Oxidative stress in the aging rat heart is reversed by dietary supplementation with ( R )‐α‐lipoic acid

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Abstract
Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age‐related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as mea¬sured by the rates of 2,7‐dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not α‐tocopherol. A significant age‐related increase (P = 0.05) in steadystate levels of oxidative DNA damage was observed, as monitored by 8‐oxo‐2′‐deoxyguanosine levels. To inves¬tigate whether dietary supplementation with (R)‐α‐lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN‐93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA‐supplemented rats ex¬hibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial‐induced oxidative stress, which is signif¬icantly attenuated by lipoic acid supplementation.— Suh, J. H., Shigeno, E. T., Morrow, J. D., Cox, B., Rocha, A. E., Frei, B., Hagen, T. M. Oxidative stress in the aging rat heart is reversed by dietary supplementationwith (R)‐α‐lipoic acid. FASEB J. 15, 700‐706 (2001)
Funding Information
  • National Institute on Aging (RIAG17141A T.M.H.)
  • American Heart Association (9910089Z J.H.S.)
  • National Institutes of Health (DK48831, GM15431, GM42056, DK26657, and CA77839 J.D.M.)