Enhanced anti-ulcer effect of pioglitazone on gastric ulcers in cirrhotic rats: The role of nitric oxide and IL-1β.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 1
Abstract
Background: The frequency of gastrointestinal ulcerations is higher in cirrhotic patients than in the normal population. It has been shown that pioglitazone exhibits gastroprotective actions. This study was designed to investigate the effect of pioglitazone, on the gastric mucosal lesions in cirrhotic rats. Methods: Different groups of bile duct-ligated and sham animals received solvent, 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 h after oral ethanol administration and the area of gastric lesions was measured. The serum of rats was also collected to evaluate serum concentrations of TNF-α and IL-1β. Histopathologic examination of liver specimens was also done with hematoxylin-eosin to show possible toxicity of pioglitazone in cirrhosis. Results: Pretreatment with pioglitazone dose dependently attenuated gastric lesions induced by ethanol in both sham and cirrhotic rats, but this effect was more prominent in cirrhotic ones. L-NAME, a non-selective inhibitor of nitric oxide synthase, decreased pioglitazone-induced gastric healing effect in cirrhotic rats, while aminoguanidine, a selective inducible nitric oxide synthase inhibitor, increased pioglitazone-induced gastric healing effect in the same group. The protective effect of pioglitazone was accompanied by a fall in serum IL-1β level. Conclusions: Chronic treatment with pioglitazone exerts a more prominent gastroprotective effect on the stomach ulcers of cirrhotic rats compared to control group probably due to constitutive nitric oxide synthase induction or inducible nitric oxide synthase inhibition. Suppression of IL-1β could be another mechanism in pioglitazone-induced healing effect of gastric ulcers in cirrhotic rats.
Authors and Affiliations
Leila Moezi, Reza Heidari, Zahra Amirghofran, Ali Nekooeian, Ahmad Monabati
Keywords
Related Articles
- EP ID EP135734
- DOI -
- Views 100
- Downloads 0
Involvement of adenosine receptor agonists on the development of hypersensitivity to acute dose of morphine during morphine withdrawal period.
In the present study, the involvement of the selective adenosine A(1) (CPA) and A(2A) (CGS 21680) and non-selective adenosine A(1)/A(2A) (NECA) receptor agonists on the development of hypersensitivity to acute morphine i...
C3435T polymorphism of the ABCB1 gene: impact on genetic susceptibility to peptic ulcers.
The functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the ABCB1 gene encoding the xenobiotic transporter P-glycoprotein (P-gp) may influence susceptibility to several diseases, as well as the clinical...
Neuronal autophagy in cerebral ischemia - a potential target for neuroprotective strategies?
Although many attempts have been made, stroke treatment options are still extremely limited and brain ischemia remains the leading cause of death and disability worldwide. Two major strategies for ischemic stroke, reperf...
Anti-hypertensive effects of probenecid via inhibition of the α-adrenergic receptor.
Probenecid has long been used in the treatment of gout. Its anti-gout mechanisms consist of uric acid reuptake inhibition and the consequent facilitation of uric acid excretion. In the present study, we investigated whet...
Lack of effect of some dopamine and non-dopamine receptor ligands on amphetamine-induced changes in the rat brain neuropeptide Y system.
None of the receptor ligands studied: the dopamine D(2) antagonist eticlopride, D(2)/D(3) antagonist haloperidol, alpha(1)-adrenergic antagonist prazosin, N-methyl-D-aspartate antagonist MK-801, 5-HT(2)/D(2) antagonist m...