Protective mechanism of tanshinone on acute liver failure induced by D-galactosamine in rats

Objective To investigate the protective effect and mechanism of tanshinone ⅡA on D-galactosamine (D-GalN)-induced acute liver failure in rats.

Methods SD rats were randomly divided into control group, model group (intraperitoneal injection of 1.1 g/kg D-GalN), low-dose group (intraperitoneal injection of 1.1 g/kg D-GalN + daily gavage of 25 mg/kg tanshinone ⅡA), and High-dose group (intraperitoneal injection of 1.1 g/kg D-GalN + daily gavage of 50 mg/kg tanshinone ⅡA). Liver function indicatorsaspartate aminotransferase(AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (γ-GT)were measured using a Hitachi7600-210 biochemical analyzer, and serum total bilirubin (TBIL) and direct bilirubin (DBIL) levels were determined. The mitotic index (MI) and proliferating cell nuclear antigen (PCNA) positivity in liver tissues were examined. Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma levels of tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-10, and IL-6 in rats from each group. Kits were employed to measure superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) contents in liver tissues of rats from each group. The TUNEL method was adopted to detect hepatocyte apoptosis rates in liver tissues, and immunoblotting was used to assess the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2) proteins in liver tissues.

Results Compared with the control group, the model group exhibited increased p-ERK1/2 protein expression (P < 0.05). Compared with the model group, both the low-dose and high-dose groups showed decreased p-ERK1/2 protein expression (P < 0.05). The model group had an increased hepatocyte apoptosis index compared with the control group (P < 0.05). Both the low-dose and high-dose groups demonstrated decreased hepatocyte apoptosis indices compared with the model group(P < 0.05). Compared with the control group, the model group had increased MDA levels and decreased SOD and GSH levels (P < 0.05). Both the low-dose and high-dose groups exhibited decreased MDA levels and increased SOD and GSH levels compared with the model group (P < 0.05). The model group showed increased levels of TNF-α, IL-1β, IL-10, and IL-6 compared with the control group (P < 0.05). Both the low-dose and high-dose groups had decreased levels of TNF-α, IL-1β, IL-10, and IL-6 compared with the model group (P < 0.05). Compared with the control group, the model group had decreased MI and PCNA positivity rates (P < 0.05). Both the low-dose and high-dose groups exhibited increased MI and PCNA positivity rates compared with the model group (P < 0.05). The model group had increased AST, ALT, γ-GT, TBIL and DBIL values compared with the control group (P < 0.05). Both the low-dose and high-dose groups showed decreased AST, ALT, γ-GT, TBIL and DBIL values compared with the model group (P < 0.05).

Conclusion Tanshinone ⅡA may alleviate D-GalN-induced acute liver failure in rats through the ERK1/2 signaling pathway.