Abstract
Cisplatin treatment of rats results into a significant increase in the activity of Ca2+-independent nitric oxide synthase (NOS) in kidneys and liver. Significant enhancement of lipid peroxidation in gastric mucosa, kidneys and liver was also observed. The administration of N G-nitro-l-arginine methyl ester, an inhibitor of NOS, markedly reduced renal and gastrointestinal toxicity, and also decreased the content of blood urea nitrogen, serum creatinine, and incidence of diarrhoea along with a significant inhibition in lipid peroxidation in the target organs. The present report, while demonstrating the beneficial effect of the blockade of NO pathways during cisplatin chemotherapy, may be helpful in developing strategies for combating some of the toxic side-effects of the drug.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abrams MJ, Murrer BA. 1993 Metal compounds in therapy and diagnosis. Science 261, 725–730.
Athar M, Hasan SK, Srivastava RC. 1987 Evidence for the involvement of hydroxyl radical in nickel mediated enhancement of lipid peroxidation. Biochem Biophys Res Commun 147, 1276–1281.
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. 1990 Hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87, 1620–1624.
Fisher RA. 1954 Statistical Methods for Research Workers. London: Oliver and Boyd.
Fisher RL, Sanuik JT, Gandolfi AJ, et al. 1994 Toxicity of cisplatin and mercuric chloride in human kidney cortical slices. Hum Exp Toxicol 13, 517–523.
Francis NM, Allen JB, Mizel DE, et al 1993 Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178, 749–754.
Howell SB. 1991 Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. New York: Plenum.
Ignarro LJ. 1990 Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30, 535–560.
Kam PCA. Govender G. 1994 Nitric oxide: basic science and clinical application. Anaesthesia 49, 515–521.
Lepoivre M, Flaman JM, Henry Y. 1992 Early loss of the tyrosyl radical in ribonucleotide reductase of adenocarcinoma cells producing nitric oxide. J Biol Chem 267, 22994–23000.
Loehrer PJ, Einhorn LH. 1984 Cisplatin. Ann Intern Med 100, 704–713.
Mascolo N, Izzo AA, Barbato F, Capasso F. 1993 Inhibitors of nitric oxide synthetase prevent castor oil-induced diarrhoea in the rat. Br J Pharmacol 108, 861–864.
Middleton SJ, Shorthouse M, Hunter JO. 1993 Increased nitric-oxide synthesis in ulcerative colitis. Lancet 341, 465–466.
Naganuma A, Satoh M. Imura N. 1987 Prevention of lethal and renal toxicity of cis-diamminedichloroplatinum(II) by induction of metallothionein synthesis without compromising its antitumor activity in mice. Cancer Res 47, 983–987.
Pil PM, Lippard SJ. 1992 Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin. Science 256, 234–240.
Prestayko AW, Crooke ST, Carter SK. 1980 Cisplatin: Current Status and New Developments. New York: Academic Press.
Ravi R, Somani SM, Rybak LP. 1995 Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol 76, 386–394.
Salter M, Knowles RG, Moncada S. 1991 Widespread tissue distribution, species distribution and changes in the activity of Ca2+-dependent and Ca2+-independent nitric oxide synthases. FEBS Lett 291, 145–149.
Srivastava RC, Forelich J, Eichhorn GL. 1978 The effect of platinum binding on the structure of DNA and its function in RNA synthesis. Biochemie 6, 879–891.
Srivastava RC, Hasan SK, Jyotsana, Gupta S. 1993 Protective role of metallothionein in nickel induced oxidative damage. Biochem Mol Biol Int 30, 261–270.
Stuehr DJ. 1992 Mammalian nitric oxide synthases. Adv Enzymol 65, 287–345.
Trifiletti RR. 1992 Neuroprotective effects of N G-nitro-l-arginine in focal stroke in the 7-day old rat. Eur J Pharmacol 218, 197–198.
Vermeulen NP, Baldew GS, Los G, McVie JG, De Goeiji JJ. 1993 Reduction of cisplatin nephrotoxicity by sodium selinite. Lack of interaction at the pharmacokinetics level of both compounds. Drug Metab Dispos Biol Fate Chem 21, 30–36.
Von Hoff DD, Schilsky R, Reichert CM, et al. 1979 Toxic effects of cis-dichlorodiammineplatinum(II) in man. Cancer Treat Rep 63, 1527–1531.
Weinberg JB, Granger DL, Pisetsky DS, et al. 1994 The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous geomerulonephritis and arthritis by orally administered N G-monomethyl-l-argenine. J Exp Med 179, 651–660.
Wink DA, Kasprzak KS, Maragos CM, et al. 1991 DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254, 1001–1003.
Author information
Authors and Affiliations
Additional information
Present address: Department of Dermatology, Case Western Reserve University, Cleveland. OH 44106. USA.
Rights and permissions
About this article
Cite this article
Srivastava, R.C., Farookh, A., Ahmad, N. et al. Evidence for the involvement of nitric oxide in cisplatin-induced toxicity in rats. Biometals 9, 139–142 (1996). https://doi.org/10.1007/BF00144618
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00144618