Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 12, pp 1569–1576 | Cite as

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

  • Mirhan N. Makled
  • Maha H. SharawyEmail author
  • Mohammed S. El-Awady
Original Article


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 and PDFG-BB, with subsequent inhibition of TIMP-1.


Saroglitazar (SGZ) Liver fibrosis Leptin TGF-β1 PDGF-BB TIMP-1 







Peroxisome proliferator-activated receptor


Transforming growth factor-β1


Alpha-smooth muscle actin


Platelet-derived growth factor-BB


Tissue inhibitor of metalloproteinases-1



The authors acknowledge Dr. Walied Abdo, Associate Prof. of Veterinary Pathology, Kafr El Sheikh University, Egypt, for aiding in the histopathological examination.

Author contribution

All authors contributed equally. MM, MS, and ME conceived, designed the research, conducted the experiments, analyzed the data, and wrote the manuscript. All authors read and approved the manuscript.

Compliance with ethical standards

Animal welfare was ensured in accordance with the ethical standards of the “Research Ethics Committee” of the Faculty of Pharmacy, Mansoura University, Egypt, code number (2017-101/2019-20). These institutional standards are in line with “Principles of laboratory Animal Care” (NIH publication No. 85-23, revised 1985).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyMansoura UniversityMansouraEgypt

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