The Role of Peroxisome Proliferator‐Activated Receptor-Gamma (PPARγ) In Drug-Induced Hepatotoxicity: A Narrative Review

Abstract

Background: Drug-induced hepatotoxicity is an acute or chronic liver damage due to drugs or herbals. Its diagnosis is difficult since the presentation is similar to various hepatobiliary disorders. It is one of the major reasons for drug failures at clinical phases of drug-development and withdrawal from the market. Peroxisome proliferator‐activated receptors (PPARs) are transcription factors that belong to the nuclear hormone receptor superfamily; comprising PPARα, PPARγ and PPARβ/δ. They have different distribution and expression profiles, and this leads to different clinical outcomes. This review focuses on the protective role of the PPARγ in liver damage giving special emphasis to drug-induced hepatotoxicity.

Methods: This narrative review employed a systematic search strategy to identify relevant literature on the role of PPARγ in drug-induced hepatotoxicity. We searched major academic databases such as PubMed, Elsevier, EMBASE, Web of Science, and Google Scholar databases using a combination of keywords related to PPARγ, drug-induced liver injury (DILI), and hepatotoxicity. We included original research articles, reviews, and meta-analyses published in English without time bound. The retrieved articles were critically appraised for their methodology, quality of evidence, and relevance to the topic of interest.

Result and Conclusion: Ligands acting on PPARγ showed hepatoprotective activity and this protective effect is mediated through activation of Nrf2 and enhancing PPARγ mRNA expression. Further studies are recommended to understand the molecular mechanisms of hepatoprotective agents acting on PPARγ.