The influence of lipoic acid on caveolin-1-regulated antioxidative enzymes in the mouse model of acute ulcerative colitis.

Abstract

This study was undertaken to verify if two-weeks treatment of lipoic acid (LA) influence colon damage and pro-inflammatory cytokine synthesis during DSS-induced acute colitis. Moreover, as LA has anti-oxidative properties, we analyzed its influence on the level of antioxidative enzymes, HO-1 and eNOS, and their regulator- caveolin-1. LA was administrated to male C57/BALBc mice at a dose of 25 or 50mg/kg/day (i.p.) for 21days. Acute colitis was induced by administration of 4% DSS (w/v) in drinking water for 5days, followed by 2days of normal drinking water. Mice in LA+DSS groups were treated with LA (25 or 50mg/kg/day; i.p.) starting 14days prior to 4% DSS. Control group received saline for 21days. In the colon tissue we measured myeloperoxidase activity (MPO), IL-1β, IL-6, IL-17A, IL-23 (ELISA method), and tissue level of cav-1, phospho-eNOS, total eNOS and HO-1 (Western blot). Administration of DSS significantly increased total colon damage (p<0.001), myeloperoxidase (MPO) activity (p<0.05) and pro-inflammatory IL-6 (p<0.05). There was also a tendency towards higher IL-1β, IL-17A, and IL-23 in the colon. LA alone did not influence total colon damage, MPO activity, and pro-inflammatory cytokines concentration compared to control (p<0.05). Notably, mice treated with LA and DSS had significantly decreased total colon damage score (p<0.001), despite augmented colon MPO activity (p<0.01), but similar (IL-17A) or even significantly higher level (IL-1β, IL-23) as compared to the DSS group (p<0.05). IL-6 was insignificantly decreased after LA treatment at a dose of 50mg/kg. In acute colitis there was a tendency towards an increase in cav-1 and HO-1 and a decrease p-eNOS/total eNOS ratio. Moreover, the LA+DSS groups had higher expression of HO-1 and p-eNOS/total eNOS (p<0.05) compared to the DSS group, and a tendency towards higher cav-1 level. The changes did not depend on LA dose. Our study indicated that LA, at lower doses, may influence cav-1-regulated antioxidative enzyme levels (HO-1 and p-eNOS/total eNOS) despite an increase in colon pro-inflammatory cytokine levels during acute colitis. Hence, LA treatment may be - to some extent - beneficial in attenuation of acute colitis.