Summary
Although mesna afforded protection against the cytotoxicity of cisplatin in Chinese hamster cells, line V-79-753B, in vitro, there was no evidence for protection against nephrotoxicity when this drug combination was examined in the rat. It seems likely that cisplatin-induced nephrotoxicity is mediated by intracellular events in kidney cells which cannot be inhibited by mesna possibly due to its presence within cells in vivo as the stable and unreactive disulphide. On the basis of these data it is unlikely that combinations of mesna and cisplatin will be of therapeutic benefit in man.
This is a preview of subscription content, log in via an institution to check access.
Referneces
Borch RF, Pleasants ME (1979) Inhibition of cisplatinum nephroxicity by diethyldithiocarbamate rescue in a rat model. Proc Natl Acad Sci USA 76: 6611–6614
Brock N, Pohl J (1983) The development of mesna for regional detoxification. Cancer Treat Rev 10 [Suppl A]: 33–43
Brock N, Pohl J, Stekar J, Scheef W (1981) Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention: 2. Comparative study on the uroprotective efficiency of thiols and other sulfur compounds. Eur J Cancer Clin Oncol 17: 1155–1163
Brock N, Pohl J, Stekar J, Scheef W (1982) Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention: 3. Profile of action of sodium 2-mercaptoethane sulfonate (mesna). Eur J Cancer Clin Oncol 18: 1377–1387
Cooke BC, Fielden EM, Johnson M, Smithen CE (1976) Polyfunctional radiosensitizers: 1. Effect of a nitroxyl biradical on the survival of mammalian cells in vitro. Radiat Res 65: 152–162
Cox P (1979) Cyclophosphamide cystitis. Identification of acrolein as the causative agent. Biochem Pharmacol 28: 2045–2049
Crocker CL (1967) Rapid determination of urea nitrogen in serum or plasma without deproteinization. Am J Med Technol 33: 361
Einhorn LH, Donahue J (1977) cis-diammedichloro platinum, vinblastine and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 7: 293–298
Howell SB, Taetle R (1980) Effect of sodium thiosulfate on cis-dichlorodiammineplatinum (II) toxicity and antitumour activity in L1210 leukaemia. Cancer Treat Rep 64: 611–616
Howell SB, Pfeifle CE, Wung WE, Olshen RA (1983) Intraperitoneal cis-diamminedichloroplatinum with systemic thiosulfate protection. Cancer Res 43: 1426–1431
Ishizawa M, Taniguchi S, Baba T (1981) Protection by sodium thiosulfate and thiourea against lethal toxicity of cis-diamminedichloroplatinum (II) in bacteria and mice. Jpn J Pharmacol 31: 883–889
Link H, Neef V, Niethammer D, Willis K (1981) Prophylaxis of haemorrhagic cystitis due to cyclophosphamide-conditioning for bone-marrow transplantation. Blut 43: 329–330
Millar BC, Millar JL, Clutterbuck R, Jinks S (1983) Studies on the toxicity of cyclophosphamide in combination with mesna in vitro and in vivo. Cancer Treat. Rev [Suppl A] 10: 63–71
Ormstad K, Orrenius S, Lastbom T, Uehara N, Pohl J, Stekar J, Brock N (1983) Pharmacokinetics and metabolism of sodium 2-mercaptoethanesulfonate in the rat. Cancer Res 43: 333–338
Scheulen ME, Niederle N, Bremer K, Schutte J, Seeber S (1983) Efficacy of ifosphamide in refractory malignant disease and uroprotection by mesna: results of a clinical phase II — study with 151 patients. Cancer Treat Rev [Suppl A] 10: 93–101
wiltshaw E, Kroner T (1976) Phase II study of cis-dichlorodiammine platinum (II) in advanced adenocarcinoma of the ovary. Cancer Treat Rep 60: 55–60
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Millar, B.C., Siddik, Z.H., Millar, J.L. et al. Mesna does not reduce cisplatin induced nephrotoxicity in the rat. Cancer Chemother. Pharmacol. 15, 307–309 (1985). https://doi.org/10.1007/BF00263907
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00263907