The Research About The Inhibitory Effect Of Fructose-1,6-diphosphate On Alcohol-Induced Liver Injury

BackgroundAlcoholic liver disease(ALD)is characterized by the liver injury and results from ethanol-induced oxidative stress.The early stage of it is usually characterized by fatty liver,and can be gradually developed into alcoholic hepatitis,liver fibrosis and cirrhosis.FDP(fructose-1,6-diphosphate),a glycolytic intermediate,has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils.It was also reported that FDP can activate the pentose phosphate pathway(PPP)for anaerobic ATP production.In addition,FDP was found to maintain cellular levels of glutathione and catalase as well as upregulating the activity of glucose-6-phosphate dehydrogenase.So we present a study about the inhibitory mechanism of FDP on alcohol-induced liver injury.ObjectiveThe research from biochemical and histopathologic observation explored the inhibitory effect of FDP on acute alcohol liver injury in mice,and analyzed the possible mechanisms.MethodSerum ALT and AST activities and TG level were measured by colorimetry,to observe the effect of FDP on acute alcoholic liver injury;liver MDA and activities of a series of antioxidant enzymes were measured to observe effects of FDP on peroxidation and antioxidant ability;hepatic CYP2E1 was detected by immunohistochemistry,ELISA was used to measure the level of liver aldehyde dehydrogenase(ALDH),serum alcohol dehydrogenase(ADH)activity was measured by colorimetry;we use MTT to measure FDP's effect on cell viability;using flow cytometry to detect the FDP's effect on to alcohol-induced cell apoptosis;pro-caspase3 and cleaved PARP protein level in liver were detected by western blot;using HE staining to analyze the protective effect of FDP.ResultsWe found that 1)FDP does-dependently decrease the increase of serum activity of ALT and AST and TG level;2)The HE staining result showed that FDP could reduce the morphological changes of liver tissue induced by alcohol;3)FDP had a significant effect on the recovery of the cells stimulated by alcohol and inhibit cell apoptosis;4)FDP can dose dependently inhibit lipid peroxidation and oxidative stress reaction;5)FDP can stimulate alcohol metabolism by increasing the activity of ADH and the content of ALDH,and inhibited metabolism activation of alcohol through reducing the level of CYP2E1 protein.ConclusionFDP,as a kind of intermediate product of glycolysis,can prevent liver injury by inhibiting oxidative stress and stimulating alcohol metabolism.