Exploiting the role of various types of ion-channels against chemically induced inflammatory bowel disease in male Wistar rats

doi:10.1016/S2222-1808(15)60992-6

Asian Pacific Journal of Tropical Disease

Volume 6, Issue 2, February 2016, Pages 90-99

https://doi.org/10.1016/S2222-1808(15)60992-6 Get rights and content

Abstract

Objective

To evaluate the role of nifedipine (L-type of calcium channel blocker), glibenclamide [cystic fibrosis transmembrane conductance regulator (CFTR) channel blocker], niflumic acid (chloride channels blocker) and 2-aminoethyldiphenyl borate (calcium release-activated channels channel blocker) against chemically induced inflammatory bowel disease in male Wistar rats.

Methods

Inflammatory bowel disease was induced by the administration of 2,4-dinitrobenzene sulfonic acid intracolonically. Animals were divided into 7 groups by keeping 6 animals in each group. Group one and two were treated as normal control and disease control, respectively and seven pretreated with sulfasalazine and remaining groups were treated with test drugs. Animals were pretreated for 5 days before administration of 2,4-dinitrobenzene sulfonic acid. Various parameters were recorded during and after treatment period like disease activity index (body weight, food intake, diarrhea score, occult blood score), biomarkers study in peritoneal macrophages and histopathology of colon.

Results

Glibenclamide had offered significant protective effect on disease activity index, biochemical parameters confirmed by histopathological examination. 2-Aminoethyldiphenyl borate and niflumic acid had also shown insignificant protection in few parameters.

Conclusions

Protection observed by pretreatment of glibenclamide is may be of its blocking effect of CFTR channels of the mast cells, which regulate chloride influx and efflux phenomenon.

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Cited by (1)

Defining the role of CFTR channel blocker and ClC-2 activator in DNBS induced gastrointestinal inflammation
2021, Saudi Pharmaceutical Journal
Citation Excerpt :
In the present study, DNBS induced colitis caused up-regulation of DAI (decline in food intake, loss of body weight, an increase in occult blood in the feces, diarrhea) and an increase in the ulcerative areas, wet weight of colon and spleen compared to the sham group. Glibenclamide has ameliorated the DNBS induced DAI changes and many of the parameters considered in the present experiment (Chidrawar, 2016). Lubiprostone also offered considerable protection concerning the DAI but the effects were not as good as glibenclamide.
In the present study, we have investigated and/or compared the role of glibenclamide, G as cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor, and lubiprostone, L as chloride channel-2 (ClC-2) activator in the 2,4-dinitrobenzene sulfonic acid (DNBS)-induced gastrointestinal inflammation. GI inflammation was induced by intrarectal administration of DNBS. Rats were randomly allocated in 5 groups as sham control, distilled water + DNBS, sulfasalazine (S) + DNBS, G + DNBS, and L + DNBS. All the groups were pre-treated successively for five days before the induction of colitis. One day before and the first four days after DNBS administration various parameters were studied. Later, blood chemistry, colon’s gross structure, histology, and the antioxidant load was examined. Pre-treatment with G significantly protected the change induced by DNBS concerning the change in body weight, food intake, diarrhea, occult blood in the feces, wet weight of the colon, and spleen. G because of its anti-inflammatory property down-regulated the neutrophil and WBC count and up-regulated the lymphocyte number. Moreover, G efficiently ameliorates the oxidative stress in the colon and declines the level of myeloperoxidase and malondialdehyde and up-regulated the level of superoxide dismutase and glutathione. Lubiprostone has not shown any promising effects, in fact, it causes an increase in diarrheal frequency. Our findings from this study represent that G has good potential to ameliorate GI inflammation induced by DNBS by its multiple actions including CFTR blockage and reducing the release of inflammatory markers from the MCs, anti-inflammatory and free radical scavenging property.

Available online 22 Jan 2016

All experimental procedures involving animals were conducted in accordance to Nations Animal Ethical Guidelines and approved by Institutional Animal Ethical Committee and Committee for the Purpose of Control and Supervision on Experiments on Animals.

The journal implements double-blind peer review practiced by specially invited international editorial board members.

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Original articleExploiting the role of various types of ion-channels against chemically induced inflammatory bowel disease in male Wistar rats

Abstract

Objective

Methods

Results

Conclusions

Immunol Lett

Transl Res

Biochim Biophys Acta

Eur J Pharmacol

Int J Pharm

Eur J Pharm Biopharm

J Ethnopharmacol

Neurosci Lett

Int Immunopharmacol

Acta Histochem

Exp Mol Pathol

Pharmacol Ther

Gastroenterol Clin Biol

Clinics (Sao Paulo)

Mutat Res

Analysis of colonic mucosa mast cell count in patients with chronic diarrhea

Saudi J Gastroenterol

Neuro inflammation in inflammatory bowel disease

J Neuroinflammation

The role of TRP proteins in mast cells

Front Immunol

Calcium release-activated calcium current in rat mast cells

J Physiol

Calcium signaling in mast cells: focusing on L-type calcium channels

Adv Exp Med Biol

Mast cell ion channels

Chem Immunol Allergy

Calcium channel blockers and modulation of innate immunity

Curr Opin Infect Dis

Identification of ClC-2 and CIC-K2 chloride channels in cultured rat type IV spiral ligamentfibrocytes

J Assoc Res Otolaryngol

Differential contribution of TM6 and TM12 to the pore of CFTR identified by three sulfonylurea-based blockers

Pflugers Arch

Antidiabetic and hypolipidemic effects of Dorema aucheri hydroalcoholic leave extract in streptozotocin-nicotinamide induced type 2 diabetes in male rats

Iran J Basic Med Sci

Brain damage from soman-induced seizures is greatly exacerbated by dimethyl sulfoxide (DMSO): modest neuroprotection by 2-aminoethyl diphenylborinate (2-APB), a transient receptor potential channel inhibitor and inositol 1,4,5-triphosphate receptor antagonist

J Med CBR Def

Original article
Exploiting the role of various types of ion-channels against chemically induced inflammatory bowel disease in male Wistar rats