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    CREB1 and PPAR-?/? Pathways in Hepatic Ischemia/Reperfusion: Route for Curcumin to Hepatoprotection
    (Briefland, 2022) Demir, Enver Ahmet; Tutuk, Okan; Dogan-Gocmen, Hatice; Ozyilmaz, Duygu Seren; Karagul, Meryem Ilkay; Kara, Mikail; Temiz, Muhyittin
    Background: Hepatic ischemia/reperfusion injury is a major problem that can exacerbate complications, particularly in liver trans-plantations. Objectives: This study aimed to investigate the cellular mechanisms of ischemia/reperfusion injury and hepatoprotection by cur -cumin. 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, I & kappa;B, PPAR-& alpha;, PPAR-& gamma;, CREB1) were examined along with the histological examination. Results: Hepatic ischemia/reperfusion was found to disrupt hepatic microstructure and downregulate PPAR-& alpha;, PPAR-& gamma;, 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 I & kappa;B were found unaltered, possibly due to the crosstalk between targeted transcripts by ischemia/reperfusion and curcumin. Conclusions: In sum, PPAR-& alpha;/& gamma; and CREB1 were involved in hepatic ischemia/reperfusion and, moreover, were detected to be stim-ulated by curcumin. PPAR and CREB pathways were found to provide a route to hepatoprotection for curcumin supplementation as evidenced by the microstructural improvement.

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