Z Gastroenterol 2006; 44 - A45
DOI: 10.1055/s-2006-943412

5-amino salicylic acid induced depletion of glutathione protects the colon against trinitrobenzene sulphonic acid injury through heme oxygenase-1 enzyme expression

K Horváth 1, F László 2, B Whittle Jr 3, A Pósa 1, A Molnár 1, A Berkó 1, C Varga 1
  • 1Department of Comparative Physiology, University of Szeged, Szeged, Hungary
  • 2Institute of Physical Education of Sport Sciencies, University of Szeged, Szeged, Hungary
  • 3The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK

Introduction: 5-amino salicylic acid (5-ASA) is successfully used in the treatment of inflammatory bowel disease (IBD). The better understanding of the mechanism of action of 5-ASA may lead further insight to the etiology of IBD. We know that oxidative stress plays a key role in causing inflammation. Thus, antioxidant enzyme systems have an important defensive function. The induction of the antioxidant systems, heme oxygenase-1 (HO-1) enzyme and glutathione (GSH) are involved in the maintenance of intestinal mucosal integrity.

Aim: We examined the effect of the 5-ASA-provoked GSH depletion for the role of HO-1 induction in experimental colitis in different times.

Methods: We administered 2,4,6-trinitrobenzene sulphonic acid (TNBS; 10mg; i.c.) to male Wistar rats to initiate colonic inflammation. Animals were pre-treated with 5-ASA (75mg/kg, i.c.) 24 hours before and 3 hours after TNBS treatment. The extent of the lesions (assessed by planimetry), total GSH content and HO enzyme activity and expression (Western blot) were measured from the colon.

Results: We found that 5-ASA reduced TNBS-provoked colonic inflammation and increased HO-1 enzyme activity through the expression of HO-1. This effect of 5-ASA is mediated by GSH depletion.

Conclusions: Activation of the HO-1 enzyme protects the colon against inflammation. GSH depletion plays role in this activation. Induction of HO-1 through the depletion of GSH content, at least in part, is involved in the anti-inflammatory action of 5-ASA.

Acknowledgements: The present work was supported by the Hungarian Ministry of Economy and Transport (GVOP-3.2.1.-2004–04–0086/3.0