title: Comparative evaluation of different doses of PPAR-γ agonist alone and in combination with sulfasalazine in experimentally induced inflammatory bowel disease in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 (15 mg/kg), group IIIB--TNBS + pioglitazone (30 mg/kg), group IV--TNBS + sulfasalazine (360 mg/kg), group V--TNBS + sulfasalazine (360 mg/kg) + pioglitazone (least effective dose found in group III). Group III was divided into two subgroups, namely IIIA 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.
  
  
  RESULTS
  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 reduced 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Research Block: B, Sector: 12, PGIMER, Chandigarh, India 160012. drbikashus@yahoo.com.
authors.forename: Prasad
authors.initials: P
authors.lastname: Byrav D S
authors.forename: Bikash
authors.initials: B
authors.lastname: Medhi
authors.forename: Ajay
authors.initials: A
authors.lastname: Prakash
authors.forename: Amitava
authors.initials: A
authors.lastname: Chakrabarti
authors.forename: Kim
authors.initials: K
authors.lastname: Vaiphei
authors.forename: Krishan L
authors.initials: KL
authors.lastname: Khanduja
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D009195:Peroxidase / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D012460:Sulfasalazine / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D000077205:Pioglitazone