The Nrf2 activator, tBHQ, exacerbates immediate hypersensitivity response to food allergen (HYP7P.315)

Abstract

Nuclear erythroid 2 related factor 2 (Nrf2) is a transcription factor activated by cell stress, including oxidative and electrophilic stimuli, resulting in the upregulation of cytoprotective genes. Nrf2 can be activated experimentally by a number of different pharmacological agents, including tert-butylhydroquinone (tBHQ), which is also used commercially as a food additive. We recently showed that activation of Nrf2 by tBHQ promotes Th2 differentiation and inhibits Th1 differentiation in isolated CD4+ T cells. Given that tBHQ is a food additive and promotes Th2 differentiation, the purpose of the present studies was to determine the effect of tBHQ in a mouse model of food allergy. Mice were administered a diet either with or without tBHQ (0.001%) for two weeks prior to sensitization with ovalbumin. Notably, this dose of tBHQ is lower than that normally present in standard rodent chow (0.0016%). The mice were sensitized weekly transdermally for 4 weeks. Sensitization to ovalbumin caused an increase in ovalbumin-specific IgE in plasma, which was greater in animals exposed to tBHQ. After sensitization, the mice were orally challenged with ovalbumin, causing mild/moderate immediate hypersensitivity, which was exacerbated by tBHQ. Overall, these studies suggest that low doses of the food additive, tBHQ, increase IgE response to food allergen and exacerbate clinical signs of immediate hypersensitivity. (This work was funded by NIH grant: ES018885.)