Highly Purified Eicosapentaenoic Acid Ethyl Ester Prevents Development of Steatosis and Hepatic Fibrosis in Rats

Abstract

EPA-E prevents progression of hepatic fibrosis in an MCD-induced NASH model with reduction of oxidative stress, inflammation, and initial hepatic steatosis. Thus, EPA-E treatment may be a potential therapy to treat NASH.

Eicosapentaenoic Acid Attenuates Progression of Hepatic Fibrosis with Inhibition of Reactive Oxygen Species Production in Rats Fed Methionine- and Choline-Deficient Diet

“…The MCD diet and the methionine-and choline-sufficient (MCS) diet were obtained from Dyets Inc. (#518810 and #518811, respectively; Bethlehem, PA). The composition of each diet is detailed in our previous report [30].…”

“…TG levels were determined using a commercial kit (Triglyceride E-test Wako; Wako Pure Chemical Industries). Hepatic TGF-b1 levels were measured by EIA as previously described [30].…”

“…We have previously reported that EPA prevents the development of hepatic fibrosis in a NASH model using methionine-and choline-deficient (MCD) diet [30]. In that study, EPA ethyl ester (EPA-E) was administered from onset of steatohepatitis induction, thus the therapeutic effect of EPA against hepatic fibrosis has not been clarified.…”

Eicosapentaenoic acid attenuates hepatic accumulation of cholesterol esters but aggravates liver injury and inflammation in mice fed a cholate-supplemented high-fat diet

“…In addition, EPA administration could also ameliorate liver injury and fibrinogenesis occurring in experimental fatty liver models (Kajikawa et al, 2010;Svegliati-Baroni et al, 2006). Larter et al (2008a) have shown that fish oil prevents fatty liver but not hepatic injury and enhances oxidative responses in the liver of mice fed a methinone-and choline-deficient diet.…”

“…We also consider that EPA causes deleterious effects on fatty liver injury when CE synthesis predominantly occurs and plays a protective role as shown by the mice fed the CAHF diet. The effect of EPA or n-3-PUFA-rich fish oil has so far been examined using the fatty liver models associated with fatty liver due to TG accumulation (Hein et al, 2010;Jung et al, 2011;Kajikawa et al, 2009Kajikawa et al, , 2010Larter et al, 2008a;Sekiya et al, 2003;Svegliati-Baroni et al, 2006;Tanaka et al, 2010;Yamazaki et al, 2007). Further studies are necessary to define the relationship between the type of lipid accumulated in the liver and the effect of EPA or n-3-PUFA-rich fish oil on liver injury.…”