Enzymes involved in eicosanoid cascade are differentially expressed during liver regeneration after partial hepatectomy (PH) in rats

LORENZETTI, F; VERA, MC; LUCCI, A; COMANZO, CG; CEBALLOS, MP; CARRILLO, MC; QUIROGA AD; ALVAREZ ML

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Metabolism of arachidonic acid either through the cyclooxygenase(COX-2 or 1) or the 5-lipoxygenase (5-LOX) pathways leads tothe formation of different bioactive eicosanoids: prostanoids (prostaglandinsand tromboxanes) and leukotrienes (LT), respectively.While it has been established that prostaglandins are necessarymediators of liver proliferation during regeneration, the role of LTis not clear. 5-LOX produces LTA4, which is immediately convertedto LTB4 by LTA4 hydrolase (LTA4-H) or LTC4 by LTC4 synthase(LTC4-S). Previous studies from our lab showed that treatment witha 5-LOX inhibitor produces a decrease in LT content and a reductionin liver proliferation after PH in rats, indicating that LT are necessaryfor liver regeneration. Objective: to study the expression of enzymesinvolved in the synthesis of eicosanoids during liver regeneration,focusing on the enzymes of LT biosynthesis. Methods and results:Adult male Wistar rats were subjected to sham surgery or PH (70% liver removal). Liver samples were obtained 1 and 24 h post-surgery.Also, non-parenchymal liver cells (SNPs) were isolated bycollagenase perfusion since 5-LOX and LTA4-H are expressed inthese cells. qPCR studies showed a decrease (-90%*) on LTC4-SmRNA with no changes on 5-LOX or LTA4-H mRNA 1 h post-HP.However, immunoblot analysis showed that 5-LOX protein levels 1hpost-PH were significantly increased in PH rats (+40%*). mRNA expressionsof both 5-LOX and LTC4-S 24h post-PH were significantlyreduced (-75 %* and -90%*, respectively), while COX-2 mRNAwas increased (+200 %*) at that time. This decrease of 5-LOX 24hpost-PH also caused a reduction in intrahepatic LTB4, determinedby ELISA. (*p