S‐Adenosylmethionine Administered Orally Protects Against Steatohepatitis in a Model

Objectives Nonalcoholic steatohepatitis (NASH) may accompany obesity and parenteral nutrition. There is no FDA approved therapy available. This study evaluated the efficacy of S‐Adenosylmethionine (SAMe), an antioxidant that is involved in the hepatic transsulfuration pathway, as treatment modality in a dietary model for NASH. Methods Rats were fed: (1) amino acid based methionine choline sufficient (MCS), or (2)deficient (MCD) diets. After 3 weeks, rats on deficient diet were further treated orally via gavage with: (A) SAMe, or (B) vehicle (MCD). Five weeks after initiation of study samples were collected and gene profiles analyzed by RT‐PCR. Results Animals fed deficient diet (MCD) did not gain weight. Liver enzymes, aspartate and alanine aminotransferase were significantly elevated in MCD animals (p<0.001). SAMe treatment normalized these enzyme activities. MCD rats developed severe steatohepatitis manifested with steatosis, inflammation and necrosis (p<0.001), which was improved with SAMe therapy (p<0.05). Blood level of reduced GSH significantly decreased in MCD rats and therapy attenuated this abnormality p<0.001). There was a significant overexpression of genes involved in inflammation, tissue remolding and fibrosis in livers from rats fed MCD diet. Treatment significantly improved these gene profiles. Conclusion Oral administration of SAMe protects against steatohepatitis by improving liver pathology and expression of deleterious genes. These data support the use of SAMe therapy in NASH/NAFLD patients. This study was supported by NIH grant AT1490‐01A1 (H. Oz).