title: Nitric oxide mediates effects of acute, not chronic, naltrexone on LPS-induced hepatic encephalopathy in cirrhotic rats.
abstract: 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 receptor 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 were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE 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. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOxconcentrations 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.
authors.affiliation: a Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.|b Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
authors.forename: Bentolhoda
authors.initials: B
authors.lastname: Ghiassy
authors.affiliation: a Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.|c Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Rahimi
authors.affiliation: c Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
authors.forename: Mehrak
authors.initials: M
authors.lastname: Javadi-Paydar
authors.affiliation: a Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.|c Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
authors.forename: Mohammad Hadi
authors.initials: MH
authors.lastname: Gharedaghi
authors.affiliation: b Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Norouzi-Javidan
authors.affiliation: a Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran 1417613151, Iran.|c Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D004347:Drug Interactions; D006501:Hepatic Encephalopathy / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008070:Lipopolysaccharides; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009271:Naltrexone / Q000008:administration & dosage* / Q000627:therapeutic use*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D051381:Rats
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D009271:Naltrexone; D019331:NG-Nitroarginine Methyl Ester
keywords: acute; aigu; chronic; chronique; cirrhose; cirrhosis; encéphalopathie hépatique; hepatic encephalopathy; naltrexone; nitric oxide; opioids; opioïdes; oxyde nitrique; rats