Morphological and histochemical evidence of the protective effect of procainamide hydrochloride on tissue damage induced by repeated administration of low doses of cisplatin.

Background: The class I antiarrhythmic drug procainamide hydrochloride might protect against acute cisplatin-induced nephrotoxicity and hepatotoxicity in mice and rats. In this report, the protective activity of procainamide hydrochloride against renal and hepatic tissue damage induced by repeated administration of low doses of cisplatin was analyzed morphologically and histochemically. Materials and Methods: Light microscopy observations were performed on liver, renal and heart samples obtained from female Wistar rats treated twice a week for 10 weeks with 1 mg/kg cisplatin (cumulative dose: 20 mg/kg), with or without 100 mg/kg procainamide hydrochloride (cumulative dose: 2 g). Samples were then submitted to histochemical stainings (i.e. H & E, periodic acid Schiff (PAS) and Sudan Black). Results: Light microscopy analysis revealed that the coadministration of cisplatin and procainamide hydrochloride significantly reduced tissue alterations both in the kidneys and liver, while in the heart, neither cisplatin nor the combination of cisplatin and procainamide hydrochloride caused any evident tissue damage. Conclusion: The morphological and histochemical data confirm that procainamide hydrochloride is able to protect not only from acute cisplatin-induced toxicities, but also from tissue alterations induced in the liver and kidneys by the administration of repeated low doses of cisplatin. In our previous work, we demonstrated that procainamide hydrochloride, a class I antiarrythmic drug, was able to reduce some of the acute toxic effects of cisplatin, in particular the dose-limiting nephrotoxicity and the mild and transient hepatotoxicity (1-3). In general, the risk of these and