Lipoic Acid Favors Thiolsulfinate Formation After Hypochlorous Acid Scavenging: A Study with Lipoic Acid Derivatives

Abstract

Lipoic acid, the oxidized form of 6,8-dimercapto-octanoic acid has a strained cyclic disulfide in a 1,2-dithiolane ring. Recently its antioxidant activity gained attention. Hypochlorous acid (HOCl) is an oxidant produced by neutrophils. A prominent effect of HOCl is the inactivation of α-1-antiproteinase. Due to this inactivation, the ability of α-1-antiproteinase to inhibit elastase is lost. The resulting higher activity of elastase is held responsible for tissue damage in lung emphysema. We studied the HOCl scavenging capability of three metabolites of lipoic acid: tetranor-, bisnor-, and β-lipoic acid. To obtain some insight on the molecular basis of HOCl scavenging 1,2-dithiane-4,5-diol, cystine, lipoic acid methyl ester, and lipoamide were also included in the study. The extent of α-1-antiproteinase inactivation by HOCl in the presence of scavenger was taken as a parameter to quantify the scavenging activity. It was found that lipoic acid, tetranor- and bisnorlipoic acid, lipoic acid methyl ester, and lipoamide all showed the same activity toward HOCl. β-Lipoic acid, 1,2-dithiane-4,5-diol and cystine were less active. The products of lipoic acid after reaction with HOCl were studied using GC/MS. Indications for thiolsulfinate formation were found by comparing these products with the GC/MS profile of β-lipoic acid. Thiolsulfinate formation may also be suggested in the reaction of tetranor- and bisnorlipoic acid and lipoic acid methyl ester with HOCl. The present results show an antioxidant activity of the metabolites tetranor- and bisnorlipoic acid. The 1,2-dithiolane ring may enhance the reactivity toward HOCl compared to less strained disulfides, resulting in the formation a thiolsulfinate.