Cigarette smoke induced oxidation of human plasma proteins, lipids, and antioxidants; selective protection by the biothiols dihydrolipoic acid and glutathione.

Exposure of human plasma to gas-phase cigarette smoke (CS) causes loss of human plasma antioxidants, protein modification (Frei et al, Biochem J, 1991 277:133-138; Reznick et al, Biochem J, 1992 286: 607-611) and a minimal amount of lipid oxidation. Ascorbic acid was found to prevent CS-induced lipid peroxidation and glutathione (GSH) partially protected against protein modification, as determined by loss of protein -SH groups and by increases in carbonyl content as a measure of protein oxidation. In the present study we demonstrate that dihydrolipoic acid (0.25-1.0 mM) decreases CS-induced protein carbonyls, α-tocopherol loss, and lipid hydroperoxide formation in plasma. In contrast GSH (1 mM) failed to influence CS-induced loss of α-tocopherol, and was 50% as effective as dihydrolipoate in protecting against CS-induced protein carbonyl formation. On the other hand, lipoic acid (oxidized form of dihydrolipoic acid) and oxidized glutathione (GSSG) had minimal effect in protecting against the CS-induced protein modifications. These findings demonstrate that low molecular weight thiols are capable of modifying the effect of gas-phase CS on biological fluids. Dihydrolipoate appears to be particularly useful in that it was shown to conserve ascorbic acid and α-tocopherol, i.e. supporting the antioxidant network concept in protection against protein and lipid oxidation.