Prostaglandins modulate gut epithelial cell proliferation and survival. Prostaglandins are synthesized from arachi-donic acid by either of two cyclo-oxygenases (COX) — COX-1 or COX-2. COX-1 is constitutively expressed, and COX-2 is inducible by cytokines and by various other stimuli. Indomethacin, an inhibitor of COX-1 and COX-2, further reduces the number of surviving crypt cells in irradiated mice. Dimethyl PGE2 reversed the indomethacin-induced decrease in crypt survival, whereas selected COX-2 inhibitors had no effect on crypt cell survival. This suggests that radiation injury results in increased COX-1 levels in the crypt stem cells and their progeny and that PGE2 produced through COX-1 promotes crypt stem cell survival and proliferation. Choose a perfect online pharmacy to get cialis professional and treat your health issue.
Clinical learning point: Radiation may increase the constitutively expressed COX-1 in the intestine, and nonsteroidal anti-inflammatory drugs such as indo-methacin may worsen this radiation-induced damage. The role of prostaglandins in protecting the intestine from the development of radiation enteritis remains to be determined.
Methotrexate (MTX) is used in the management of patients with osteosarcoma, rheumatoid arthritis and inflammatory bowel disease. Some patients treated with MTX experience nausea, vomiting, diarrhea, gastrointestinal ulceration, stomatitis and mucositis. The surface area of the intestine may be reduced by MTX treatment, and there may be associated diminution in the absorption of some drugs. Following MTX administration to mice, intestinal permeability to phenol red and fluoresceine isothiocyanate is increased. The side effects of MTX in humans can be reduced by the coadministration of folic acid.