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Antioxidant properties of thioctic and dihydrolipoic acid have been demonstrated in membranes and low density lipoproteins (LDL) in vitro. In vivo studies with dietary supplementation of thioctic acid to rats showed that it can also protect tissues against oxidative damage. Presumably, this action is due to a thioctic acid dihydrolipoic acid (TA/DHLA) coupled antioxidant mechanism, which enhances the activity of other antioxidants (i.e. ascorbate, α-tocopherol) by regenerating them from their radical form.In the present study, thioctic acid proved to protect against ischemia/reperfusion injury to Langendorff perfused hearts. Hearts isolated from rats fed thioctic acid and subjected to ischemia exhibited better mechanical recovery (left ventricular developed pressure) after reperfusion and lower lactate dehydrogenase leakage. Thioctic acid supplementation also decreased the appearance of fluorescent lipid peroxidation products after ischemia/reperfusion, lowered the rate of 2,2'-azobis-(2,4-dimethylvaleronitrile) (AMVN) induced lipid peroxidation in heart homogenates, and prevented the loss of α-tocopherol. The total sulfhydryl group content in thioctic acid fed animals was higher and the decrease due to ischemia-reperfusion was not as marked in this group as observed in the control. These results show that dietary supplementation with thioctic acid in vivo provides protection against ischemia/reperfusion injury in the Langendorff heart model.