Z Gastroenterol 2014; 52 - A33
DOI: 10.1055/s-0034-1376093

Effects of hydrogen sulphide on heme oxigenase activity in TNBS induced colitis

K Kupai 1, Z Szalai 1, M Korsós 1, Z Baráth 2, S Török 1, R Szabó 1, A Csonka 1, L Daruka 1, A Pósa 1, C Varga 1
  • 1Dept. of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
  • 2University of Szeged, Faculty of Dentistry and Department of Orthodontics and Pediatric Dentistry, Szeged, 6720, Hungary

Hydrogen sulfide (H2S) is an endogenous mediator that relaxes vascular smooth muscle, exhibits several antiinflammatory activities and contributes to protection. Specially, we investigated the beneficial effects of H2S and whether heme-oxigenases (HO) are involved in the H2S-induced colonal cytoprotection against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.

Male Wistar rats were treated with TNBS (10 mg) to induce colitis. H2S donor (Lawesson's reagent) were used at different concentrations (60; 30; 15; 7.5; 3.75; 1.87;0.93µM; dissolved in carboxymethylcellulose twice daily per os (from 0 day to 3. day). 72h after TNBS treatment colon samples were collected to measure extent of inflammation, myeloperoxidase (MPO), and HO activities and TNF-α content.

In a separate experiment, HO activity was inhibited by tin protoporphyrin (SnPP, 30 micromol/kg/day, s.c) at the day of TNBS challenge (10 mg) co-treatment with H2S donor (2 × 1.87µM, per os).

Twice-daily treatment with H2S donors significantly decreased the extent of colonal inflammation in a dose dependent manner compared to vehicle-treatment. The most effective concentration was 2 × 1.87µM at the extent of inflammation (27.4 ± 1.5 vs. 46.2 ± 4.3; %). Per os administration of H2S donor reduced TNBS-provoked MPO activity (19.07 ± 3.6 vs. 42. 98 ± 10; mU/mg/protein), TNF-α levels (89.95 ± 9.43 vs. 531.67 ± 32; pg/mg protein) while increasing colonic HO enzyme activity (0.98 ± 0.05 vs. 0.82 ± 0.6 nmol bilirubin/h/mg protein).

The protective effect of H2S was abolished by co-treatment with an inhibitor of HO activity (TNBS: 35.6 ± 2.4; TNBS+H2S: 21.6 ± 5.6; TNBS+H2S+SnPP: 28.8 ± 2.6% extent of lesion) (from 60.6 ± 15.7 to 80.89 ± 7.3% of the extension of TNBS lesion)

Our findings suggest that H2S confers protection dose dependently, probably by modulation of anti-inflammatory parameters and HO enzyme activity. Our results support the proposal that induction of HO activity by H2S provides a protective mechanism in this model.

This research was realized in the frames of TÁMOP 4.2.4. A/2 – 11 – 1-2012 – 0001 National Excellence Program – Elaborating and operating an inland student and researcher personal support system. The project was subsidized by the European Union and co-financed by the European Social Fund.