Pterostilbene ameliorates the disrupted Adars expression and improves liver fibrosis in DEN-induced liver injury in Wistar rats: A novel potential effect.

Abstract

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.