P-087: Phosphatidylcholine (PC)-conjugated 5ASA accelerates recovery from dextran sulfate sodium (DSS) colitis in rats

Background and Purpose

Though multiple therapies have been advanced for the treatment of Inflammatory Bowel Disease (IBD), 5-Amino Salicylic Acid (5ASA) continues to have an important role both in active disease states and in maintenance of remission. We describe the synergistic and protective effects of phosphatidylcholine (PC) conjugate of 5ASA in an animal model of colitis.

Methods

Male Sprague Dawley rats were randomly distributed among four treatment groups. Colitis was induced in three groups by adding 4% dextran sulfate sodium (DSS) to the drinking water for 6 days, and the 4^th group served as a non-DSS control. After the completion of the 6-day course of DSS, rats were intragastrically administered 1 ml of: saline, 5ASA (50mg/kg) and an equivalent dose of PC-5ASA. All rats were euthanized at the end of day 9, at which time fecal hemoglobin, colonic weight/length, myeloperoxidase (MPO)/protein, and histology were evaluated. Histological evidence of colonic injury was determined by a numerical scale from 0 (normal) to 4 (severe injury extending to the base of the crypt).

Results

DSS induced a significant 2-4 fold increase in tissue edema, inflammation and gastrointestinal bleeding as indicated by increases in tissue weight/length, MPO specific activity and fecal hemoglobin respectively. These colitis-induced changes were partially reversed by 5ASA, and fully reversed (p<0.05) in rats treated with PC-5ASA during the post-DSS 3 day recovery period. PC-5ASA treatment also conferred significant histological protection against DSS-induced colitis in comparison to rats treated with unmodified 5ASA or saline.

Conclusion

PC-5ASA provided enhanced recovery from DSS-induced colitis in comparison to 5ASA in rats, based upon a number of indices of mucosal inflammation, histology and fecal blood loss, and may represent a novel formulation to therapeutically manage IBD. Future studies are planned in other animal models of colitis and in clinical trials on IBD patients to confirm these encouraging observations. Supported by Cambrex Corp and PLx Pharma Inc and NIH training grant T32-DK07664.