Zinc accumulation in adriamycin‐induced cardiomyopathy in rats: Effects of melatonin, a cardioprotective antioxidant

Abstract

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 adriamycin-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.

Pharmacology and Physiology of Melatonin in the Reduction of Oxidative Stress in vivo

“…On the basis of this, it would be predicted that melatonin would be more effective in protecting lipidrich cellular membranes from oxidative damage than it would cytosolic protein or nuclear DNA. While there is no doubt that in vivo melatonin significantly reduces lipid peroxidation in membranes induced by a wide variety of agents [38][39][40][41], it is also highly effective (and possibly more so) in reducing free radical damage to DNA [42][43][44][45][46]. This is consistent with the reported high concentrations of melatonin in the nuclei of cells [23,24].…”

The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia–reperfusion injury in rabbits: experimental study

“…It was reported that zinc decreased oxidative stress by having an effect as an antioxidant. 15 Parallel to these, it was suggested that melatonin supplementation causes the antioxidant characteristic to emerge by increasing plasma zinc levels 32 and at the same time by increasing Cu-Zn-SOD activity. 33 When the part of the study related to NO was evaluated, I/R procedure did not result with significant difference in NO levels.…”

Actions of Melatonin in the Reduction of Oxidative Stress

“…The efficiency of any agent that destroys macromolecules by processes involving free radicals should be decreased if antioxidants, including melatonin, are also present. This has been shown to be the case with melatonin; it has been effectively utilized in vitro and in vivo to combat an incredibly wide number of toxicants including peroxynitrite [22][23][24]65], indomethacin [3], alloxan [26], cisplatin [51], glutamate [29], carbon tetrachloride [62], adriamycin [60], hydrogen peroxide [96], amyloid ß protein [72,73], carrageenan [22][23][24], cerulein [83], nitrilotriacetate [82] and many others [35,87,93,99]. Melatonin has proven equally effective in reducing oxidative damage in conditions where free radical involvement has been established; such situations include ischemia/reperfusion injury [22,111], biliary obstruction [59], ionizing radiation [110], etc.…”