Comparative evaluation of different doses of PPAR-γ agonist alone and in combination with sulfasalazine in experimentally induced inflammatory bowel disease in rats

• Published in: Pharmacological reports 2013-07, Vol.65 (4), p.951-959
• Main Authors: D.S., Prasad Byrav, Medhi, Bikash, Prakash, Ajay, Chakrabarti, Amitava, Vaiphei, Kim, Khanduja, Krishan L.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Dose-Response Relationship, Drug; Drug Safety and Pharmacovigilance; Drug Therapy, Combination; Female; Inflammatory bowel disease; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - pathology; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Male; malondialdehyde; Malondialdehyde - metabolism; myeloperoxidase; Peroxidase - metabolism; Pharmacotherapy; Pharmacy; Pioglitazone; PPAR gamma - agonists; PPAR-γ; Rats; Sulfasalazine - pharmacology; Sulfasalazine - therapeutic use; Thiazolidinediones - pharmacology; Thiazolidinediones - therapeutic use; TNF-α; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(13)71076-4

Inflammatory bowel disease (IBD) is an idiopathic, chronic inflammatory condition, which affects the gastrointestinal tract and has no curative treatment. The present study aimed to investigate the effect of different doses of pioglitazone alone and in combination with sulfasalazine in TNBS (trinitrobenzenesulfonic acid)-induced inflammatory bowel disease (IBD) in rats. A total of 36 animals were included in the study. Animals were divided into five groups (n=6): group I – vehicle (ethanol), group II – TNBS + ethanol, group IIIA–TNBS + pioglitazone (15mg/kg), group IIIB – TNBS + pioglitazone (30mg/kg), group IV – TNBS + sulfasalazine (360mg/kg), group V – TNBS + sulfasalazine (360mg/kg) + pioglitazone (least effective dose found in group III). Group III was divided into two subgroups, namely ULA and IIIB, on the basis of different doses of pioglitazone used. After completion of two weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of intestinal inflammation, histological analysis, myeloperoxidase assay, malondialdehyde assay and TNF-α estimation. All the drug-treated groups showed both gross morphological and microscopic score either 1 or 2. None of them showed score of > 2 on both gross and microscopic morphological examination. Both MDA levels and MPO activity were significantly re-duced in the drug-treated groups, with maximum reduction seen in the combination group. TNF-α was reduced in pioglitazone group. It was highly reduced in sulfasalazine group (group V) as compared to TNBS group thereby indicating that pioglitazone is protective in TNBS-induced inflammatory bowel disease. The present study showed reduction in lipid peroxidation, malondialdehyde levels and TNF-α levels in pioglitazone-treated group and hence, there was significant improvement in gross and microscopic features, too. However, combination of pioglitazone and sulfasalazine has shown greater efficacy.