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 101
- Downloads 0
Effect of indometacin pretreatment on protamine sulfate-mediated relaxation of the isolated rat uterus: the role of the antioxidative defense system.
Previous results in this laboratory indicate that protamine sulfate (PS) evokes dose-dependent relaxation of both spontaneous and calcium ion-induced uterus activity mediated predominantly by potassium channels and, to a...
Physiology and pharmacological role of the blood-brain barrier.
The central nervous system (CNS) is a perfectly regulated environment with conditions far different from those in the rest of the organism. Even slight changes in this machinery affect its functioning. The blood-brain ba...
Imipramine counteracts corticosterone-induced enhancement of glutamatergic transmission and impairment of long-term potentiation in the rat frontal cortex.
The effects of corticosterone administration lasting for 7 and 21 days were studied ex vivo in rat frontal cortex slices prepared 48 h after the last dose of the hormone. In slices originating from corticosterone-treated...
Impact of hypercholesterolemia on toxicity of N-nitrosodiethylamine: biochemical and histopathological effects.
N-nitrosodiethylamine (NDEA) is an important carcinogen frequently present in human environment and food chain. Nitrosamines such as NDEA produce oxidative stress due to generation of reactive oxygen species and alter th...
Regulation of serotonin N-acetyltransferase activity in the chick pineal gland by UV-A and white light: role of MK-801- and SCH 23390-sensitive retinal signals.
The rhythmic melatonin synthesis in the pineal gland is one of the most extensively studied circadian rhythms in vertebrates. Light is the dominant environmental factor controlling this process. Light at night acutely su...