Lack of detrimental or therapeutic effects of cyclooxygenase inhibition in bile duct-ligated rats with hepatic encephalopathy

Background: The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Cerebral blood flow regulated by cyclooxygenase (COX) may be involved in the development of HE. There are no comprehensive data concerning the effects of COX inhibition on HE in chronic liver disease. Methods: Male Sprague-Dawley rats weighing 240-270 g at the time of surgery were selected for experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Those rats were then divided into two groups to receive i.p. injection of indomethacin (5 mg/kg per day) or distilled water for 7 days from day 36 to day 42 after BDL. The control group consisted of rats receiving a sham operation. Severity of encephalopathy was assessed by counts of motor activity. Plasma levels of tumor necrosis factor (TNF)-alpha and 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha)), and liver biochemistry tests were determined after treatment. Results: The motor activity in both groups of BDL rats were significantly lower than that of the control group (P < 0.001). As compared with the BDL rats treated with distilled water, BDL rats treated with indomethacin had significant lower levels of 6-keto-PGF(1 alpha), but the motor activity, TNF-alpha levels and serum biochemistry tests were not significantly different between both BDL groups. Conclusions: Chronic indomethacin administration did not have significantly detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.