Antioxidant therapy with N-acetylcysteine plus mesalamine accelerates mucosal healing in a rodent model of colitis.
The aims of this study were to examine the ability of the antioxidant N-acetylcysteine (NAC) and mesalamine (5-ASA) alone and in combination to affect TNBS-induced colitis in rat. Three days following induction of TNBS colitis rats were randomized to receive daily intracolonic treatment with NAC, 5-ASA, and NAC plus 5-ASA for 5 or 8 days. At the end of the treatment period macroscopic and microscopic colonic injuries were scored. Myeloperoxidase (MPO) activity and cytokine gene expression were measured in colonic tissues. Results indicated that treatment with NAC plus 5-ASA caused a significantly greater reduction in colonic injury than either agent alone. Furthermore, combination therapy inhibited significantly MPO activity and inflammatory cytokine gene expression in the distal colon of TNBS-treated animals. The beneficial effects of NAC plus 5-ASA on reduction of colonic injury and promotion of healing were most evident after 8 days of treatment.
Siddiqui
Ali
A
Division of Gastroenterology, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Ancha
Hanumantha
H
Tedesco
Dustin
D
Lightfoot
Stanley
S
Stewart
Charles A
CA
Harty
Richard F
RF
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001707:Biopsy, Needle; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D019804:Mesalamine; D009195:Peroxidase; D000111:Acetylcysteine