title: N,N'-Bis(5-aminosalicyl)-L-cystine is a potential colon-specific 5-aminosalicylic acid prodrug with dual therapeutic effects in experimental colitis.
abstract: To evaluate N,N'-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.
authors.affiliation: Laboratory of Biomedicinal Chemistry, College of Pharmacy, Pusan National University, Busan 609-735, South Korea.
authors.forename: Heejung
authors.initials: H
authors.lastname: Kim
authors.forename: Jeongsoon
authors.initials: J
authors.lastname: Huh
authors.forename: Hyunchu
authors.initials: H
authors.lastname: Jeon
authors.forename: Daekyu
authors.initials: D
authors.lastname: Choi
authors.forename: Jungoh
authors.initials: J
authors.lastname: Han
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
mesh_terms: D000636:Aminosalicylic Acids / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003553:Cystine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000636:Aminosalicylic Acids; C528877:N,N'-bis(5-aminosalicyl)cystine; D011355:Prodrugs; D003553:Cystine