Abstract
Owing to an outstanding wide antitumor spectrum and excellent anti-tumor effect cisplatin has been used in chemotherapy for malignant tumor. However, cisplatin has strong side effects such as renal injury. Taurine has been found to protect against inflammatory tissue damage in a variety of experimental models. The aim of the present study was to investigate the effect of taurine against iNOS dependent DNA damage in cisplatin-induced renal injury in rats. With the help of a rat model of drug-induced kidney damage, we have assessed the nephrotoxic effects of different doses of cisplatin in the presence and absence of taurine. Immunohistochemical methods were used to examine the distribution of arginine, iNOS, citrulline and 8-nitroguanine in renal tissue. The expression levels of citrulline, iNOS, and 8-nitroguanine immunoreactivities were found to increase as a function of the dose of cisplatin used, and to decrease in the presence of taurine. The expression level of arginine immunoreactivity was reduced as a function of the dose of cisplatin used. On the other hand, iNOS, 8-nitroguanine and citrulline immunohistochemical staining showed an intense immunoreactivity in the renal tubule of cisplatin-treated animals; and arginine immunoreactivity was localized in the renal tubule of taurine-treated animals. We also confirmed the decrease of citrulline and iNOS expression in the renal tubule after taurine administration as well as the expression level of 8-nitroguanine, a nitrative stress marker in the same animals. The present results support the concept that taurine may have a protective role in the formation of cisplatin-related DNA lesions arising through iNOS-mediated nitrative stress.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Barabas K, Milner R, Lurie D, Adin C (2008) Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol 6:1–18
Chirino YI, Pedraza-Chaverri J (2009) Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol 61:223–242
Dasari S, Tchounwou PB (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364–378
Domitrovic R, Cvijanovic O, Pugel EP, Zagorac GB, Mahmutefendic H, Skoda M (2013) Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney. Toxicology 310:115–123
dos Santos NA, Carvalho Rodrigues MA, Martins NM, dos Santos AC (2012) Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update. Arch Toxicol 86:1233–1250
Gordon RE, Heller RF (1992) Taurine protection of lungs in hamster models of oxidant injury: a morphologic time study of paraquat and bleomycin treatment. Adv Exp Med Biol 315:319–328
Han X, Budreau AM, Chesney RW (2000) The taurine transporter gene and its role in renal development. Amino Acids 19:499–507
Hanigan MH, Devarajan P (2003) Cisplatin nephrotoxicity: molecular mechanisms. Cancer Ther 1:47–61
Jacobsen JG, Smith LH (1968) Biochemistry and physiology of taurine and taurine derivatives. Physiol Rev 48:424–511
Kato T, Okita S, Wang S, Tsunekawa M, Ma N (2015) The effects of taurine administration against inflammation in heavily exercised skeletal muscle of rats. Adv Exp Med Biol 803:773–784
Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7:573–584
Kintzel PE (2001) Anticancer drug-induced kidney disorders. Drug Saf 24:19–38
Kroning R, Lichtenstein AK, Nagami GT (2000) Sulfur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines. Cancer Chemother Pharmacol 45:43–49
Ma N, Aoki E, Semba R (1994) An immunohistochemical study of aspartate, glutamate, and taurine in rat kidney. J Histochem Cytochem 42:621–626
McWhinney SR, Goldberg RM, McLeod HL (2009) Platinum neurotoxicity pharmacogenetics. Mol Cancer Ther 8:10–16
Mozaffari MS, Schaffer SW (2002) Chronic taurine treatment ameliorates reduction in saline-induced diuresis and natriuresis. Kidney Int 61:1750–1759
Mozaffari MS, Miyata N, Schaffer SW (2003) Effects of taurine and enalapril on kidney function of the hypertensive glucose-intolerant rat. Am J Hypertens 16:673–680
Pabla N, Dong Z (2008) Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 73:994–1007
Pasantes-Morales H, Cruz C (1985) Taurine: a physiological stabilizer of photoreceptor membranes. Prog Clin Biol Res 179:371–381
Perazella MA, Moeckel GW (2010) Nephrotoxicity from chemotherapeutic agents: clinical manifestations, pathobiology, and prevention/therapy. Semin Nephrol 30:570–581
Ries F, Klastersky J (1986) Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. Am J Kidney Dis 8:368–379
Rybak LP (2007) Mechanisms of cisplatin ototoxicity and progress in otoprotection. Curr Opin Otolaryngol Head Neck Surg 15:364–369
Sato S, Yamate J, Saito T, Hosokawa T, Saito S, Kurasaki M (2002) Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin. Naunyn Schmiedeberg’s Arch Pharmacol 365:277–283
Sugiura H, Okita S, Kato T, Naka T, Kawanishi S, Ohnishi S, Oshida Y, Ma N (2013) Protection by taurine against INOS-dependent DNA damage in heavily exercised skeletal muscle by inhibition of the NF-kappaB signaling pathway. Adv Exp Med Biol 775:237–246
Thurston JH, Hauhart RE, Dirgo JA (1980) Taurine: a role in osmotic regulation of mammalian brain and possible clinical significance. Life Sci 26:1561–1568
Acknowledgements
This work was partly supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media B.V.
About this paper
Cite this paper
Kato, T., Tsunekawa, M., Wang, S., Yamashita, T., Ma, N. (2017). Effect of Taurine on iNOS-Mediated DNA Damage in Drug-Induced Renal Injury. In: Lee, DH., Schaffer, S.W., Park, E., Kim, H.W. (eds) Taurine 10. Advances in Experimental Medicine and Biology, vol 975. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1079-2_56
Download citation
DOI: https://doi.org/10.1007/978-94-024-1079-2_56
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-024-1077-8
Online ISBN: 978-94-024-1079-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)