Sulphur dioxide ameliorates colitis related pathophysiology and inflammation

Abstract

Colitis is an inflammatory disease of the gastrointestinal tract. Inflammation, oxidative stress and cell death constitute the backbone of colitis. Most of the drugs prescribed for inflammatory bowel disease (IBD) have various side effects. In this scenario, we would like to determine the therapeutic role sulphur dioxide, a gaso-transmitter produced through the metabolism of cysteine in colitis. Colitis was induced through intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in male Wistar rats. Rats were administered with 0.9% saline containing Na₂SO₃ and NaHSO₃ (3:1 ratio; i.e., 0.54 mmol/kg and 0.18 mmol/kg body weight) orally 1 h after colitis induction followed by the administration of the same solution after each 12 h for 72 h. TNBS administration resulted in increased oxidative stress, NF-ĸ B and inflammasome activation, ER stress and autophagy. Moreover, TNBS administration also resulted in activation of p53 and apoptosis. SO₂ reversed all these alterations and ameliorated colitis in rats. Administration of an inhibitor of endogenous SO₂ production along with TNBS exacerbated colitis. Results suggest that down-regulation of SO₂ / glutamate oxaloacetate transaminase pathway is involved in IBD. The protective role of SO₂ in colitis is attributed to its anti-inflammatory and anti-oxidant nature. Down-regulation of SO₂/glutamate oxaloacetate transaminase pathway is involved in IBD. Since SO₂ is not toxic at low concentration and endogenously produced, it may be used with prescribed drugs for synergistic effect after intensive research. Our result demonstrated the therapeutic role of SO₂ in colitis for the first time.

Keywords: Apoptosis; Autophagy; ER stress; Inflammation; Oxidative stress; Sulphur dioxide.