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 hypergastri nemia secondary to an inhibitory effect on acid secretion, However, no body has given any explanation of the mechanism by which ciprofibrate and related phenoxyisobutyrate derivates inhibit acid secretion. Moreo ver, the reported inhibition of acid secretion has only been moderate, in contrast to the profound inhibition of acid secretion needed to in duce similar ECL-cell changes. To re-examine the effect of ciprofibrat e on gastric acidity and serum gastrin, we randomly assigned 33 male F isher rats into three treatment groups (100 or 20 mg/kg/day of ciprofi brate and control) during a period of 4 weeks, Daily assessments of ga stric acidity was done by gastric intubation, using a tube with a diam eter of 2.0 mm allowing the introduction of an infant pa-catheter, Mea surements were done in all animals 5 days a week. Ciprofibrate did not raise gastric pH, On the contrary, the highest dose increased the aci dity, Serum gastrin levels measured in blood taken by vein puncture be fore the initiation of the drug treatment and on the last day of the 4 week treatment period, revealed a dose-related significant hypergastr inemic effect of ciprofibrate, The slight increase in gastric acidity in the ciprofibrate high-dose group is most likely due to the hypergas trinemia provoked by the drug, This hypergastrinemia is therefore not secondary to an inhibition of acid secretion, but may be due to a dire ct effect of ciprofibrate on the G-cell. The ECL-cell hyperplasia and the ECL-cell carcinoids, which develop during treatment with peroxysom e-proliferators are thus due to hypergastrinemia, which is not seconda ry to inhibition of acid secretion.