Reduction of cisplatin-induced nephrotoxicity by proteolytic enzymes in tumor-bearing rats

We investigated the polyenzyme drug, Wobe-Mugos E-(R), for its efficacy in reducing nephrotoxicity induced by antitumor chemotherapy with cisplatin. Investigations were performed in male Wistar rats with transplanted Guerin's carcinoma. One course of antitumor therapy with cisplatin consisted of five intraperitoneal injections (1.2 mg/kg) of the drug. Wobe-Mugos EO was administered either intramuscularly (eight injections, 10 mg/kg daily) or orally (11 intakes, 40 mg/kg daily). The nephroprotective effects of Wobe-Mugos E-(R) were confirmed by biochemical analysis of kidney function. Cisplatin administration in tumor-bearing rats resulted in an almost two-fold increase in blood serum creatinine and urea levels. Wobe-Mugos E-(R) in combination with cisplatin, irrespective of the route of administration, decreased blood serum creatinine and urea levels by 30%. In addition, kidney histology showed that coadministration of Wobe-Mugos EO significantly decreased cisplatin-induced nephrotoxicity. Only 28% of the rats receiving both cisplatin and Wobe-Mugos E-(R) showed signs of nephrotoxicity, while in 100% of the animals treated with cisplatin alone the compound showed cytotoxic effects on the renal parenchyma. Our data demonstrate that these polyenzyme drugs could be used to correct cisplatin-induced kidney damage. Proteolytic enzymes considerably reduce the nephrotoxicity caused by platinum-containing agents but do not reduce the antitumor effects of cisplatin.