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Liver X Receptor Inverse Agonist SR9243 Suppresses Nonalcoholic Steatohepatitis Intrahepatic Inflammation and Fibrosis

Liver X Receptor Inverse Agonist SR9243 Suppresses Nonalcoholic Steatohepatitis Intrahepatic Inflammation and Fibrosis

Peng Huang, Benson Kaluba, Xiao-Lin Jiang, Shi Chang, Xiao-Feng Tang, Lin-Feng Mao, Zhi-Peng Zhang, Fei-Zhou Huang

Biomed Res Int. 2018 Feb 18;2018:8071093.

PMID: 29670908

Abstract:

Abnormal metabolism of cholesterol may be a contributing factor in nonalcoholic steatohepatitis (NASH) pathogenesis. Accumulating evidence has shown that liver X receptor (LXR) is closely related to intrahepatic inflammation and fibrosis. In this study, we evaluated the effects of a novel liver-specific LXR inverse agonist, SR9243, on antifibrosis in NASH mice. A high-cholesterol diet was employed to induce NASH in BALB/c mice by either carbon tetrachloride (CCL4) administration or bile-duct ligation (BDL). Once NASH was induced, mice were treated with SR9243 for one month by intraperitoneal (i.p.) injection. Liver tissues were collected to determine the degree of fibrosis and intrahepatic inflammation via pathological examination and QPCR; serum was collected to analyze the plasma lipid levels and liver function by clinical biochemistry. The mice developed hepatic steatosis, severe hepatic inflammation, and fibrosis by BDL or CCL4. Treatment with SR9243 significantly reduced the severity of hepatic inflammation and ameliorated hepatic fibrosis; simultaneously, body weight, serum glucose, and plasma lipid levels were controlled effectively. Our data demonstrate that SR9243 exerts an antifibrotic and anti-inflammatory effect in NASH mice; hence these findings highly suggest that LXR inverse agonist could be therapeutically important in NASH treatment.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1613028811	SR9243		1613028-81-1	Price

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