Pathways involved in mild gastrointestinal inflammation induced by a low level exposure to a food contaminant.
Chronic gut inflammation is associated with radical oxygen species (ROS) genesis. ROS may activate certain transcription factors such as nuclear factor kappa beta (NF-kappaB), which regulates cyclooxygenase-2 (COX-2). Diquat, a food contaminant, is responsible for oxidative stress. This work aimed to establish the involvement of ROS and prostanoids on diquat-induced gastrointestinal inflammation and mast cell hyperplasia. Diquat increased gastrointestinal MPO activity and mast cell number. Its effect on gastric MPO activity was reversed by PD 138,387 (a COX-2 selective inhibitor) and PDTC (an inhibitor of NF-kappaB activation) but not by DMSO (a hydroxyl radical scavenger) and allopurinol (a xanthine oxidase inhibitor). In contrast, increased jejunal MPO activity was blocked by both DMSO, PD 138,387, and PDTC, while allopurinol enhanced it. PD 138,387 and PDTC reduced gastrointestinal mast cell number while DMSO and allopurinol did not Diquat-induced inflammation involves a gastrointestinal NF-kappaB activation and COX-2 dependent proinflammatory prostanoid synthesis. Furthermore, the hydroxyl radical is involved in intestinal but not gastric inflammation.
Anton
Pauline M
PM
INRA, Neuro-Gastroenterology and Nutrition Unit, Toulouse, France.
Theodorou
Vassilia
V
Roy
Sabine
S
Fioramonti
Jean
J
Bueno
Lionel
L
D000818:Animals; D003092:Colitis / Q000503:physiopathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004178:Diquat / Q000009:adverse effects; D005506:Food Contamination; D005756:Gastritis / Q000503:physiopathology*; D006540:Herbicides / Q000009:adverse effects; D006965:Hyperplasia; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006540:Herbicides; D007527:Isoenzymes; D016328:NF-kappa B; C108957:PD 138387; D010636:Phenols; D011759:Pyrrolidines; D013844:Thiazoles; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D004178:Diquat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases