Protective Effects Of Curcumin On Ethanol-Induced Chronic Liver Injury

Part1Protective Effects of Curcumin on Oxidative DamageInduced by Ethanol in Rat Primary HepatocytesObjective: To establish alcoholic liver injury model in Sparague-Dawley rat primaryhepatocytes, and study the protective effects of curcumin on oxidative damage induced byethanol.Methods:1. Rat primary hepatocytes were treated with ethanol of different dosage (0-200mmol/L) for8h, or100mmol/L in different time (0-24h) to detect cell viability (LDH,AST levels) and oxidative/antioxidative system (MDA, GSH and SOD levels).2. On the basis of this, the hepatocytes were pre-treated with curcumin of differentdoses (0-50μmol/L) for1h, or15μmol/L in different time (0-5h) before ethanol exposure(100mmol/L,8h).Then detect LDH, AST, MDA, GSH and SOD levels.3. Extract the hepatocellular microsomes by gradient centrifugation and detect theHO-1enzyme activity.Results:1. There is remarkable increase of LDH and AST levels along with the increase ofethanol dosage and the extend of the time, as well as MDA formation in hepatocytes, and adecrease of GSH and SOD in ethanol group, it is significant difference at the dosage of100mmol/L or the time of8h (P <0.05).2. Compared with the alcohol group, pre-treatment of curcumin could significantlyprohibit the release of AST and LDH, the rise of MDA level and the decline of SODactivities and GSH content of hepatocytes exposed to ethanol (P <0.05).3. Compared with the control group, pre-treatment of curcumin could improve theprotein level and enzyme activity of HO-1at the dose of15μmol/L and time for1h.Conclusions: Ethanol-induced oxidative damage may occurred in rat primary hepatocytesat dose-and time-dependent manner. Curcumin could prevent its damage, as well asup-regulate HO-1protein expression and improve its enzyme activity. Part2Effects of Curcumin on Chronic Alcoholic Liver Injuryin BALB/c MiceObjective: To establish chronic alcoholic liver injury model in BALB/c mice, andinvestigate the protective effects of curcumin on oxidative damage.Methods:1. BALB/c mice were randomly divided into4groups (A: normal control group,B: curcumin group, C: ethanol group and D: ethanol+curcumin group), the chronicalcoholic liver injury model was established with gradient dosages of ethanol exposure by6weeks (from2.4g/kg/day to4g/kg/day). Group B and D were administered with curcuminof75mg/kg/day.2. Blood samples and liver tissues were collected at the end of the experiment, thehistopathological changes of the liver were observed, the enzyme activity of ALT, AST inserum and plasma levels of TC, TG, HDL-C were determined.3. The content of ROS in liver tissues was determined, as well as the level of T-AOC,GSH, GPx, GST and MDA.Results:1. The body weight gain in group A and B were significant higher than the othertwo groups (P <0.05), but no significant differences were found among group C and D (P>0.05).2. Compared with the control group, ethanol exposure significantly elevated the levelof serum AST, ALT, TC and TG (P>0.05), decline the level of HDL-C (P>0.05), andlipid droplet accumulation were observed. These were attenuated by curcuminsupplementation.3. Compared with the control group, ethanol exposure resulted in liver ROS generation,T-AOC, GSH, GPx and GST depletions and MDA elevention (P <0.05), which weresignificantly reversed by curcumin supplementation.Conclusion: Curcumin supplementation could alleviate pathological changes in the liverand hepatic enzymes release, attenuate the lipid disorder, improve antioxidant enzymeactivity and protect liver from ethanol-induced oxidative stress damage.