{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:44:05Z","timestamp":1791089045258,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T00:00:00Z","timestamp":1390867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\n<jats:list>\n\n<jats:list-item><jats:p>Irritable bowel syndrome (<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>) is a prevalent disease characterized by abdominal pain and abnormal bowel habits. Pioglitazone is a peroxisome proliferator\u2010activated receptor (<jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>) <jats:italic>\u03b3<\/jats:italic> agonist and, although it is mostly used as an antidiabetic agent, it has been reported to have analgesic effects. Nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>), a gaseous molecule that mediates many of the effects of pioglitazone, has been implicated in the pathophysiology of <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>. The aim of the present study was to investigate the effects of pioglitazone on symptoms in a rat model of diarrhoea\u2010predominant <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> (D\u2010<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>).and to determine the role of NO in these effects.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Diarrhoea\u2010predominant IBS was induced by intracolonic instillation of acetic acid. Pioglitazone (2\u00a0mg\/kg, i.p.) was administered on Days 7, 9 and 11 after acetic acid instillation. To investigate the mechanism involved in pioglitazone action, rats were also administered either the PPAR\u03b3 antagonist GW9662 (3\u00a0mg\/kg, i.p.), the NO synthase (NOS) inhibitor <jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>l\u2010<\/jats:sc>arginine methyl ester (<jats:sc>l<\/jats:sc>\u2010NAME; 10\u00a0mg\/kg, i.p.) or the NO precursor <jats:sc>l<\/jats:sc>\u2010arginine (250\u00a0mg\/kg, i.p.) along with pioglitazone. Visceral hypersensitivity, nociceptive thresholds, defecation frequency, stool form, serum and colon NO production and inducible (i) NOS activity were assessed 1\u00a0h after the final injection of pioglitazone or dimethylsulphoxide (used as the vehicle).<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Pioglitazone reduced visceral hypersensitivity and defecation frequency, increased nociceptive thresholds, NO production and <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content> activity and shifted stool form towards hard stools in D\u2010IBS rats. These effects of pioglitazone were significantly reversed by <jats:sc>l<\/jats:sc>\u2010NAME, but not GW9662. <jats:sc>l<\/jats:sc>\u2010Arginine augmented the effects of pioglitazone.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>In conclusion, pioglitazone alleviates symptoms in a rat model of D\u2010<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> through an <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\u2010dependent mechanism.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/1440-1681.12188","type":"journal-article","created":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T14:22:42Z","timestamp":1382970162000},"page":"118-126","source":"Crossref","is-referenced-by-count":34,"title":["Antinociceptive and antidiarrheal effects of pioglitazone in a rat model of diarrhoea\u2010predominant irritable bowel syndrome: Role of nitric 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