Aleglitazar treats non-alcoholic steatohepatitis in mice through PPAR dependent pathway

Document Type : Original Article


Pharmacology departement, Faculty of medicine, zagazig university, Cairo, Egypt


Background: Non-alcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease, a more severe form of NAFLD is non-alcoholic steatohepatitis (NASH). Hepatic injury in NASH is caused by oxidative stress and inflammation brought on by lipotoxicity. Aleglitazar is a dual peroxisome proliferator-activated receptor (PPAR) agonist which has anti-inflammatory, antioxidant, and anti-apoptotic effects Aim: To investigate the possible curative effect of Aleglitazar against NASH as well as the possible involvement of PPAR in this effect Methods: NASH was induced using high-fat diet. Mice received Aleglitazar (10 mg/kg/day), Aleglitazar (10 mg/kg/day, i.p.)+ PPAR- γ blocker (GW-9962) (1mg/kg/day, i.p.) and Aleglitazar (10 mg/kg/day, i.p.) + PPAR-α blocker (MK-886) (10 mg/kg/day, i.p.) for 6 weeks. Blood samples were taken for analysis of alanine and aspartate transaminases (ALT&AST), tumor necrosis factor (TNF-α), matrix metalloproteinase-1 (MMP-1), adiponectin, cholesterol, high-density lipoprotein (HDL), and triglyceride levels. At the same time, the livers of the mice were removed for light microscopic examination and the detection of reduced glutathione (GSH) content Results: Increases in triglyceride, cholesterol, MMP-1, TNF- α, AST, ALT, and triglyceride levels were observed in NASH animals, whereas reductions in HDL, adiponectin, and GSH content were observed along with vesicular steatosis, lobular inflammation, and hepatocyte ballooning and degeneration. Aleglitazar treatment improved histopathological alterations and lowered MMP-1, TNF- α, AST, ALT, triglyceride, and cholesterol levels while increasing HDL, adiponectin, and GSH levels. The use of GW-9662 and MK-886 significantly abrogated the hepatic protective effect of Aleglitazar as well as reduced the anti-inflammatory and antioxidant effects


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