Background: Excess free radical production by neutrophils exacerbates tissue damage in GI ulceration. The gastric acid suppressant drugs (ASDs), famotidine and esomeprazole, are commonly used for GI ulcer treatment. These drugs have antioxidant properties in other species.
Objectives: Determine if ASDs reduce in vitro (2,2-diphenyl-1-picrylhydrazyl [DPPH]) and ex vivo (hydrogen peroxide [H2O2]) free radicals. Animals: Five healthy, client-owned dogs.
Methods: Standard curves (1.25-200 µg/ml of ASDs and Vitamin C [positive control]) were used to calculate the inhibitory concentration (IC50; concentration required to scavenge 50% of DPPH) of each compound via spectrofluorometry. Dog neutrophils were treated with famotidine (1, 10, 100 µg/ml), esomeprazole (8, 80, 800 µg/ml), vehicle (saline) or positive (apocynin; free radical scavenger) control, stimulated with phorbol 12-myristate 13-acetate, and resultant H2O2 quantified via relative luminescence units (RLUs). Experiments were repeated a minimum of three times, with triplicate samples per treatment. Normality was assessed (Shapiro-Wilk), and differences in IC50s or RLUs (mean + standard deviation) between groups analyzed (One Way ANOVA, Tukey’s multiple comparisons).
Results: Both ASDs were equivalent to Vitamin C IC50. Only 800 µg/ml esomeprazole significantly reduced H2O2 RLUs from stimulated neutrophils (53,867 + 4,957) compared to stimulated, untreated (606,667 + 81,132) and stimulated, saline-treated (662,000 + 28,000) groups (p< 0.01 for both). Esomeprazole-treated neutrophil RLUs were equivalent to that of apocynin. Conclusions and Clinical Importance: While both ASDs showed in vitro antioxidant effects, only esomeprazole reduced H2O2 ex vivo. This might be another mechanism by which esomeprazole resolves GI ulceration in dogs, independent of gastric acid suppression.
