Alpha-Lipoic Acid Protects against Hepatic Ischemia-Reperfusion Injury in Rats

Abstract

Background and Aim: To evaluate the protective effect of alpha-lipoic acid in reducing oxidative damage after severe hepatic ischemia/reperfusion (IR) injury. Methods: Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by 60 min reperfusion period. Lipoic acid (100 mg/kg i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and cytokine, TNF-α and IL-1β levels were determined in serum samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Results: Serum ALT, AST, and LDH activities and TNF-α and IL-1β levels were elevated in the I/R group, while this increase was significantly lower in the group of animals treated concomitantly with lipoic acid. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in lipoic acid-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels and MPO activity due to I/R injury were reduced back to control levels with lipoic acid treatment. Conclusion: Since lipoic acid administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that lipoic acid with its antioxidant and oxidant-scavenging properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.

α-Lipoic acid and ebselen prevent ischemia/reperfusion injury in the rat intestine

“…40 Its ability to mimic GPx is the most likely explanation for increased SOD and GPx activity. 11,17 Although experimental studies on I/R injury suggest that α-LA and ebselen may prevent or reduce cell and tissue damage of the liver, kidneys, brain, bladder, and myocardium, 17,35,36,[41][42][43][44] their effect on intestinal tissue subjected to I/R has not been evaluated, to our knowledge. Our fi ndings suggest that their combination may protect intestinal tissue against I/R injury, based on an antioxidant effect.…”

Antioxidative effects of α-lipoic acid in the brain, liver and kidneys in selected mouse organs exposed to zymosan

“…It should be emphasized that several other studies have also provided evidence for protective effects of ALA supplementation against oxidative tissue damage in various animal models of ischemia -reperfusion, hepatic disorders, and diabetes [6,12]. According to Feng et al [14] α-lipoic acid has effects on the kidneys of diabetic rats, increasing the levels of GSH, SOD, vitamins E, and C in ALA-treated group, compared to the diabetic group.…”

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

“…Adenovirus-mediated gene delivery of the cytosolic Cu/Zn superoxide dismutase gene in a rat marginal liver transplant model reduced OFR production and reduced liver injury (36). The use of manganese-porphyrin (MnP) complexes with superoxide dismutase (SOD) reduced liver IRI in murine models (37), as did administration of α-lipoic acid with OFR-scavenging properties (38). Delivery of newer antioxidant agents has similarly mitigated liver IRI through scavenger effects (39)(40)(41)(42)(43).…”