title: Comparison of antioxidative and antifibrotic effects of α-tocopherol with those of tocotrienol-rich fraction in a rat model of chronic pancreatitis.
abstract: OBJECTIVE
  The α-tocopherol and tocotrienol-rich fraction (TRF) are considered effective antioxidants. This study aimed to compare the antioxidative and antifibrotic effects of α-tocopherol and TFR in dibutylin dichloride (DBTC)-induced chronic pancreatitis (CP) rats.
  
  
  METHODS
  Oral administration of α-tocopherol and TFR (both 800 mg/kg per day) started the next day after DBTC (8 mg/kg) infusion into the tail vein for 4 weeks. Histological examination, Sirius red staining, and measurement of the contents of hydroxyproline and malondialdehyde of the pancreas were performed to evaluate pancreatic damage and fibrosis. Immunohistochemical analysis of α-smooth muscle actin and real-time reverse transcription polymerase chain reaction for transforming growth factor-β1 (TGF-β1) and collagen-α1(I) were performed to evaluate the activation of pancreatic stellate cells and the mRNA levels of fibrosis-related genes, respectively.
  
  
  RESULTS
  Both α-tocopherol and TRF reduced oxidative stress, ameliorated inflammation and fibrosis, and down-regulated the mRNA expression of TGF-β1 and collagen-α1(I) in DBTC-induced CP. The TRF was superior to α-tocopherol in alleviating inflammation and fibrosis and down-regulating TGF-β1 mRNA expression.
  
  
  CONCLUSIONS
  Oral administration of α-tocopherol and TRF improves pancreatic inflammation and fibrosis in DBTC-induced CP rats, with TRF being more effective than α-tocopherol. Therefore, TRF may be a novel option for alleviating inflammation and, particularly, the fibrotic process in CP.
authors.affiliation: Department of Gastroenterology, Affiliated Changhai Hospital, 2nd Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Jiang
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Liao
authors.forename: Liang-Hao
authors.initials: LH
authors.lastname: Hu
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Du
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Man
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Gong
authors.forename: Zhao-Shen
authors.initials: ZS
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009947:Organotin Compounds; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D024508:Tocotrienols / Q000008:administration & dosage / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000199:Actins; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D006909:Hydroxyproline; D008315:Malondialdehyde; D009947:Organotin Compounds; D012333:RNA, Messenger; D024508:Tocotrienols; D053773:Transforming Growth Factor beta1; D024502:alpha-Tocopherol; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat; C020735:dibutyldichlorotin