Theaflavins Relieve Fatty Liver Ischemia-reperfusion Injury Of Mice

Background and Aim:Nowadays liver donor shortage and the incidence of non-alcoholic fatty liver disease (NAFLD) are increasing and this has required the acceptance of steatotic livers for transplantation. However, steatotic livers were known to increase more severe acute ischemia-reperfusion (I/R) injury. Theaflavin (TF), a polyphenol substance extracted from black tea, has been reported to have anti-obesity, hypolipidemic, and anti-oxidant effects. In this study we tried to examine whether and how theaflavin can attenuate acute I/R injury in fatty liver.Methods:For in vivo study, Male C57BL/6mice were randomized into3groups:(1) normal group;(2) Methionine and choline-deficient high fat (MCD) group;(3) MCD+TF group. All animals were induced warm ischemia for15minutes, followed by3hours reperfusion. For in vitro study, ROS production of mouse normal and fatty liver isolated hepatocytes, and TNF-a production of LPS-stimulated RAW264.7cells, a mouse macrophage cell line was measured by treated with or without theaflavin, respectively.Results:Liver steatosis, serum alanine amino transferase (ALT), aspartate amino transferase (AST), Thiobarbituric Acid Reactive Substances (TBARS), gene expressions of tumor necrosis factor-a (TNF-a), interleukin6(IL-6), induced nitric oxide synthase (iNOS) and osteopontin (OPN) detected by qRT-PCR and TUNEL-positive cells, F4/80immunostained cells were increased in MCD group, however decreased significantly in MCD+TF group. And in vitro experiment, theaflavin significantly diminished ROS production of steatotic hepatocytes and TNF-α production of LPS-stimulated RAW264.7cells.Conclusion:Fatty livers caused cellular injury through I/R, which was significantly attenuated by theaflavin indicated that theaflavin has protective effects on I/R injury in fatty liver by anti-oxidant, anti-inflammation, and anti-apoptotic mechanisms.