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-lipoic acid
1
* Linus Pauling Institute and
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA; and
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
1Correspondence: Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331, USA. E-mail: tory.hagen{at}orst.edu
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 measured 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
-tocopherol. A significant age-related increase (P =
0.05) in steady-state levels of oxidative DNA damage was observed, as
monitored by 8-oxo-2'-deoxyguanosine levels. To investigate whether
dietary supplementation with (R)--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 exhibited 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 significantly 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 supplementation with
(R)--lipoic acid.
Key Words: aging • cardiac myocytes • oxidative stress • lipoic acid
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