Protective effect of betaine against galactosamine-induced acute liver injury in rats

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>We investigated the protective effect of betaine against galactosamine (GalN)-induced acute hepatic injury. Male rats received betaine from 2 wk prior to GalN treatment. Betaine supplementation inhibited the elevation of serum enzyme activities and the histopathological changes induced by GalN challenge. However, hepatic lipid peroxidation, glutathione levels, and oxidative DNA damage were unaffected by either GalN or betaine treatment. GalN treatment suppressed ornithine decarboxylase (ODC) expression and decreased putrescine levels in liver, both of which were prevented by betaine supplementation. In H4IIE cells, treatment with betaine or <I>S</I>-adenosylmethionine provided complete protection against GalN-induced cytotoxicity. Addition of difluoromethylornithine, an irreversible ODC inhibitor, abolished the protective effect of betaine and <I>S</I>-adenosylmethionine<B>,</B> indicating that depletion of putrescine is critically implicated in GalN-induced cytotoxicity. These results suggest that the beneficial effect of betaine against GalN-induced hepatotoxicity can be attributed to the improvement of polyamine metabolism via elevation of <I>S</I>-adenosylmethionine availability in the liver.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Betaine prevents GalN-induced liver injury both <I>in vivo</I> and <I>in vitro.</I> </LI> <LI> Induction of liver injury by GalN does not involve oxidative stress. </LI> <LI> GalN-induced liver injury is associated with impairment of the polyamine metabolism. </LI> <LI> By increasing SAM, betaine improves the polyamine metabolism dysregulated by GalN. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>