Hyperhomocysteinemia is implicated in the pathogenesis of various liver diseases. In this study, the effects of S-adenosylmethionine (SAM) on hyperhomocysteinemia and steatosis with ethanol-induced liver injury in rats were examined and their mechanisms were explored.
Forty-eight female Sprague–Dawley rats were randomly divided into four groups as control, model, low-dose, and high-dose SAM groups. Except the control group, all rats were fed high-fat-containing diet plus ethanol and fish oil gavaged for 8 weeks. SAM was administered by intraperitoneal injection after the 4 weeks’ exposure of ethanol. Serum homocysteine (Hcy), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), tumor necrosis factor α (TNF-α), and transforming growth factor β1 (TGF-β1) levels were determined. The contents of liver malondialdehyde (MDA) and glutathione (GSH) were assayed. Liver histology was also examined. The expressions of TNF-α and TGF-β1 mRNAs in the liver were detected by the reverse transcriptase-polymerase chain reaction assay.
Compared with the control group, the model group rats developed marked liver damage, accompanied by an increase in Hcy, ALT, AST, TC, TG, TNF-α, TGF-β1, and MDA levels. However, the levels of GSH were decreased. These responses were associated with the increased expression of TNF-α and TGF-β1 mRNAs in the livers, as well as the existence of hepatocellular necrosis and neutrophil infiltration in the livers. In treatment groups, SAM provided significant protection from the liver injury induced by alcohol, resulting in a decrease in serum TNF-α, TGF-β1 levels, lipid peroxidation, and the expressions of TNF-α and TGF-β1 mRNAs in the livers, as well as an increase in GSH levels. However, no statistical difference was observed in these parameters between the two different dose treatment groups. In the study, SAM did not affect plasma total homocysteine (tHcy) levels significantly.
SAM prevents alcohol-induced liver injury in rats by reducing liver lipid peroxidation, anti-inflammation, and antihyperplasia. In addition, it does not affect the plasma tHcy levels.