Effect of the antiarrhythmic drug procainamide on the toxicity and antitumor activity of cis-diamminedichloroplatinum(II)

Mauro Esposito, Maurizio Viale, Maria Ornella Vannozzi, Antonio Zicca, Angela Cadoni, Franco Merlo, Luca Gogioso

Research output: Contribution to journalArticlepeer-review

Abstract

The class I antiarrhythmic drug procainamide (Pd) was tested on BDF1 mice for its chemoprotective activity against cis-diamminedichloroplatinum(II) (DDP) toxicity. Pd at the dose of 50 mg/kg protected mice against otherwise lethal doses of DDP (survivors at Day 14 after 25 mg/kg DDP or 25 mg/kg DDP-Pd treatment: 0% vs 100%) and greatly reduced the weight loss induced by DDP. Moreover, the increased plasma urea nitrogen levels caused by a single ip administration of DDP in water (8 or 16 mg/kg) as well as the tubular degenerative changes detected by light microscopy were prevented by Pd. Pd had no effect on the sensitivity of P388 leukemic cells to DDP in vitro, but the administration of DDP (16 mg/kg) and Pd (50 mg/kg) to BDF1 mice bearing P388 leukemic cells produced a significant increase in survivals compared to mice receiving ip DDP alone diluted in 0.9% NaCl solution. The increased efficacy of this combination therapy in P388 leukemic mice compared to a single DDP treatment at the same dose was observed both when the drugs were administered ip simultaneously (p = 0.042) and when DDP and Pd were given ip and iv, respectively (p = 0.018). Since procaine, which differs from Pd merely in the replacement of the amide by the ester linkage, has also been reported to significantly enhance DDP efficacy (M. Esposito et al., 1990, J. Natl. Cancer Inst. 82, 677-684), a comparison of their effects in tumored mice exposed to DDP has been made. Although both drug combinations were superior to that of DDP alone, in terms of both survival time and numbers of cures, Pd treatment seems to offer better protection against DDP-induced lethality than did procaine.

Original languageEnglish
Pages (from-to)370-377
Number of pages8
JournalToxicology and Applied Pharmacology
Volume140
Issue number2
DOIs
Publication statusPublished - Oct 1996

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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