title: A role of 1,25(OH)2D3 supplementation in rats with nonalcoholic steatohepatitis induced by choline-deficient diet.
abstract: OBJECTIVE
  It has been reported that 1,25(OH)2D3 (1,25-VD3) ameliorates the progression of nonalcoholic steatohepatitis (NASH). However, it is unclear whether 1,25-VD3 plays a role in NASH induced by a choline-deficient (CD) diet. In this study, we investigated the roles of 1,25-VD3 in the development and progression of NASH in rats induced by a CD diet.
  
  
  RESULTS
  Wistar rats with NASH induced by a CD diet were subjected to intraperitoneal injections of 1, 5, or 10 μg/kg of 1,25-VD3 twice weekly for 12 weeks. The administration of 1,25-VD3 decreased free fatty acids (FFAs), triglycerides (TGs), thiobarbituric acid-reactive substances (TBARS), the number of apoptotic cells, and the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the liver, and it improved liver histology, but it did not change the total antioxidant capacity (TAOC) in the liver. Interestingly, the level of CK18-M30 was decreased in the liver of model animals. Treatment with 1,25-VD3 may restrain the downregulation of CK18-M30 in the liver and its release into the bloodstream, thus decreasing the level of serum CK18-M30. 1,25-VD3 supplementation elevated the serum level of 25(OH)D3 and the expression of VDR in the liver. The dose-effect relationship of 1,25-VD3 indicated that 1,25-VD3 slows down the development and progression of NASH induced by a CD diet, but higher doses of 1,25-VD3 may lead to adverse effects.
  
  
  CONCLUSIONS
  The results suggest the presence of both antagonistic and adverse dose-dependent effects of the long-term supplementation of 1,25-VD3 on NASH induced by a CD diet.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji, China.
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.
authors.forename: M
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Laboratory Medicine, Affiliated Hospital of Yanbian University, Yanji, China.
authors.forename: X
authors.initials: X
authors.lastname: You
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji, China.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji, China. Electronic address: xixupiao@aliyun.com.
authors.forename: X
authors.initials: X
authors.lastname: Piao
authors.affiliation: Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China. Electronic address: jinguang1@ybu.edu.cn.
authors.forename: G
authors.initials: G
authors.lastname: Jin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000097:blood / Q000633:toxicity*; D002796:Choline Deficiency / Q000150:complications*; D004032:Diet; D019587:Dietary Supplements / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D017208:Rats, Wistar; D012307:Risk Factors; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008055:Lipids; C576839:TIMP1 protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D019715:Tissue Inhibitor of Metalloproteinase-1; D002117:Calcitriol
keywords: 1,25(OH)(2)D(3); 25-(OH)D(3); Choline; Nonalcoholic steatohepatitis; Vitamin D receptor