16-16 dimethyl prostaglandin E2 reduces 5-fluorouracil-induced and mitomycin C-induced gastric mucosal injury in the dog.
Gastric complications occur in 5% to 20% of patients treated with hepatic artery infusion of chemotherapeutic agents for hepatic metastatic lesions. Often these complications are due to catheter dislodgement from the common hepatic artery into the left gastric artery. These studies were designed to answer the following questions: (1) Will chronic infusion of 5-fluorouracil into the left gastric artery produce mucosal injury in dogs; and (2) if so, will 16-16 dimethyl prostaglandin E2 afford protection against such injury? Mongrel dogs, 20 kg, were prepared with a polyethylene catheter in the left gastric artery and a Thomas cannula in the antrum 5 days prior to the study. Daily intraarterial infusions of either 5-fluorouracil, 6.7 mgM-2 X h-1, (N = 5) or 5-fluorouracil + 16-16 dimethyl prostaglandin E2, 2 micrograms X kg-1 X h-1, (N = 5) were given 12 hours a day for 5 days. In 2 dogs, 0.15 M NaCl was infused for 12 hours a day for 5 days as controls. Daily endoscopic evaluation of the gastric mucosa was made through the Thomas cannula by an unbiased observer and scored 0 to +5 based on degree of erythema, edema, friability, exudate, and gross ulceration. Results of these studies demonstrated that this dose of 5-fluorouracil had no effect on histamine-stimulated acid output. This dose of 16-16 dimethyl prostaglandin E2 inhibited histamine-stimulated maximal acid output 65%. From the observations made it was concluded that infusion of this chemotherapeutic regimen into the left gastric artery produced significant mucosal injury, simultaneous intraarterial infusion of 16-16 dimethyl prostaglandin E2 provided significant protection against this damage, and, since 16-16 dimethyl prostaglandin E2, at this dose, inhibits stimulated gastric acid secretion, it cannot be determined whether this observed mucosal protection is due to its antisecretory effect or some other mechanism.
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007261:Infusions, Intra-Arterial; D008297:Male; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000633:toxicity*; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage* / Q000627:therapeutic use
D008937:Mitomycins; D011459:Prostaglandins E, Synthetic; C017244:16,16-dimethylprostaglandin E; D016685:Mitomycin; D005472:Fluorouracil