Nitric Oxide Mediates Effects of Acute, not Chronic Naltrexone on LPS-Induced Hepatic Encephalopathy in Cirrhotic Rats

Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptors antagonist, and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals treated with saline; naltrexone (10 mg/kg, i.p.); L-NAME (3 mg/kg, i.p.); alone or in combination by naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected one hour after the final drug treatment. Hepatic encephalopathy scoring, hepatic histology and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute- and chronic treatment with naltrexone in cirrhotic rats. While, acute- and chronic administration of L-NAME did not change hepatic encephalopathy scores in cirrhotic rats. The effects of acute- but not chronic treatment of naltrexone on hepatic encephalopathy parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute- and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute, and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author