The aim of the current study was to determine the effects of α-lipoic acid (LA) on hyperuricemia and endothelial dysfunction, and to uncover the underlying mechanism of its action. A hyperuricemic rat model was established by administration of uric acid (UA) and the rats were orally fed with 2 g/kg/day LA or phosphate-buffered saline. Primary rat aortic endothelial cells were subsequently isolated, and a cell viability assay, apoptosis assay, enzyme nitric oxide synthase (eNOS) activity assay and mitochondrial function assay were all performed. For the in vitro study, human umbilical vein endothelial cells were used and western blotting was performed to assess Akt signaling activity. The results of the current study indicated that LA inhibited apoptosis, enhanced eNOS activity and production of nitric oxide (NO), and rescued mitochondrial mass and function in uric acid (UA)-treated endothelial cells. LA activated Akt signaling and inhibition of Akt signaling abolished the effects of LA on cell viability, NO production, ROS production and ATP levels in UA-treated endothelial cells. Therefore, the current study demonstrated that LA attenuated oxidant stress and inhibited apoptosis in UA-treated endothelial cells by activating Akt signaling. The results indicate that LA may serve as a therapeutic approach to treat hyperuricemia-induced endothelial dysfunction.
Keywords: Akt signaling; apoptosis; endothelial dysfunction; hyperuricemia; lipoic acid.