Misoprostol accelerates colonic mucosal repair in acetic acid-induced colitis.
The objectives of this study were 1) to determine whether misoprostol (MISO) (prostaglandin E1 analog) pretreatment protects the colonic mucosa from the injurious effects of acetic acid by attenuating the initial injury or by enhancing the rate of repair and 2) to assess the relationship between the protective effect of MISO pretreatment and mucosal ornithine decarboxylase activity in the inflamed colon. We found that the intrarectal administration of acetic acid caused rapid and extensive injury to the colonic mucosa, such that mucosal permeability increased 88-, 75-, 26-, 7.5- and 9.3-fold at 1, 2, 6, 24 and 48 hr after the enema, respectively. Intrarectal pretreatment with 50 micrograms of MISO for 30 min did not attenuate the increase in mucosal permeability at 1 hr after enema; however, it did significantly reduce mucosal permeability by 50 to 60% at 2, 6 and 48 hr after enema. We also demonstrated that acetic acid produced an 8.4-fold increase in colonic myeloperoxidase activity and a 1.8-fold increase in colonic weight at 48 hr after enema. MISO significantly reduced the increases in both myeloperoxidase activity and colon weight. Ornithine decarboxylase activity in the descending colon of vehicle-pretreated animals increased significantly only at 24 hr after the acetic acid enema. In addition, MISO pretreatment followed by acetic acid enema resulted in significantly higher ornithine decarboxylase activities in the descending colon at 2 and 6 hr, compared with the vehicle plus acetic acid and MISO plus saline groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamada
T
T
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130.
Fujimoto
K
K
Tso
P
P
Fujimoto
T
T
Gaginella
T S
TS
Grisham
M B
MB
D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D003109:Colonic Diseases, Functional / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D004760:Enterocolitis / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008297:Male; D016595:Misoprostol / Q000494:pharmacology* / Q000627:therapeutic use; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000085:Acetates; D011073:Polyamines; D016595:Misoprostol; D009955:Ornithine Decarboxylase; D019342:Acetic Acid