Esomeprazole Alters Neoplastic Canine Mast Cell Structure, Viability, and Function

Abstract: Background: Acid suppressant drugs are commonly used in dogs with either acid-related gastrointestinal disorders and/or mast cell tumors. Studies in humans suggest that acid suppressants possess potentially beneficial immunomodulatory and cytotoxic properties that have yet to be investigated in companion animals.

Objectives: To evaluate and compare the effects of esomeprazole, famotidine, and vehicle-treatment on mast cell (MC) ultrastructure, viability, and function in vitro, using both healthy and neoplastic MCs.

Methods: Both healthy (i.e., murine bone marrow derived [BMMC]) and neoplastic (i.e., human LAD2, canine C2 and BR) MC models were represented. Rat basophilic leukemic and canine B cell lymphoma cells served as granulocytic and agranulocytic controls, respectively. Differences in MC ultrastructure were assessed via light and transmission electron microscopy and MC viability was assessed using colorimetric assays (i.e., MTS) and flow cytometry. Changes in MC function were assessed via quantification of β-hexosaminidase release, indicative of degranulation. All experiments were performed in triplicate fashion, with Shapiro-Wilk, One-Way ANOVA and Dunnett’s post hoc tests used for analysis.

Results: Only esomeprazole-treated MCs of all lines exhibited qualitative and quantitative alterations in ultrastructure (i.e., increased cytoplasmic vacuolization, compromise of cell membrane), increased apoptosis, and altered degranulation responses. Esomeprazole was cytotoxic to all canine MCs (P < .001), but not to canine B cell lymphoma cells (P > .900).

Conclusions and clinical importance: Esomeprazole, but not famotidine, is cytotoxic to MCs, causing changes in structure and function. Treatment effects on granulocytes were pronounced, but those on canine lymphoma cells were not.