Radiation lethality potentiation in total body irradiated mice by a commonly prescribed proton pump inhibitor, Pantoprazole sodium

Abstract

Purpose: Pantoprazole sodium (Protonix) is a proton pump inhibitor (PPI) widely used to treat peptic ulcer and gastroesophageal reflux due to its ability to inhibit gastric acid secretion. Therefore, a large group of the population exposed to total body irradiation (TBI) in the event of a nuclear disaster would be on this or similar medications. We investigated the effect of pantoprazole on TBI-induced lethality in mice.Methods and materials: Male CD2F1 mice were exposed to various doses of uniform TBI using a 137Cs irradiator. Pantoprazole was administered by twice daily subcutaneous injection in saline from 4 days before to 5 days after irradiation. Effects on gastric pH, and gastrointestinal (GI) and hematopoietic toxicity were evaluated.Results: Pantoprazole administration significantly exacerbated 30 day lethality and gastrointestinal toxicity. Median survival after 9.0 Gy TBI was reduced from 22 days to 12 days (p = 0.006). Pantoprazole adversely effected intestinal crypt survival and mucosal surface area. In contrast, equivalent doses of a histamine type-2(H2) receptor blocker (cimetidine) did not alter TBI-induced lethality.Conclusion: The adverse effect of pantoprazole on TBI-induced lethality is highly important because of the widespread use of PPI in the general population, as well as use of these drugs for acid suppression in individuals exposed to radiation. Further studies of the mechanisms underlying the adverse effect of PPI after exposure to TBI are clearly warranted. Until results from such studies are available, other acid-suppressing strategies should be preferred in the context of radiation exposure.