Thioacetamide-induced liver regeneration involves the expression of cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes

Background/Aims: A regeneration process intended to restore organ function follows liver hepatotoxicity induced by a necrogenic dose of thioacetamide (TAM). Methods: The expression of genes related to inflammation such as nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) has been analyzed in the course of the regenerative response, using NOS-2 KO mice or animals treated with selective inhibitors of COX-2. Results: All animals lacking both activities survived to the hepatotoxic administration. However, animals deficient for NOS-2 exhibited more severe organ damage in view of the levels of hepatic serum markers of function, as well as an attenuated activation of NF-kappaB. The levels of C/EBPs were determined as markers of hepatocyte de-differentiation and regeneration, and the expression of COX-2 in TAM treated animals was concomitant with a decrease in C/EBP-alpha level. Analysis of cyclin D1, E and PCNA correlated with hepatocytes entering into the S phase of cell cycle by the effect of TAM. Conclusions: These data indicate that hepatocytes from TAM-treated mice express NOS-2 and COX-2 proteins and initiate the regeneration process that follows acute liver injury. However, the absence of NO delays hepatocyte regeneration, whereas COX-2-inhibition appears to decrease liver damage. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.