CREB1 and PPAR-α/γ Pathways in Hepatic Ischemia/Reperfusion: Route for Curcumin to Hepatoprotection

Enver Ahmet Demir; Okan Tutuk; Hatice Dogan-Gocmen; Duygu Seren Ozyilmaz; Meryem Ilkay Karagul; Mikail Kara; Muhyittin Temiz; Cemil Tumer

doi:10.5812/ijpr-133779

CREB1 and PPAR-α/γ Pathways in Hepatic Ischemia/Reperfusion: Route for Curcumin to Hepatoprotection

Iran J Pharm Res. 2023 Feb 1;21(1):e133779. doi: 10.5812/ijpr-133779. eCollection 2022 Dec.

Authors

Enver Ahmet Demir¹, Okan Tutuk¹, Hatice Dogan-Gocmen¹, Duygu Seren Ozyilmaz¹, Meryem Ilkay Karagul², Mikail Kara², Muhyittin Temiz³, Cemil Tumer¹

Affiliations

¹ Department of Physiology, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey.
² Department of Histology and Embryology, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey.
³ Department of General Surgery, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey.

Abstract

Background: Hepatic ischemia/reperfusion injury is a major problem that can exacerbate complications, particularly in liver transplantations.

Objectives: This study aimed to investigate the cellular mechanisms of ischemia/reperfusion injury and hepatoprotection by curcumin.

Methods: Wistar albino rats were divided into four groups as Control, Sham, I/R, and Cur+I/R. Hepatic ischemia/reperfusion was induced in I/R and Cur+I/R animals, the latter of which was also given 50 mg/kg/day of curcumin for 14 days. Liver aminotransferases and the transcription regulators of inflammation (RelA, IκB, PPAR-α, PPAR-γ, CREB1) were examined along with the histological examination.

Results: Hepatic ischemia/reperfusion was found to disrupt hepatic microstructure and downregulate PPAR-α, PPAR-γ, and CREB1 transcripts. Curcumin supplementation in hepatic ischemia/reperfusion recovered the structural organization and promoted the hepatocyte regeneration while increasing expressions of PPARs and CREB1. RelA and IκB were found unaltered, possibly due to the crosstalk between targeted transcripts by ischemia/reperfusion and curcumin.

Conclusions: In sum, PPAR-α/γ and CREB1 were involved in hepatic ischemia/reperfusion and, moreover, were detected to be stimulated by curcumin. PPAR and CREB pathways were found to provide a route to hepatoprotection for curcumin supplementation as evidenced by the microstructural improvement.

Keywords: CREB; Curcumin; Inflammation; Ischemia/Reperfusion; Liver; PPAR.