The dual PPAR-α/γ agonist saroglitazar ameliorates thioacetamide-induced liver fibrosis in rats through regulating leptin.

Naunyn-Schmiedeberg's Archives of Pharmacology
Mirhan N MakledMohammed S El-Awady

Abstract

Liver fibrosis is a challenging global health problem resulting from chronic liver injury with no treatment currently available. It has been shown that activators for different peroxisome proliferator-activated receptor (PPAR) isoforms (α, γ, and δ) can affect different pathways in liver fibrosis. To evaluate the effects of the dual PPAR-α/γ agonist saroglitazar (SGZ) against thioacetamide (TAA)-induced fibrosis in rats, SGZ was administered for 6 weeks together with TAA injection. Administration of SGZ ameliorated TAA-induced elevation in hepatic biomarkers. SGZ was able to inhibit periportal and intralobular fibrous connective tissue proliferation, to decrease hydroxyproline content, and to lower alpha smooth muscle actin (α-SMA) protein expression. To unearth the antifibrotic mechanism of SGZ, the role of several fibrotic markers was studied. SGZ possesses inhibitory effect on protein levels of leptin, transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). Furthermore, SGZ rectified matrix degradation through decreasing tissue inhibitor of metalloproteinases-1 (TIMP-1). This study suggests that SGZ could have a possible antifibrotic effect via suppression of leptin that can repress TGF-β1...Continue Reading

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Citations

Aug 14, 2020·Stem Cell Reviews and Reports·Richard P Halley-StottNonhlanhla P Khumalo
Nov 23, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jinfu ChenWeimin Zhu
Jun 26, 2021·Drug Design, Development and Therapy·Jingjing LiJianye Wu
Jul 31, 2021·Gastroenterology Research and Practice·Jingguo Li, Biguang Tuo
Aug 28, 2021·International Journal of Molecular Sciences·Pierre LayrolleStéphane Chavanas

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