Recent Advances in Patient Treatment and Care (Track)




The effect of pioglitazone, a specific ligand of the proxisome prolifrator-activated receptor gamma, on ethanol-induced gastric ulcers in cirrhotic rats: the role of nitric oxide and IL1-ß

Leila Moezi
Assistant Professor of Pharmacology School of Medicine Shiraz University of Medical Sciences Shiraz, Iran

Abstract:

The frequency of gastrointestinal ulcerations is high in cirrhotic patients. Recently, it has been shown that pioglitazone exhibits gastroprotective actions. This study designed to investigate effect of pioglitazone, on the mucosal lesions in cirrhotic rats.

Different groups of bile duct-ligated and sham animals received saline, or 5, 10 or 15 mg/kg pioglitazone, for 5 days in the last days of 28-day period of cirrhosis. On day 28, rats were killed 1 hour after oral ethanol administration and the area of gastric lesions was measured. The serum of rats also collected to evaluate serum concentrations of TNF-α and IL1-β.

Pretreatment with pioglitazone dose dependently attenuated gastric lesions induced by ethanol in both sham and cirrhotic rats, but this effect was more significant in cirrhotic ones. L-NAME, a non selective inhibitor of nitric oxide synthase (NOS), decreased pioglitazone-induced gastric healing effect in cirrhotic rats, while aminoguanidine, a selective inducible NOS inhibitor, increased pioglitazone-induced gastric healing effect in the same group. The protective effect of pioglitazone was accompanied by a fall in serum IL1-β level.

In conclusion chronic treatment with pioglitazone exerts a potent gastroprotective effect on the stomach ulcers of cirrhotic rats probably due to constitutive NOS induction or inhibition of IL1-β level production.