Role of Na+‐K+‐ATPase in development of alcoholic fatty liver disease

Abstract

Patients with alcoholic fatty liver disease (AFLD) were well‐known to have low blood sodium level. Alcohol intoxication causes low blood sodium level. In the previous study, we obtained that acute and chronic alcohol consumption induced the phenomenon of low blood sodium level in rats. These findings suggested renal failure, but there was no change in renal function in human and rat. Blood sodium level is regulated by Na+‐K+‐ATPase in lots of tissues. Then, we hypothesized that regulation of Na+‐K+‐ATPase may contributes to improve the development of alcoholic organ damage. In the present study, we focused to clarify whether regulation of regulation of Na+‐K+‐ATPase improves alcoholic liver injury in rats or not. Alcoholic fatty liver disease rat model was performed by feeding a Lieber‐DeCalri diet for 4 weeks. Amiloride, lidocaine, ouibain, sanguinarine, or glibenclamide was administered i.p to rats for 2 weeks after feeding an alcohol diet. After 4 weeks feeding, blood biochemical tests were performed. Expression of mRNA and proteins was performed by qPCR and western blotting analysis. EMSA was performed. Histopathological findings showed alcoholic fatty liver changes in the liver of rats fed the alcohol diet On the other hand, administration of inhibitors of Na+‐K+‐ATPase reduced a slight improvement and decreased the NF‐kappaB activity via IRF3‐dependent pathway but increased activation of IRFy‐dependent pathway in the liver, which phenomena spotlighted in the isolated endsome from the liver, leading that Na+‐K+‐ATPase in endosome can be related to activation of innate immune system. These findings suggest that regulation of Na+‐K+‐ATPase may be one of therapies for alcoholic fatty liver disease.Support or Funding InformationThis research was supported in part by JSPS KAKENHI Grant Number 24390175.