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Food Chem Toxicol. 1995 Aug;33(8):641-51.

Protective effect of N-acetylcysteine against heterocyclic amine-induced cardiotoxicity in cultured myocytes and in rats.

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  • 1Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA.

Abstract

Cooked meat contains many mutagenic/carcinogenic heterocyclic amines (HAs), including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The reactive N-hydroxylamine metabolites N-hydroxy-IQ and N-hydroxy-PhIP are toxic to isolated rat cardiomyocytes. This study examined whether antioxidant agents protect against N-hydroxylamine-induced cardiotoxicity. In isolated rat cardiomyocytes, N-acetylcysteine, alpha-tocopherol and glutathione were protective against N-hydroxylamine-mediated lactate dehydrogenase release into the medium, suggesting that a free radical mechanism may be partly involved in HA-induced cardiotoxicity. Since N-acetylcysteine was by far the most protective of the agents investigated, the effects of N-acetylcysteine on HA-induced ultrastructural damage were further examined both in vitro and in vivo. Isolated cardiomyocytes treated with 1.2 mM N-acetylcysteine before and during exposure to N-hydroxy-IQ or N-hydroxy-PhIP showed a smaller percentage of ultrastructural abnormalities, such as myofilament loss, sarcoplasmic reticulum swelling and abnormal mitochondria. N-Acetylcysteine pretreatment also significantly reduced the percentage of cardiac cells with T-tubule dilation and myelin figures in adult rats dosed with IQ. The protective effect of N-acetylcysteine was not associated with a reduction in HA-DNA adducts, as assessed by 32P-postlabelling analysis of DNA from isolated cardiomyocytes treated with N-hydroxylamines. DNA adduct formation per se, therefore, may not be associated with the observed cardiotoxic effects of the HAs. Further studies are required to confirm the involvement of a free radical mechanism in HA cardiotoxicity.

PMID:
7672737
[PubMed - indexed for MEDLINE]
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