S-adenosyl-L-methionine attenuates oxidative stress and hepatic stellate cell activation in an ethanol-LPS-induced fibrotic rat model

Shock
Amel KaraaLaura W Schrum

Abstract

Previous studies report S-adenosyl-L-methionine (SAMe) can exert hepatoprotective effects. At present, the role of SAMe in affecting the activation and/or proliferation of hepatic stellate cells (HSCs) during alcohol-induced fibrotic disease progression is poorly understood. In the human disease state, chronic ethanol intake increases hepatic exposure to LPS and magnifies the hepatic insult leading to fibrosis and cirrhosis. In this study, we developed a "2-hit" ethanol-LPS fibrotic liver rat model with which to investigate the effects of SAMe as a hepatic antifibrotic treatment. Male rats were maintained on liquid diets containing either ethanol or isocalorically matched controls for 8 weeks. Animals received ethanol alone (E), ethanol concomitant with twice weekly LPS injections (EL), or ethanol, LPS, and daily SAMe injections. When using this model, SAMe-treated animals demonstrated significantly decreased fibrosis, oxidative stress, steatosis, and improved liver function versus the EL group. In addition, the EL group showed increased HSC activation, an effect that was abrogated by the addition of SAMe. Analysis of the transforming growth factor-beta (TGF-beta) signaling pathways demonstrated increased hepatic TGF-beta and S...Continue Reading

References

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Citations

Feb 15, 2011·Therapeutic Advances in Gastroenterology·Thomas H FrazierCraig J McClain
Mar 18, 2009·World Journal of Gastroenterology : WJG·Courtney S SchaffertGeoffrey M Thiele
Mar 20, 2010·World Journal of Gastroenterology : WJG·Gyongyi Szabo, Shashi Bala
Jun 3, 2011·World Journal of Gastroenterology : WJG·Kyle J ThompsonLaura W Schrum
Aug 26, 2011·World Journal of Hepatology·Cathy C MooreLaura W Schrum
Oct 21, 2010·Liver International : Official Journal of the International Association for the Study of the Liver·Ashley M LaknerLaura W Schrum
Oct 28, 2016·Hepatology International·Joaquin Cabezas, Ramon Bataller
Jan 20, 2017·Advanced Pharmaceutical Bulletin·Hossein NiknahadArastoo Saeedi
Jul 30, 2010·Journal of Forensic Sciences·Slobodan NikolićFehim Juković
Jan 13, 2016·World Journal of Gastroenterology : WJG·Moon-Sun KimXianqin Qu
Nov 1, 2017·World Journal of Gastroenterology : WJG·Sukhpreet SinghKusum K Kharbanda
Jul 17, 2008·Shock·Stephen F Lowry
Apr 25, 2020·Journal of Hepatology·Yulia A NevzorovaJordi Gracia-Sancho
Dec 5, 2020·Signal Transduction and Targeted Therapy·Zhanghao LiShizhong Zheng
Apr 6, 2018·Environmental Science & Technology·Andrew E LalooPhilip L Bond
Nov 17, 2009·The International Journal of Biochemistry & Cell Biology·Julio Isael Pérez-CarreónVictoria Chagoya de Sánchez
Jun 8, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Kyle J ThompsonLaura W Schrum
Nov 2, 2011·Therapeutic Advances in Gastroenterology·Michal Cohen-Naftaly, Scott L Friedman

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