Specific Reduction of Toxic Side Effects of Adriamycin by Induction of Metallothionein in Mice

Akira Naganuma, Masahiko Satoh, Nobumasa Imura

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77 Citations (Scopus)

Abstract

The effect of preinduction of metallothionein (MT) by bismuth (Bi) compounds on the toxic side effects and antitumor activity of adriamycin (ADR) was investigated in mice. Preinduction of MT by oral administration of bismuth subnitrate (BSN) significantly decreased the lethal toxicity, cardiotoxicity and bone marrow toxicity observed with a single subcutaneous injection of ADR. A significant increase in the concentration of cardiac MT was observed in mice treated with BSN. The MT level in the heart was significantly correlated with the protective effect of BSN against the cardiotoxicity of ADR. In tumor‐bearing mice, pretreatment with BSN did not affect the antitumor activity of ADR, although its cardiotoxicity was significantly depressed. The ability of BSN to reduce specifically the toxicity of ADR may be ascribed to the fact that Bi induces MT in the target tissue of ADR toxicity but not in a tumor. The protective effect of MT against the toxicity of ADR, which is believed to act as an anticancer agent by generating active oxygen, can be assumed to be due to its ability to scavenge free radicals or inhibit their formation.

Original languageEnglish
Pages (from-to)406-411
Number of pages6
JournalJapanese Journal of Cancer Research
Volume79
Issue number3
DOIs
Publication statusPublished - 1988 Mar

Keywords

  • Adriamycin
  • Bismuth
  • Cardiotoxicity
  • Metallothionein
  • Peroxidation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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