Effects of oxytetracycline on the rat exocrine pancreas.

Objectives: Given the appearance of pancreatitis attributed to tetracycline, as described in the literature, we have investigated its effect on the enzymatic content of pancreas and duodenal fluid and on pancreatic ultrastructure. We have evaluated possible differences between sexes and the relation of our findings with those described in the initial phases of acute pancreatitis, in the context of the acinar hypothesis.

Methods: With 128 Wistar rats (63 male and 65 female), 3 groups were established: control (group I) experimental animals treated with oxytetracycline intramuscularly, 15 and 30 mg/kg/d (groups II and III, respectively). Before sacrifice, half of the rats in each group were stimulated with cholecystokinin. Blood, pancreatic tissue (for enzyme dosage and morphological study), and duodenal fluid were extracted following anesthesia.

Results: The stimulated males of group III presented lower amylase levels in pancreatic tissue and duodenal fluid (P < 0.003). Just the opposite occurred in female rats. A similar tendency was observed with other enzymes (lipase and trypsin). Zymogen granule counts, appearance of immature granules, and dilation of ergastoplasm were more frequent in the stimulated animals.

Conclusions: Oxytetracycline seems to induce morphofunctional changes in rat pancreas, which differ according to sex. In the female, enzyme accumulation that could predispose intracellular activation seems to exist, as well as the ultrastructural findings described in initial phases of acute experimental pancreatitis. This agrees with the greater frequency of pancreatitis in women undergoing tetracycline treatment described in the literature. In contrast, for males the findings were more compatible with decrease of protein synthesis. This would make them less susceptible to crinophagy phenomena and, thus, to acute pancreatitis in the context of the acinar or lysosome hypothesis.