Premium
Zinc accumulation in adriamycin‐induced cardiomyopathy in rats: Effects of melatonin, a cardioprotective antioxidant
Author(s) -
Morishima Itsuro,
Okumura Kenji,
Matsui Hideo,
Kaneko Shinji,
Numaguchi Yasushi,
Kawakami Kei,
Mokuno Shinji,
Hayakawa Makoto,
Toki Yukio,
Ito Takayuki,
Hayakawa Tetsuo
Publication year - 1999
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1999.tb00585.x
Subject(s) - melatonin , tbars , medicine , endocrinology , antioxidant , probucol , chemistry , lipid peroxidation , oxidative stress , cardiomyopathy , zinc , biochemistry , heart failure , organic chemistry
We have recently reported that melatonin protects against adriamycin‐induced cardiomyopathy whose pathogenesis may involve free radicals and lipid peroxidation. Melatonin has also been shown to affect zinc turnover. Since zinc may act as an antioxidant, we investigated the role of zinc in the pathogenesis of adriamycin‐induced cardiomyopathy as well as in the treatment of melatonin against this disorder. Sprague Dawley rats were given adriamycin (cumulative dose, 15 mg/kg); melatonin (cumulative dose, 84 mg/kg); adriamycin plus melatonin; adriamycin plus probucol, another antioxidant (cumulative dose, 90 mg/kg); or vehicle alone, according to previously‐used regimens. Cardioprotective effects of both antioxidants (melatonin and probucol) were confirmed by the parameters of fractional shortening, heart weight, heart/body weight ratio, ascites volume, and mortality. Adriamycin increased both the myocardial and plasma levels of thiobarbituric acid reactive substances (TBARS) and myocardial zinc levels, and decreased plasma zinc levels. The significant negative correlation observed between the myocardial and plasma zinc levels (r =0.73, P < 0.01) among the samples of adriamycin‐treated and control rats suggested an internal redistribution of zinc. Melatonin and probucol were equally effective in inhibiting the increase in myocardial TBARS as well as zinc levels, suggesting that myocardial zinc accumulation might be a protective response against adriamycin‐induced oxidative stress. Melatonin also inhibited the adriainycin‐induced decrease in plasma zinc levels; probucol was not as effective in doing so. In addition to melatonin's antioxidative effect, it may have the effect of maintaining the plasma zinc levels.