Abstract: Lipoic acid (LA) and resveratrol (RES) are two important natural antioxidant agents. Acetaminophen (APAP) is a common analgesic drug. However, excess administration of APAP may cause oxidative stress and liver damage. In this paper, an in vitro cell model was used to compare the antioxidant effects of RES and LA on APAP-induced oxidative damage in HepG2 cells, and to explore the underlying mechanisms. The aim of this study was to provide a technical basis for the prevention and treatment of liver damage caused by acetaminophen. The effects of different concentrations of LA and RES on APAP-induced apoptosis in HepG2 cells were detected by Cell Counting Kit-8 (CCK-8) method. The antioxidant activities of LA and RES were comparatively evaluated using cellular antioxidant activity (CAA) method. Flow cytometry was used to detect apoptosis. The content of malondialdehyde (MDA) and the activity of glutathione (GSH) and superoxide dismutase (SOD) were detected by enzyme labeling method. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were used to detect the expression of the apoptosis-related genes Bax, Bcl-2 and caspase-3. Cytotoxicity test results showed that both resveratrol and lipoic acid could increase the viability of cells, and LA was more effective than RES. CAA results showed that LA inhibited dichlorofluorescein (DCF) production more strongly than did RES. The results of flow cytometry showed that both LA and RES could inhibit apoptosis induced by oxidative stress, and the effect of LA was stronger than that of RES. The results of enzyme labeling, qPCR and Western blot showed that LA and RES inhibited APAP-induced apoptosis by decreasing MDA content, increasing GSH and SOD activity, up-regulating Bcl-2 expression, and down-regulating Bax and caspase-3 expression, with LA being more effective than RES. To sum up, compared with RES, LA had a more protective effect on APAP-induced liver injury, and the underlying mechanism may be related to reducing oxidative stress and inhibiting apoptosis.

Key words: lipoic acid, resveratrol, acetaminophen, HepG2 cells, cell damage