Role of cyclooxygenase isoforms in encephalopathy of cirrhotic rats

Abstract

BackgroundHepatic encephalopathy (HE) is a complex neuropsychiatric syndrome secondary to acute or chronic liver failure. However, its pathophysiology remains obscure. Recently, we found that the inhibition of cyclooxygenase by indomethacin aggravated HE in rats with thioacetamide-induced acute hepatic failure, suggesting a pivotal role of cyclooxygenase in HE. This study was aimed at surveying the roles of cyclooxygenase isoforms responsible for prostaglandins synthesis, cyclooxygenase-1 (COX1) and COX2, in cirrhotic rats with HE. MethodsLiver cirrhosis was induced (using formalin) in male Sprague–Dawley rats with bile duct ligation (FBDL). Sham-operated rats served as the surgical controls. The severity of HE was assessed by motor activity counts. Plasma 6-keto-prostaglandin-F1α [6-keto-PGF1α; a relatively stable metabolite of prostacyclin (PGI2)], alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALK-P), and total bilirubin were measured. Hepatic mRNA expressions of COX1 and COX2 were tested. ResultsThe FBDL group showed lower motor activity counts than the sham group in total (1472 ± 156 vs. 2174 ± 262 counts/30 min, p = 0.034), ambulatory (824 ± 99 vs. 1443 ± 206 counts/30 min, p = 0.014), and vertical movement (431 ± 69 vs. 849 ± 145 counts/30 min, p = 0.018). The mRNA expression of hepatic COX2 was significantly higher in the FBDL group. Plasma ALK-P and bilirubin levels were negatively correlated with total movements, respectively (both p < 0.05). In addition, hepatic COX2 mRNA expression was positively correlated with AST, ALK-P, total bilirubin, and 6-keto-PGF1α (all p < 0.05), but not correlated with total movements. ConclusionHepatic COX2 expression and PGI2 production are enhanced in cirrhotic rats, but the correlation with HE is not remarkable. Cyclooxygenase and PGI2 may not play important roles in HE in the setting of chronic liver failure.