Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, accelerates gastric ulcer healing in rat.
The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear hormone receptor superfamily that is involved in the control of inflammation and carcinogenesis. We determined the effect of the specific PPAR-gamma ligand, pioglitazone (5-40 mg/kg intragastrically), on the healing of acetic-acid gastric ulcers in rats. At day 8 after ulcer induction, the ulcer area, the gastric blood flow and mucosal expression of proinflammatory cytokines such as interleukin-1beta, tumour necrosis factor alpha (TNF-alpha) and cyclooxygenase-1, cyclooxygenase-2, constitutive nitric oxide synthase (cNOS), inducible nitric oxide synthase (iNOS) and heat shock protein 70 (HSP70) was determined. Pioglitazone reduced the area of gastric ulcers and raised significantly the gastric blood flow at the ulcer margin and downregulated the mRNA for interleukin-1beta, TNF-alpha, cyclooxygenase-2 and iNOS while cyclooxygenase-1 mRNA was not affected. The expression of PPAR-gamma mRNA was increased in the ulcerated gastric mucosa. We conclude that pioglitazone accelerates the healing of preexisting gastric ulcers due to the hyperemia at ulcer margin and the anti-inflammatory action including suppression of interleukin-1beta, TNF-alpha, cyclooxygenase-2 and iNOS and by an overexpression of HSP70.
Konturek
Peter C
PC
First Department of Medicine, University Erlangen-Nuernberg, Erlangen, Germany.
Brzozowski
Tomasz
T
Kania
Joanna
J
Konturek
Stanislaw J
SJ
Kwiecien
Slawomir
S
Pajdo
Robert
R
Hahn
Eckhart G
EG
D000818:Animals; D008024:Ligands; D008297:Male; D000077205:Pioglitazone; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045162:Thiazolidinediones / Q000378:metabolism* / Q000627:therapeutic use*; D014157:Transcription Factors / Q000378:metabolism*
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D011451:Prostaglandin-Endoperoxide Synthases; D000077205:Pioglitazone