Inhibition of Heme Oxygenase Antioxidant Activity Exacerbates Hepatic Steatosis and Fibrosis In Vitro

Antioxidants
Marco RaffaeleLuca Vanella

Abstract

The progression of non-alcoholic fatty liver disease (NAFLD) and the development of hepatic fibrosis is caused by changes in redox balance, leading to an increase of reactive oxygen species (ROS) levels. NAFLD patients are at risk of progressing to non-alcoholic steatohepatitis (NASH), associated to cardiovascular diseases (CVD), coronary heart disease and stroke. Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. The present work was directed to determine whether use of an inhibitor of HO-1 activity affects lipid metabolism and fibrosis process in hepatic cells. Oil Red assay and mRNA analysis were used to evaluate the triglycerides content and the lipid metabolism pathway in HepG2 cells. ROS measurement, RT-PCR and Soluble collagen assay were used to assess the intracellular oxidant, the fibrosis pathway and the soluble collagen in LX2 cells. The activity of HO-1 was inhibited using Tin Mesoporphyrin IX (SnMP). Our study demonstrates that a non-functional HO system results in an increased lipid storage and collagen release in hepatocytes. Consequently, an increase of HO-1 levels may provide a therapeutic approach to address the metabolic alterations associated...Continue Reading

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Citations

Jan 30, 2020·International Journal of Molecular Sciences·Claudia G FrestaGiuseppe Caruso
Dec 19, 2020·International Journal of Molecular Sciences·Valeria SorrentiLoredana Salerno
Dec 18, 2020·International Journal of Molecular Sciences·David E Stec, Terry D Hinds
Aug 4, 2021·Physiological Reports·Luma MeloJames E Klaunig

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Methods Mentioned

BETA
PCR

Software Mentioned

Muse Cell Analyzer Muse analysis

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