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The knowledge of RNA editing modifications and its subsequent proteomic diversity in is still limited and represents only the tip of the iceberg. Adenosine to inosine (A-to-I) RNA editing is the most prevalent in RNA editome with a rising role for ADARgene family as a major regulator of the dynamic landscape of RNA editing. This study aimed at evaluating the potential chemopreventive effects of the epigenetic regulator "pterostilbene" in diethylnitrosamine (DEN)-exposedrat model. Consequently, the hepatic Adars expression was investigated as a possible mechanism for mediation of the putative pterostilbene-induced chemopreventive effect. The effects of administration of pterostilbene were investigated on the structural changes, immunohistochemical staining, liver function test, serum alpha feto-protein (AFP), IL-6, and hepatic Adar1 and Adar2 relative gene expression at the beginning and at the 6th week of the study. Pterostilbene attenuated DEN-induced liver injury, improves hepatocyte parrafin-1 (Hep Par-1), decreases heat shock protein 70 (HSP70), improved AFP, serum albumin, transaminases, IL-6 with alleviation of disturbed hepatic Adar1 and Adar2 expression. This study spotlights the role of pterostilbene in attenuation of DEN-induced liver injury which could be mediated, at least partially, through the alleviation of the aberrant expression of Adar enzymes. Yet, more in-depth studies are needed to further elucidate the molecular mechanisms underlying the effects of pterostilbene on RNA editing enzymes., (Copyright © 2021 Elsevier B.V. All rights reserved.)