학술논문
The influence of TRAIL, adiponectin and sclerostin alterations on bone loss in BDL-induced cirrhotic rats and the effect of opioid system blockade.
Document Type
Academic Journal
Author
Moradi M; Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Doustimotlagh AH; Department of Clinical Biochemistry, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.; Dehpour AR; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Rahimi N; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.; Golestani A; Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Occupational Sleep Research Center (OSRC), Tehran University of Medical Sciences, Bahrloo Hospital, Tehran, Iran. Electronic address: golsetan@tums.ac.ir.
Source
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
Subject
Language
English
Abstract
Aims: Osteoporosis is a common extra-hepatic complication in patients with chronic liver disease. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), sex hormones, adiponectin, and sclerostin are involved in the regulation of bone turnover but little is known about their role in the promotion of hepatic osteodystrophy. Endogenous opioids are reported to increase during cholestasis and may influence bone resorption. The purpose of this study was to investigate the circulating levels of these factors and their expression in the femur of bile duct ligated (BDL) rats, to evaluate the biomechanical bone strength, and the effect of naltrexone (NTX).
Materials and Methods: BDL and sham-operated (SO) rats received 10 mg/kg NTX as an opioid-receptors antagonist or saline once daily for 28 days intraperitoneally. Three-point bending test was performed on the right femurs and, plasma bone alkaline phosphatase (BALP), sex hormones, TRAIL, adiponectin, sclerostin, as well as the mRNA expression levels of the latter three proteins, were measured in the femur tissues.
Key Findings: Plasma TRAIL, estrogen, adiponectin, sclerostin and, BALP levels increased in BDL animals when compared to the related controls, whereas testosterone level decreased and NTX reversed these effects significantly. Femur strength decreased in cirrhotic animals and interestingly, blocking opioid-receptors by NTX improved it significantly (p ≤ 0.05).
Significance: High levels of TRAIL, adiponectin and, sclerostin after bile duct ligation, suggest that these factors may have some roles in bone loss after cirrhosis. Administration of NTX improved all the mentioned factors except for bone strength. Effect of NTX on bone loss in BDL rats needs more study to clarify.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Materials and Methods: BDL and sham-operated (SO) rats received 10 mg/kg NTX as an opioid-receptors antagonist or saline once daily for 28 days intraperitoneally. Three-point bending test was performed on the right femurs and, plasma bone alkaline phosphatase (BALP), sex hormones, TRAIL, adiponectin, sclerostin, as well as the mRNA expression levels of the latter three proteins, were measured in the femur tissues.
Key Findings: Plasma TRAIL, estrogen, adiponectin, sclerostin and, BALP levels increased in BDL animals when compared to the related controls, whereas testosterone level decreased and NTX reversed these effects significantly. Femur strength decreased in cirrhotic animals and interestingly, blocking opioid-receptors by NTX improved it significantly (p ≤ 0.05).
Significance: High levels of TRAIL, adiponectin and, sclerostin after bile duct ligation, suggest that these factors may have some roles in bone loss after cirrhosis. Administration of NTX improved all the mentioned factors except for bone strength. Effect of NTX on bone loss in BDL rats needs more study to clarify.
(Copyright © 2019 Elsevier Inc. All rights reserved.)