The Effect of Glutathione On Experimental Rat With Fatty liver And Its Possible Molecular Mechanism / 重庆医科大学学报

ABSTRACT

Objective: To investigate the role of uncoupling protein -2 in development of nonalcoholic fatty liver diseases ( NAFLD) ,and explore the effect of glutathione ( GSH) on NAFLD. Methods: 32 SD rats were randomly divided into basic diet - treated group ( B group) ,model group( M group) , Pathology group( P group) and GSH treated group( G group). The following parameters were determined by biochemical analysis; superoxide dismutase( SOD) , glutathione(GSH) , malondialdehyde (MDA). Liver histopathologic e-valuation was performed by hematoxylin - eosin staining. Serum tumor necrosis factor alpha(TNF?) level was done by enzyme -linked immunoadsordent assay ( ELISA). Ucp2 and TNFaproteins expression in hepatocytes was examined by immunohistochemistry, and UCP2mRNA expression by semi - quantitative reverse transcription - polymerase chain reaction( RT - PCR). Results: ( 1 ) compared with B group, no evident increase in liver MDA,SOD and GSH of M group rats as well as serum TNF?level were observed. Neither marked change in number of hepatocytes with TNF?positive was shown by immunohistochemistry staining, but an increase in UCP2 mRNA and UCP2 protein expression was seen in M group rats. (2) Compared with M group, a significant increase in serum TNF? and MDA levels was found in P group .while a significant decrease in liver homogenate SOD and GSH was observed . An apparent increase in number of hepatocytes with TNF?and UCP2 positive was shown by immunohistochemistry staining, as well as UCP2mRNA level by RT-PCR. (3) Compared with P group, a significant decrease in serum MDA and a significant increase in liver homogenate SOD, GSH levels was found in G group. A little lower level of UCP2 expression was shown in G group than in P group. Conclusion; High level of serum and tissue TNFaand UCP2 over - expression are concomitant with an extreme decrease even depletion in the liver ATP in NAFLED model rats, that cause oxidative stress and lipid super - oxidation in liver, and induce or exacerbate fatty liver disease progression to steatohepatitis even fibrosis. Glutathione seems to be effective to some extent for NAFLD by protection of liver function through replenishment of exogenous antioxidants.