Procyanidins Ameliorate Acetaminophen-induced Acute Liver Injury via Activating the Nrf-2/SOD-1 Signal Pathway

Abstract

Background and Objectives An overdose of acetaminophen (APAP) usually leads to acute liver injury, and oxidative stress is one of the fundamental mechanisms used to characterize it. Procyanidins (PCs) can reduce the oxidative stress in the liver of mice. This study aimed to investigate the potential protective role of PCs against APAP-induced acute liver injury. Materials and Methods Experiments were performed on male Kunming mice in six groups: phosphate-buffered saline, PCs, APAP, and PCs pretreated with 10, 50, and 100 mg/kg. The mice were peritoneally injected with PCs 30 min before the administration of APAP. First, survival rates of mice were scored every 12 hr for three days in succession. Furthermore, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T-Bil), total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) were determined. Additionally, histological analysis and hepatic oxidative stress including the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) were assessed. Finally, the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD-1 was detected by Western blotting. Results The data indicated that PCs improved survival rates of APAP-induced liver injury in mice models. Moreover, PCs could reduce the elevated serum levels of ALT, AST, T-Bil, TC, TG, TNF-α, IL-1β, and IL-6 due to APAP exposure with a dose-dependent manner. Besides, PCs pretreatment attenuated hepatic histopathological damage and oxidative stress which manifested the increases of SOD and GSH, whereas the decrease of MDA. Furthermore, PCs enhanced the protein expression of Nrf2 and SOD-1 in the PCs pretreatment groups compared with the APAP group. Conclusion PCs ameliorated APAP-induced acute liver injury, and Nrf2 signaling pathway modulating antioxidative stress might be involved in it.