Pioglitazone, a Specific PPAR-gamma Ligand, Inhibits Aspirin-induced Gastric Mucosal Injury in Rats

Background: Neutrophils activation and tumour necrosis factor-alpha (TNF-alpha) induction play a critical role in aspirin-induced gastric mucosal injury. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR-gamma ligand, can ameliorate aspirin-induced gastric mucosal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF-alpha expression.

Methods: Aspirin-induced injury was produced by the intragastric administration of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 mL/kg). Pioglitazone was given to the rats by gastric intubation 1 h before the aspirin administration. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The gastric concentration of TNF-alpha and the expression of TNF-alpha mRNA was determined by ELISA and reverse transcriptase-polymerase chain reaction.

Results: The intragastric administration of acidified aspirin induced hyperemia and haemorrhagic erosions in rat stomachs. The increase in the total gastric erosive area after aspirin administration was significantly inhibited by treatment with pioglitazone in a dose-dependent manner. The increases in thiobarbituric acid-reactive substances and myeloperoxidase activity after aspirin administration were both significantly inhibited by pre-treatment with pioglitazone (10 mg/kg). The gastric content of TNF-alpha increased and the expression of TNF-alpha mRNA was up-regulated after aspirin treatment. However, the peak TNF-alpha mRNA expression 1 h after aspirin administration was inhibited by pioglitazone.

Conclusion: Based on these data, the beneficial effects of pioglitazone on aspirin-induced gastric mucosal injury may be attributed to its anti-inflammatory properties.