Protective Effect of Procaine Against Cisplatin Induced Nephrotoxicity in Mice

Abstract

Clinical data suggest a dose response curve for cisplatin (DDP) in a number of human neoplasm. In an attempt to increase the therapeutic index of this drug, a host of compounds that reduce DDP nephrotoxicity allowing the administration of higher doses of the drug is under study; concern however exists that reduction of toxicity may also reduce the antitumor activity of DDP. Procaine is a local anesthetic drug that modifies several membrane-mediated cellular processes and in experimental tumor systems has been shown to potentiate antineoplastic agents in vitro. In addition, based upon our previous observations that a) procaine protects V79 hamster cells from the mutagenic effects of DDP without decreasing the cytotoxicity of this drug in vitro and b) procaine does not alter the sensitivity of human colon carcinoma cells, HCT-8 to DDP in vitro, we have tested the lethality and efficacy of DDP, procaine and their combinations in vivo.