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INFLAMMATION/IMMUNITY/MEDIATORS

Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis

¹Digestive System Research Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, 08035 Barcelona; and ²Hospital Mutua, 08221 Terrassa, Spain

Submitted 4 August 2003 ; accepted in final form 1 March 2004

The objective was to investigate the effects of vitamin E on collagen deposition induced by Cyclosporin A (CsA) administration in rats with caerulein (Cr) pancreatitis. CsA transforms the fully regenerative, self-limited form of Cr pancreatitis into a chroniclike disease in conjunction with increased transforming growth factor (TGF)- and myofibroblast proliferation. Vitamin E inhibits TGF- release in mesangial cells and reduces CsA cytotoxicity. Wistar rats received CsA daily (20 mg/kg), and CR pancreatitis was induced on days 1 and 8 (Cr + CsA group). In a separate group, vitamin E (600 mg·kg^–1·day^–1) was administered starting 4 days before CsA. Three other groups received either vehicle, CsA, or Cr alone. Thiobarbituric acid-reactive substance (TBARS), 8-isoprostanes, and hyaluronic acid were measured in plasma obtained on the day the animals were killed (day 15). Pancreases were weighed and processed for light microscopy to assess connective tissue and myofibroblast number. Pancreatic homogenates were also assayed for collagen (hydroxyproline) and TBARS content. TBARS, 8-isoprostane, and TGF- were elevated in CsA and Cr + CsA rats. Vitamin E treatment greatly decreased these parameters. Vitamin E also decreased the fall in pancreatic weight observed in Cr + CsA pancreas. Pancreatic hydroxyproline and plasma hyaluronic acid were increased in Cr + CsA rats but were effectively reduced by vitamin E. Morphology showed improvement in fibrosis score and a decreased number of myofibroblasts in vitamin E-treated rats. Vitamin E reduces oxidative stress and collagen deposition during the development of experimental chronic pancreatitis. Adjuvant antioxidants may be of value in the treatment of chronic pancreatitis.

cyclosporin; caerulein; myofibroblasts; fibrogenesis