Mahsa Ale-Ebrahim1, Akram Eidi1, Pejman Mortazavi2, Seyyed Mohammad Tavangar3, Darioush Minai Tehrani4. 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. Electronic address: sp.mortazavi@srbiau.ac.ir. 3. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Biology, Shahid Beheshti University, Tehran, Iran.
Abstract
PROJECT: Cholestasis 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. PROCEDURE: After BDL, rats were given sodium molybdate (0.05 or 0.1 or 0.2g/kg) or urosodeoxycholic acid (UDCA, 25mg/kg) via intragastric gavage for 45 consecutive days (once per day). RESULTS: BDL 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. CONCLUSIONS: The 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.
PROJECT: Cholestasis 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. PROCEDURE: After BDL, rats were given sodium molybdate (0.05 or 0.1 or 0.2g/kg) or urosodeoxycholic acid (UDCA, 25mg/kg) via intragastric gavage for 45 consecutive days (once per day). RESULTS: BDL 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. CONCLUSIONS: The 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.
Authors: Eman E Shaban; Dina M Salama; Mahmoud E Abd El-Aziz; Khadiga S Ibrahim; Soad M Nasr; Hassan M Desouky; Hagar F H Elbakry Journal: Sci Rep Date: 2022-07-15 Impact factor: 4.996