title: Role of cyclooxygenase isoforms in encephalopathy of cirrhotic rats.
abstract: BACKGROUND
  Hepatic 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.
  
  
  METHODS
  Liver 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Hepatic COX2 expression and PGI2production are enhanced in cirrhotic rats, but the correlation with HE is not remarkable. Cyclooxygenase and PGI2may not play important roles in HE in the setting of chronic liver failure.
authors: Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department and Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors: Hsin-Ling
authors: HL
authors: Ho
authors: Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department and Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors: Shao-Jung
authors: SJ
authors: Hsu
authors: Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors: Fa-Yauh
authors: FY
authors: Lee
authors: Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: hchuang2@vghtpe.gov.tw.
authors: Hui-Chun
authors: HC
authors: Huang
authors: Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department and Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors: I-Fang
authors: IF
authors: Hsin
authors: Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department and Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors: Ming-Chih
authors: MC
authors: Hou
authors: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Division of Gastroenterology, Department of Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC.
authors: Shou-Dong
authors: SD
authors: Lee
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis; D006501:Hepatic Encephalopathy / Q000209:etiology*; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: bile duct ligation; cyclooxygenase; hepatic encephalopathy; liver cirrhosis; prostacyclin