Participation of 5-lipoxygenase and LTB4 in liver regeneration after partial hepatectomy.

Autor: Lorenzetti F; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Vera MC; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Ceballos MP; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Ronco MT; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Pisani GB; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Monti JA; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Lucci A; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina.; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Comanzo CG; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Tordjmann T; INSERM U1174, Université Paris Saclay, bât. 443, 91405, Orsay, France., Carrillo MC; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina.; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina., Quiroga AD; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina.; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina.; Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS) Sede Regional Rosario, Universidad Abierta Interamericana, Av. Pellegrini 1618 (S2000BUG), Rosario, Argentina., Alvarez ML; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina. alvarez@ifise-conicet.gov.ar.; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina. alvarez@ifise-conicet.gov.ar.; Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS) Sede Regional Rosario, Universidad Abierta Interamericana, Av. Pellegrini 1618 (S2000BUG), Rosario, Argentina. alvarez@ifise-conicet.gov.ar.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Dec 03; Vol. 9 (1), pp. 18176. Date of Electronic Publication: 2019 Dec 03.
DOI: 10.1038/s41598-019-54652-7
Abstrakt: Regeneration is the unmatched liver ability for recovering its functional mass after tissue lost. Leukotrienes (LT) are a family of eicosanoids with the capacity of signaling to promote proliferation. We analyzed the impact of blocking LT synthesis during liver regeneration after partial hepatectomy (PH). Male Wistar rats were subjected to two-third PH and treated with zileuton, a specific inhibitor of 5-lipoxygenase (5-LOX). Our first find was a significant increment of intrahepatic LTB4 during the first hour after PH together with an increase in 5-LOX expression. Zileuton reduced hepatic LTB4 levels at the moment of hepatectomy and also inhibited the increase in hepatic LTB4. This inhibition produced a delay in liver proliferation as seen by decreased PCNA and cyclin D1 nuclear expression 24 h post-PH. Results also showed that hepatic LTB4 diminution by zileuton was associated with a decrease in NF-ĸB activity. Additionally, decreased hepatic LTB4 levels by zileuton affected the recruitment of neutrophils and macrophages. Non-parenchymal cells (NPCs) from zileuton-treated PH-rats displayed higher apoptosis than NPCs from PH control rats. In conclusion, the present work provides evidences that 5-LOX activation and its product LTB4 are involved in the initial signaling events for liver regeneration after PH and the pharmacological inhibition of this enzyme can delay the initial time course of the phenomenon.
Databáze: MEDLINE
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