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Hepatoprotective and antifibrotic effects of sodium molybdate in a rat model of bile duct ligation
Institution:1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran;2. Department of Pathology, Faculty of specialized Veterinary, Science and Research Branch, Islamic Azad University, Tehran, Iran;3. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Biology, Shahid Beheshti University, Tehran, Iran;1. FOODplus Research Centre, School of Agriculture Food and Wine, The University of Adelaide, Adelaide 5064, South Australia, Australia;2. Waite Analytical Service, School of Agriculture Food and Wine, The University of Adelaide, Adelaide 5064, South Australia, Australia;3. Women''s and Children''s Health Research Institute, Women''s and Children''s Hospital, King William Road, North Adelaide 5006, South Australia, Australia;4. Sansom Institute for Health Research, University of South Australia, Adelaide 5001, South Australia, Australia;1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran;2. Department of Pathology, Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran;1. Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran;2. Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran;3. Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;4. Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;5. Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord 34141, Iran;1. Population Health and Optimal Health Practices Research Unit, Research Center of CHU of Quebec, Laval University, Quebec, QC, Canada;2. Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec, QC, Canada;3. National Public Health Institute of Quebec, QC, Canada;1. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran;2. Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran;3. Department of Microbiology and Immunology, Kerman University of Medical Sciences, Kerman, Iran;4. Research Center for Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran;5. Environmental Health Engineering Research Centers, Kerman University of Medical Sciences, Kerman, Iran;1. Murray & Associates, 5529 Perugia Circle, San Jose, CA, 95138, USA;2. Harrington House, Brighton, BN1 6RE, UK;3. SAHCo Ltd, Chester, CH3 7JW, UK;4. Charles River Laboratories, Inc., 905 Sheehy Drive, Horsham, PA, 19044, USA;5. International Molybdenum Association, 325 Avenue Louise, 1050, Brussels, Belgium
Abstract:ProjectCholestasis liver fibrosis has been increasingly recognized as a cause of high morbidity and mortality in humans. The accumulation of toxic bile salts in a bile duct ligation (BDL) animal model plays a pivotal role in the induction of liver fibrosis. Cholestatic liver fibrosis is characterized by excessive collagen production and deposition, which is mediated by reactive oxygen species (ROS). Molybdenum is an essential micronutrient trace element which acts as a cofactor in many detoxification system enzymes. The aim of the present study was to evaluate the antifibrotic effect of sodium molybdate on liver cholestasis induced by bile duct ligation in rats.ProcedureAfter BDL, rats were given sodium molybdate (0.05 or 0.1 or 0.2 g/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) via intragastric gavage for 45 consecutive days (once per day).ResultsBDL drastically increased the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and direct bilirubin, whereas it reduced the levels of antioxidant enzymes, superoxide dismutase and catalase in the liver. Treatment of BDL rats with sodium molybdate significantly attenuated these changes. As determined by Masson's trichrome staining, BDL markedly induced the liver fibrosis. These alterations were also significantly attenuated by sodium molybdate administration.ConclusionsThe results of this study indicate the hepatoprotective and antifibrotic effect of sodium molybdate in the cholestatic liver. Sodium molybdate, by inhibiting the activation of Ito cells, decreases the collagen production in the liver. The antifibrotic effect of sodium molybdate is likely due to the antioxidative and free radical scavenging effects of this trace element.
Keywords:Bile duct ligation (BDL)  Cholestasis  Liver fibrosis  Rat  Sodium molybdate
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