1. ¹Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan
2. ²Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan
3. ³Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan

Correspondence: M Nishikawa, Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. E-mail: makiya@pharm.kyoto-u.ac.jp

Received 8 November 2006; Accepted 5 December 2006; Published online 26 September 2007.

Abstract

Cisplatin is frequently used to treat solid tumors; however, nephrotoxicity due to its reactive oxygen species-mediated effect limits its use. We tested the ability of cationized catalase, a catalase derivative, to inhibit nephrotoxicity in cisplatin-treated mice. Immunohistochemical analysis showed that the catalase derivative concentrated in the kidney more efficiently than native catalase. Repeated intravenous doses of cationized catalase significantly decreased cisplatin-induced changes in serum creatinine, blood urea nitrogen, nitrite/nitrate levels, lactic dehydrogenase activity, and renal total glutathione and malondialdehyde contents. In addition, cationized catalase effectively blunted cisplatin-induced proximal tubule necrosis but had no significant effect on the cisplatin-induced inhibition of subcutaneous tumor growth. Repeated doses of catalase, especially cationized catalase, significantly increased the survival of cisplatin-treated tumor-bearing mice preventing cisplatin-induced acute death. Our studies suggest that catalase and its derivatives inhibit cisplatin-induced nephrotoxicity, thus improving the efficiency of cisplatin to treat solid tumors.