The peroxisome-proliferator ciprofibrate induces hypergastrinemia without raising gastric pH.
The ECL-cell hyperplasia and ECL-cell carcinoids occurring during long-term treatment with ciprofibrate, have been attributed to hypergastrinemia secondary to an inhibitory effect on acid secretion. However, nobody has given any explanation of the mechanism by which ciprofibrate and related phenoxyisobutyrate derivates inhibit acid secretion. Moreover, the reported inhibition of acid secretion has only been moderate, in contrast to the profound inhibition of acid secretion needed to induce similar ECL-cell changes. To re-examine the effect of ciprofibrate on gastric acidity and serum gastrin, we randomly assigned 33 male Fisher rats into three treatment groups (100 or 20 mg/kg/day of ciprofibrate and control) during a period of 4 weeks. Daily assessments of gastric acidity was done by gastric intubation, using a tube with a diameter of 2.0 mm allowing the introduction of an infant pH-catheter. Measurements were done in all animals 5 days a week. Ciprofibrate did not raise gastric pH. On the contrary, the highest dose increased the acidity. Serum gastrin levels measured in blood taken by vein puncture before the initiation of the drug treatment and on the last day of the 4 week treatment period, revealed a dose-related significant hypergastrinemic effect of ciprofibrate. The slight increase in gastric acidity in the ciprofibrate high-dose group is most likely due to the hypergastrinemia provoked by the drug. This hypergastrinemia is therefore not secondary to an inhibition of acid secretion, but may be due to a direct effect of ciprofibrate on the G-cell. The ECL-cell hyperplasia and the ECL-cell carcinoids, which develop during treatment with peroxysome-proliferators are thus due to hypergastrinemia, which is not secondary to inhibition of acid secretion.
Department of Medicine, Trondheim University Hospital, Norway.
T C
TC
Martinsen
N
N
Nesjan
K
K
Rønning
A K
AK
Sandvik
H L
HL
Waldum
D000818:Animals; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D058607:Fibric Acids; D005750:Gastric Juice / Q000737:chemistry; D005755:Gastrins / Q000097:blood*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000187:drug effects / Q000502:physiology
D058607:Fibric Acids; D005755:Gastrins; D002995:Clofibric Acid; C019304:ciprofibrate