Antioxidant agent nimesulid and beta-blocker metoprolol do not exert protective effects against rat mitochondrial DNA alterations in adriamycin-induced cardiotoxicity

Biochem Biophys Res Commun. 1999 Jan 27;254(3):651-6. doi: 10.1006/bbrc.1998.0124.

Abstract

Possible protective effects of two therapeutical agents (nimesulid and metoprolol) in adriamycin-induced cardiotoxicity were examined in rat cardiomyocytes at the mitochondrial DNA (mt DNA) level. Analysis by PCR revealed the presence of multiple deletions in a large region of the long arc of mt DNA which codes for several important genes involved in oxidative phosphorylation, in all animals under drug administration. No differences were found in the frequency of defective mt DNA between the animals that received only adriamycin (83%, 10/12), nimesulid and adriamycin (92%, 13/14), or metoprolol and adriamycin (80, 12/15) (p = 0.004).

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • Base Sequence
  • DNA Damage
  • DNA, Mitochondrial / drug effects*
  • DNA, Mitochondrial / genetics
  • Doxorubicin / toxicity*
  • Heart / drug effects*
  • Male
  • Metoprolol / pharmacology*
  • Molecular Sequence Data
  • Point Mutation
  • Polymerase Chain Reaction
  • Rats
  • Rats, Wistar
  • Restriction Mapping
  • Sequence Deletion
  • Sulfonamides / pharmacology*

Substances

  • Adrenergic beta-Antagonists
  • Antioxidants
  • DNA, Mitochondrial
  • Sulfonamides
  • Doxorubicin
  • Metoprolol
  • nimesulide

Associated data

  • GENBANK/X14848