N,N′-Bis(5-aminosalicyl)-L-cystine is a potential colon-specific 5-aminosalicylic acid prodrug with dual therapeutic effects in experimental colitis
✍ Scribed by Heejung Kim; Jeongsoon Huh; Hyunchu Jeon; Daekyu Choi; Jungoh Han; Youngmi Kim; Yunjin Jung
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 215 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
To evaluate N,N 0 -bis(5-aminosalicyl)-L-cystine (5-ASA-Cys) as a potential colon-specific 5-aminosalicylic acid prodrug with dual therapeutic effects in experimental colitis, the pharmacokinetics and therapeutic activity were investigated after oral administration of 5-ASA-Cys and amelioration of experimental colitis was compared after rectal administration of 5-aminosalicylic acid (5-ASA) and/or cysteine. In addition, the gluthathione (GSH) level in the inflamed colonic tissue was examined after administration of cysteine or 5-ASA-Cys. Oral administration of 5-ASA-Cys delivered much greater amount of 5-ASA to the large intestine and excreted lower amount of 5-ASA via urine than that of free 5-ASA. Oral administration of 5-ASA-Cys ameliorated experimental colitis of rats induced by TNBS, which was more effective than that of sulfasalazine. Although cysteine administered rectally was not significantly effective, intracolonic treatment with both 5-ASA and cysteine showed a synergic effect in alleviating the rat colitis. Furthermore, not only 5-ASA-Cys administered orally but also cysteine administered rectally increased the glutathione level in the inflamed colonic tissue. Taken together, these results suggest that 5-ASA-Cys is a potential colon specific 5-ASA prodrug with dual therapeutic effects on experimental colitis and cysteine modulation of the glutathione level may be relevant to the dual effects of the prodrug.