Improvement of Cisplatin Toxicity and Lethality by Juzen-taiho-to in Mice

Abstract

The effects of oral treatment with 1-, 5-, 10- and 20-fold the usual daily dose of Juzen-taiho-to on the nephrotoxicity, immunosuppression, hepatic toxicity and gastrointestinal toxicity caused by i. p. administration of 3.0 mg/kg cisplatin (CDDP) 9 times (on days 3, 4, 5, 6, 7, 8, 10, 11, and 12) were examined in ddY mice inoculated with sarcoma 180 (S-180) cells on day 1. The increase in blood urea nitrogen, serum creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminases and relative stomach weight and decrease in white blood cell count, platelet count, relative spleen and thymus weight, food intake and body weight caused by CDDP were inhibited to nearly the control levels without reducing the antitumor activity of CDDP against S-180 by the oral treatment with either 10-fold (1.7 g/kg) or 20-fold (3.4 g/kg) the usual daily dose of Juzen-taiho-to 12 times (on days 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, and 15). All the mice receiving 4.5, 6.0, 7.5, 9.0, and 12.0 mg/kg CDDP died by day 12, while treatment with 3.4 g/kg Juzen-taiho-to efficiently prolonged the survival time. These findings indicate that Juzen-taiho-to may provide protection against most clinical toxicity caused by CDDP, and Juzen-taiho-to may allow us to administer a much higher dose of CDDP in clinical therapy.