Abstract | BACKGROUND & AIMS: METHODS & RESULTS: HepG2 cells treated with palmitic acid (PA;0.75 mM) showed decreased expression of various antioxidant biomarkers (SOD1, SOD2, glutathione peroxidase and catalase) and increased expression of inflammatory markers (TNFα, IL1β and IL6). These effects were blocked by saroglitazar, pioglitazone and fenofibrate (all tested at 10μM concentration). Furthermore, these agents reversed PA-mediated changes in mitochondrial dysfunction, ATP production, NFkB phosphorylation and stellate cell activation in HepG2 and HepG2-LX2 Coculture studies. In mice with choline-deficient high-fat diet-induced NASH, saroglitazar reduced hepatic steatosis, inflammation, ballooning and prevented development of fibrosis. It also reduced serum alanine aminotransferase, aspartate aminotransferase and expression of inflammatory and fibrosis biomarkers. In this model, the reduction in the overall NAFLD activity score by saroglitazar (3 mg/kg) was significantly more prominent than pioglitazone (25 mg/kg) and fenofibrate (100 mg/kg). Pioglitazone and fenofibrate did not show any improvement in steatosis, but partially improved inflammation and liver function. Antifibrotic effect of saroglitazar (4 mg/kg) was also observed in carbon tetrachloride-induced fibrosis model. CONCLUSIONS:
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Authors | Mukul R Jain, Suresh R Giri, Bibhuti Bhoi, Chitrang Trivedi, Akshyaya Rath, Rohan Rathod, Ramchandra Ranvir, Shekhar Kadam, Hiren Patel, Prabodha Swain, Sib Sankar Roy, Nabanita Das, Eshani Karmakar, Walter Wahli, Pankaj R Patel |
Journal | Liver international : official journal of the International Association for the Study of the Liver
(Liver Int)
Vol. 38
Issue 6
Pg. 1084-1094
(06 2018)
ISSN: 1478-3231 [Electronic] United States |
PMID | 29164820
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2017 Cadila Healthcare Ltd., Liver International Published by John Wiley & Sons Ltd. |
Chemical References |
- Biomarkers
- PPAR alpha
- Phenylpropionates
- Pyrroles
- Tumor Necrosis Factor-alpha
- saroglitazar
- Aspartate Aminotransferases
- Alanine Transaminase
- Fenofibrate
- Pioglitazone
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Topics |
- Alanine Transaminase
(blood)
- Animals
- Aspartate Aminotransferases
(blood)
- Biomarkers
(blood)
- Diet, High-Fat
- Fenofibrate
(pharmacokinetics)
- Hep G2 Cells
- Humans
- Kupffer Cells
(drug effects)
- Liver
(pathology)
- Male
- Mice
- Mice, Inbred C57BL
- Non-alcoholic Fatty Liver Disease
(drug therapy, pathology)
- PPAR alpha
(agonists)
- Phenylpropionates
(pharmacology)
- Pioglitazone
(pharmacology)
- Pyrroles
(pharmacology)
- Tumor Necrosis Factor-alpha
(blood)
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