title: Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone.
abstract: Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX) has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p.) as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M), and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001). NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001). GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05). Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05). MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sarhadi Kholari
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. AND Metabolic Disorders Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mitra
authors.initials: M
authors.lastname: Nourbakhsh
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Doustimotlagh
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Molood
authors.initials: M
authors.lastname: Bagherieh
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Golestani
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D054407:Chemokine CCL4 / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009271:Naltrexone / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: C066507:CCL4 protein, human; D054407:Chemokine CCL4; D008315:Malondialdehyde; D009271:Naltrexone; D002251:Carbon Tetrachloride
keywords: Carbon tetrachloride; Cirrhosis; Naltrexone; Oxidative stress