Protective Of L-theanine On Carbon Tetrachloride-induced Acute Liver Injury In Mice

We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl4)-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50,100or200mg/kg) once daily for seven consecutive days. On the seventh day, mice were treated with CCl4(10ml/kg of0.2%CCl4solution in olive oil) intraperitoneally two hours after the last administration of L-theanine, to induce acute liver injury in mice. At24h after CCl4treatment, mice were sacrificed, the blood and livers were obtained. Serum ALT and AST activities and bilirubin level were measured. The histopathological changes in the liver sections stained with H&E were examined. Hepatic CYP2E1was detected by western blotting. Liver MDA and GSH/GSSG levels and activities of antioxidant enzymes were measured. Serum TNF-a and IL-1(3levels were determined by ELISA. Hepatic COX-2and iNOS were detected by immunohistochemistry. Hepatic active caspase-3and cleaved PARP were detected by western blotting. Results:(1) L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level;(2) The morphological results showed that L-theanine attenuated liver histopathological changes induced by CCl4in mice;(3) L-theanine significantly prevented CCl4-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities;(4) L-theanine inhibited metabolic activation of CCl4through down-regulating cytochrome P4502E1(CYP2E1):(5) L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-α and IL-1βin sera, and expression of cyclooxygenase-2(COX-2) and inducible nitric oxide synthase (iNOS) in livers;(6) CCl4-induced activation of apoptotic related proteins including caspase-3and PARP in mouse livers was also prevented by L-theanine treatment. Conclusion: Our results suggest that L-theanine protects mice against CCl4-induced acute liver injury through inhibiting metabolic activation of CCl4and preventing CCl4-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis.