Effect of different doses of thalidomide in experimentally induced inflammatory bowel disease in rats.
The present study was carried out to evaluate the effect of different doses of thalidomide in experimentally induced inflammatory bowel disease in rats. Adult Wistar rats of either sex were used (n = 36). Colitis was induced by a single intra-colonic application of 20 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in 35% ethanol into the descending colon. Rats were divided into six groups (n = 6). Animals were treated with vehicle (ethanol), TNBS dissolved in 35% ethanol, thalidomide (with different doses of 50, 100 and 150 mg/kg body weight), and sulfasalazine (360 mg/kg body weight) for 14 days. After completion of 14 days of treatment, animals were killed and the following parameters were assessed: morphological score, histological score and biochemical parameters (myeloperoxidase, malondialdehyde and tumour necrosis factor-alpha). Results showed thalidomide with different doses provided protection against TNBS-induced colonic damage. There was significant protection with thalidomide 150 mg/kg body weight compared to controls (P < 0.001). All the biochemical parameters were highly reduced in the entire thalidomide-treated group compared to controls particularly with thalidomide 150 mg/kg body weight (P < 0.001). Treatment with thalidomide restored malondialdehyde as well as reduction of myeloperoxidase and tumour necrosis factor-alpha towards normal levels. Morphological and histological score were significantly reduced in all the treated groups with significant effect found with 150 mg/kg (P < 0.001). Our results indicate efficacy of thalidomide in TNBS induce experimental colitis model in rats but present findings requires further investigation to establish the real safety and efficacy in human beings.
Prakash
Om
O
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Medhi
Bikash
B
Saikia
Uma Nahar
UN
Pandhi
Promila
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013792:Thalidomide / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D008315:Malondialdehyde; D013792:Thalidomide; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase