Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats

In preceding papers, we proposed that procainamide hydrochloride, a class I antiarrhythmic agent, was able to protect mice and rats from cisplatin-induced nephrotoxicity and that it could exert its action through accumulation in kidneys followed by coordination with cisplatin (or its hydrolysis meta...

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Bibliographic Details
Published in:European journal of pharmacology 2002-05, Vol.442 (3), p.265-272
Main Authors: Zicca, Antonio, Cafaggi, Sergio, Mariggiò, Maria A, Vannozzi, Maria O, Ottone, Massimo, Bocchini, Vittorio, Caviglioli, Gabriele, Viale, Maurizio
Format: Article
Language:English
Subjects:
Animals
Anti-Arrhythmia Agents - pharmacology
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - toxicity
Biological and medical sciences
Cisplatin
Cisplatin - administration & dosage
Cisplatin - toxicity
Cytosol - metabolism
Drug Interactions
Drug toxicity and drugs side effects treatment
Feces - chemistry
Hepatotoxicity
Liver - drug effects
Liver - metabolism
Liver - pathology
Male
Medical sciences
Mitochondria, Liver - metabolism
Pharmacology. Drug treatments
Platinum - metabolism
Procainamide
Procainamide - pharmacology
Protection
Rats
Rats, Sprague-Dawley
Toxicity: digestive system
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Summary:In preceding papers, we proposed that procainamide hydrochloride, a class I antiarrhythmic agent, was able to protect mice and rats from cisplatin-induced nephrotoxicity and that it could exert its action through accumulation in kidneys followed by coordination with cisplatin (or its hydrolysis metabolites) and formation of a less toxic platinum compound similar to the new platinum(II) triamine complex cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate, obtained by the reaction of cisplatin with procaine hydrochloride. Hepatotoxicity is not considered as a dose-limiting toxicity for cisplatin, but liver toxicity can occur when the antineoplastic drug is administered at high doses. Here, we report that procainamide hydrochloride, at an i.p. dose of 100 mg/kg, reduces cisplatin-induced hepatotoxicity, as evidenced by the normalization of plasma activity of glutamic oxalacetic transaminase and γ-glutamyl transpeptidase, as well as by histological examination of the liver tissue. Twenty-four hours after i.p. treatment with the combination of 7.5 mg/kg cisplatin and 100 mg/kg procainamide, a significant increase of procainamide (+56%, P
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(02)01537-6