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07 Dec 2021 (Vol 44 , Iss 06 )

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31 Dec 2021 (Vol 44 , Iss 06 )

Journal ID : TMJ-06-09-2021-10640
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Title : Roles of Fenofibrate and Simvastatin on Non-Alcoholic Fatty Liver Disease (NAFLD) in HepG2 Cells

Abstract :

Fenofibrate and simvastatin are drugs that might have beneficial effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to determine the effect of fenofibrate and simvastatin treatment in an NAFLD model. HepG2 cells (5 × 105 cells/well) were treated with oleic acid (OA) or palmitic acid (PA) and various concentrations of either fenofibrate or simvastatin for 24 h (n=4). Histological features were examined by oil-red-O staining. Expression of metabolic genes (peroxisome proliferator activated receptors- α and γ, sterol regulatory element binding proteins-1a and 1c, acetyl-CoA carboxylase, acyl-CoA oxidase, and fatty acid synthase), antioxidative genes (catalase and superoxide dismutase-1 and 2), and cytochrome P450 genes (CYP1A2, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP4A11), was analyzed by RT/qPCR. Accumulation of intracellular lipid was attenuated by 10 and 30 μM fenofibrate while cell shrinkage was observed from the lowest concentration of simvastatin. Expression of metabolic genes was elevated by both OA and PA while fenofibrate and simvastatin reduced expression of these genes in a dose- dependent manner. OA and PA reduced expression of antioxidative genes while fenofibrate increased SOD1 expression and simvastatin restored SOD2 expression. Expression of CYPs was concentration-dependently modified by both drugs compared to the induction group. Our in vitro OA or PA-induced NAFLD model revealed the ability of fenofibrate to control the progression of NAFLD and the tendency of simvastatin to limit the process of NAFLD. These findings suggest that fenofibrate, not simvastatin, provides the potential activity for NAFLD treatment.

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