedichloroplatinum (II) in bacteria and mice. Jpn J Pharmacol 31: 883–889

    Article  PubMed  CAS  Google Scholar 

  13. Iwamoto Y, Kawano T, Uozumi J, Aoki K, Baba T (1984) lsTwo-route chemotherapy” using high-dose ip cisplatin and iv sodium thiosulfate, its antidote, for peritoneally disseminated cancer in mice. Cancer Treat Rep 68: 1367–1373

    PubMed  CAS  Google Scholar 

  14. Iwamoto Y, Kawano T, Ishizawa M, Aoki K, Kuroiwa T, Baba T (1985) Inactivation ofcis-diamminedichloroplatinum (II) in blood and protection of its toxicity by sodium thiosulfate in rabbits. Cancer Chemother Pharmacol 15: 228–232

    Article  PubMed  CAS  Google Scholar 

  15. Laurell G, Engström B (1989) The ototoxic effect of cisplatin on guinea pigs in relation to dosage. Hear Res 38: 27–34

    Article  PubMed  CAS  Google Scholar 

  16. Litterst CL (1984) Cisplatinum: a review, with special references to cellular and molecular interactions. Agents Actions 15: 520–524

    Article  PubMed  CAS  Google Scholar 

  17. Loerer PJ, Einhoen LH (1984) Cisplatin, diagnosis and treatment. Ann Intern Med 100: 704–713

    Google Scholar 

  18. McAlpine D, Johnstone BM (1990) The ototoxic mechanism of cisplatin. Hear Res 47: 191–204

    Article  PubMed  CAS  Google Scholar 

  19. Neijt JP, Bokkel Huinink WW ten, Burg MEL van der, Oosterom AT, Willemse PHB, Vermorken JB, Lindert ACM van, Heintz APM, Aartsen E, Lent M van, Trimbos JB, Meijer AJ de (1991) Long-term survival in ovarian cancer. Eur J Cancer 27: 1367–1372

    Article  PubMed  CAS  Google Scholar 

  20. Otto WC, Brown RD, Gage-White L, Kupetz S, Anniko M, Penny JE, Henley CM (1988) Effects of cisplatin and thiosulfate upon auditory brainstem responses of guinea pigs. Hear Res 35: 79–86

    Article  PubMed  CAS  Google Scholar 

  21. Ozols RF, Corden BJ, Jacob J, Wesley MN, Ostchega Y, Young RC (1984) High-dose cisplatin in hypertonic saline. Ann Intern Med 100: 19–24

    PubMed  CAS  Google Scholar 

  22. Robbins KT, Storniolo AM, Kerber C, Seagren S, Berson A, Howell SB (1992) Rapid superselective high-dose cisplatin infusion for advanced head and neck malignancies. Head Neck 14: 364–371

    Article  PubMed  CAS  Google Scholar 

  23. Sagiyama K, Uozumi J, Aoki K, Baba T (1983) Efficacy of “two-route chemotherapy” using intra-arterial cisplatin and iv sodium thiosulfate, its antidote, in rat bladder tumor. Cancer Treat Rep 67: 567–572

    PubMed  CAS  Google Scholar 

  24. Saito T, Aran J-M (1994) X-ray microanalysis and ion microscopy of guinea pig cochlea and kidney after cisplatin treatment. ORL 56: 310–314

    PubMed  CAS  Google Scholar 

  25. Saito T, Aran J-M (1994) Comparative ototoxicity of cisplatin during acute and chronic treatment. ORL 56: 315–320

    Article  PubMed  CAS  Google Scholar 

  26. Saito T, Manabe Y, Honda N, Yamada T, Yamamoto T, Saito H (1995) Semiquantitative analysis by scanning electron microscopy of cochlear hair cell damage by ototoxic drugs. Scanning Microsc 9: 271–281

    PubMed  CAS  Google Scholar 

  27. Saito T, Manabe Y, Saito H (1995) Ototoxicity of the new platinum anticancer agent TRK-710 in comparison with cisplatin. ORL 57: 250–255

    PubMed  CAS  Google Scholar 

  28. Schweitzer VG (1993) Cisplatin-induced ototoxicity: the effect of pigmentation and inhibitory agents. Laryngoscope 103 [Suppl 59]: 1–52

    Article  PubMed  CAS  Google Scholar 

  29. Singh G (1989) A possible cellular mechanism of cisplatin-induced nephrotoxicity. Toxicology 58: 71–80

    Article  PubMed  CAS  Google Scholar 

  30. Smith IE, Talbot DC (1992) Cisplatin and its analogues in the treatment of advanced breast cancer: a review. Br J Cancer 65: 787–793

    PubMed  CAS  Google Scholar 

  31. Uozumi J, Sagiyama K, Aoki K, Iwamoto Y, Baba T (1983) Effectiveness of ‘two-route chemotherapy’, using cisplatin and its antidote, sodium thiosulfate, on lifespan of rats bearing metastatic liver tumors. Cancer Treat Rep 67: 1067–1074

    PubMed  CAS  Google Scholar 

  32. Uozumi J, Ishizawa M, Iwamoto Y, Baba T (1984) Sodium thiosulfate inhibitscis-diamminedichloroplatinum (II) activity. Cancer Chemother Pharmacol 13: 82–85

    Article  PubMed  CAS  Google Scholar 

  33. Vermorken JB, Kapteijn TS, Hart AAM, Pinedo HM (1983) Ototoxicity ofcis-diamminedichloroplatinum (II): influence of dose, schedule and mode of administration. Eur J Cancer Clin Oncol 19: 53–58

    Article  PubMed  CAS  Google Scholar 

  34. Vermorken JB, Vijgh WJF van der, Klein I, Gall HE, Groeningen CJ van, Hart GAM, Pinedo HM (1986) Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin. Clin Pharmacol Ther 39: 136–144

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Otolaryngology, Fukui Medical School, Matsuoka-cho, Yoshida-gun, 910-11, Fukui, Japan

    T. Saito, Z. J. Zhang, Y. Manabe, T. Ohtsubo & H. Saito

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  4. T. Ohtsubo
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Saito, T., Zhang, Z.J., Manabe, Y. et al. The effect of sodium thiosulfate on ototoxicity and pharmacokinetics after cisplatin treatment in guinea pigs. Eur Arch Otorhinolaryngol 254, 281–286 (1997). https://doi.org/10.1007/BF02905989

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  • DOI: https://doi.org/10.1007/BF02905989

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