Tea polyphenols inhibit expressions of iNOS and TNF-a and prevent lipopolysaccharide-induced liver injury in rats

<正>BACKGROUND: Tea polyphenols have been shown to protect against carbon tetrachloride ( CCl4) -induced liver injury, liver fibrosis, hepatic ischemia-reperfusion injury. In this study, we examined the effect of tea polyphenols on lipopolysaccharide ( LPS ) -induced liver injury, and explored its mechanisms. METHODS: Sprague-Dawley rats received tea polyphenols (100 mg · kg-1·d-1) or vehicle (water) intragastrically by gavage for 14 days, followed by LPS (5 mg/kg) or saline injection intraperitoneally. Liver injury was assessed by biochemical assay and pathological analysis. Serum tumor necrosis factor-α (TNF-α) levels and liver malondialdehyde (MOA) contents were determined. Inducible nitric oxide synthase (iNOS) protein and TNF-α, iNOS and en-dothelial nitric oxide synthase (eNOS) mRNA expressions in the liver were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: Administration of LPS resulted in liver injury in rats, evidenced by elevated activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatocellular necrosis, and neutrophil infiltration in the liver. These responses were associated with increased serum TNF-α levels, induced iNOS protein, expressions of TNF-α, iNOS mRNA in the liver and elevated lipid peroxidation at 90 minutes or 6 hours after LPS injection. Pretreatment with tea polyphenols attenuated LPS-induced liver injury, and blunted the rises of serum TNF-α levels and lipid peroxidation and the induction of expressions of TNF-α, iNOS in the liver. CONCLUSION: Tea polyphenols prevent LPS-induced liver injury, and the mechanisms may involve the reduction of serum TNF-α levels and lipid peroxidation and the suppression of TNF-α, iNOS expressions in the liver.