The combination of S-adenosylmethionine and dilinoleoylphosphatidylcholine attenuates nonalcoholic steatohepatitis produced by a high-fat diet in rats

In the pathogenesis of nonalcoholic steatohepatitis (NASH), oxidative stress resulting from free radicals generated by cytochrome P4502E1 (CYP2E1) plays a major role suggesting the importance of antioxidants. The objective of this study was to assess in a high-fat (HF) diet rat model the effects of the combination of S-adenosylmethionine (SAMe) plus dilinoleoylphosphatidylcholine (DLPC) in the treatment of NASH. To test the hypothesis that these 2 antioxidants are beneficial in NASH, male Sprague-Dawley rats were fed 5 different diets for 6 weeks: control, HF diet and HF plus, SAMe, and DLPC or their combination. As expected, the HF diet significantly increased hepatic triacylglycerols and CYP2E1 levels. However, only the combination diet opposed this effect, consistent with different actions of the 2 antioxidants. Next, 24 additional rats divided in 2 groups were fed the HF or the HF + SAMe + DLPC diets for 3 weeks. Dietary intake was similar, but liver triacylglycerols dropped from 76.1 ± 6.8 to 49.4 ± 3.5 mg/g (P = .002), and hepatic CYP2E1 messenger RNA (mRNA) decreased after treatment (P = .01), with a trend for less CYP2E1 protein. This was accompanied by a 41% reduction of hepatic 4-hydroxynonenal (P = .008), reflecting control of oxidative stress. Furthermore, the hepatic inflammatory cytokine tumor necrosis factor α mRNA and tumor necrosis factor α protein decreased (P = .05 and P = .01, respectively) with attenuation of α1(I) procollagen mRNA and type I collagen levels (P = .01 and P = .02, respectively). We concluded that the combination SAMe + DLPC might be beneficial in NASH by reducing oxidative stress and associated liver injury.