Comparison of antioxidative and antifibrotic effects of α-tocopherol with those of tocotrienol-rich fraction in a rat model of chronic pancreatitis

Pancreas. 2011 Oct;40(7):1091-6. doi: 10.1097/MPA.0b013e31821b59c6.

Abstract

Objectives: 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.

Publication types

  • Comparative Study

MeSH terms

  • Actins / metabolism
  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Disease Models, Animal
  • Fibrosis
  • Gene Expression Regulation / drug effects
  • Hydroxyproline / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Organotin Compounds
  • Oxidative Stress / drug effects
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatitis, Chronic / chemically induced
  • Pancreatitis, Chronic / drug therapy*
  • Pancreatitis, Chronic / genetics
  • Pancreatitis, Chronic / metabolism
  • Pancreatitis, Chronic / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors
  • Tocotrienols / administration & dosage
  • Tocotrienols / pharmacology*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / pharmacology*

Substances

  • Actins
  • Anti-Inflammatory Agents
  • Antioxidants
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Organotin Compounds
  • RNA, Messenger
  • Tgfb1 protein, rat
  • Tocotrienols
  • Transforming Growth Factor beta1
  • smooth muscle actin, rat
  • Malondialdehyde
  • alpha-Tocopherol
  • dibutyldichlorotin
  • Hydroxyproline