Abstract: Objective: To explore the protective mechanism of grape seed proanthocyanidin extract (GSPE) against oxidative damage induced by arsenic for the purpose of providing a theoretical foundation for the prevention and treatment of arsenic poisoning and for the evaluation of the antioxidant activity of GSPE. Methods: HL-7702 cells were randomly divided into seven groups: control, arsenic poisoning (25 μmol/L), GSPE intervention (5, 10, 25 and 50 mg/L), and single GSPE treatment (50 mg/L) groups. After treatment for 24 and 48 h, the levels of aspartate transaminase (AST), alanine aminotransferase (ALT), glutathione (GSH), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) were determined by commercial kits. Cell viability was tested by 3-(4,5)-dimethylthiahiazo(-z-yl)- 3,5-di-phenytetrazoliumromide (MTT). We used polymerase chain reaction (PCR) and Western blot to detect the mRNA and protein expression levels of nuclear factor erythroid-2 related factor 2 (Nrf2), glutathione S-transferase (GST), heme oxygenase 1 (HO-1), and quinone oxidoreductase 1 (NQO1). Results: The cell viability in the high-concentration arsenic groups (≥ 25 μmol/L) was significantly lower than that in the control group (P < 0.05). The levels of ALT, AST and MDA in the GSPE intervention group were significantly lower than those in the arsenic poisoning group (P < 0.05), while a significant elevation was observed for GSH, T-AOC and SOD (P < 0.05). The mRNA and protein expression levels of Nrf2, GST, HO-1 and NQO1 in the GSPE intervention group were significantly elevated when compared with the arsenic poisoning group (P < 0.05). Conclusion: GSPE has an antagonistic action against arsenic poisoning in a dose-dependent manner by activating the Nrf2-mediated signaling pathway to improve the antioxidant capacity of cells and consequently reduce arsenic-induced liver oxidative injury.

Key words: grape seed proanthocyanidin extract, arsenic, antioxidant activity, nuclear factor erythroid-2 related factor 2 (Nrf2)