Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model.

Abstract

The need for widely accepted and validated animal models to test the potential allergenicity and potency of novel (biotechnology-derived) proteins has become an important issue for their safety evaluation. In this article, we summarize the results of the development of an oral sensitization protocol for food proteins in the rat. Young Brown Norway rats were exposed to either various purified allergenic proteins (e.g., ovalbumin, partly purified), a whole food (cow's milk), or total protein extracts (hen's egg white, peanut) by daily gavage dosing during 42 days without the use of an adjuvant. The results showed that Brown Norway rats can be sensitized orally to the various allergenic food proteins tested, resulting in antigen-specific immunoglobulin (Ig) G and IgE responses, without the use of adjuvants. Animals orally exposed to cow's milk or total protein extracts of egg white also developed specific IgE and IgG antibodies that recognized the same proteins compared with antibodies from patients allergic to egg white or cow's milk. We also studied local and systemic immune-mediated effects. In ovalbumin-sensitized rats, some clinical symptoms of food allergy were studied upon an oral challenge with ovalbumin. The results demonstrated that gut permeability was increased and that in some animals breathing frequency and systolic blood pressure were temporarily decreased. The results obtained show that the Brown Norway rat provides a suitable animal model for food allergy research and for the study of relative allergenicity of existing and novel food proteins.

Effects of Transforming Growth Factor-Beta and Formula Feeding on Systemic Immune Responses to Dietary β-Lactoglobulin in Allergy-Prone Rats

“…The Brown Norway rat has a genetic predisposition to allergy development and has been successfully used as a model to induce allergic IgG and IgE responses to oral antigens (21)(22)(23)(24). Given the contradictory evidence of the role of breast-feeding in allergy development, we assessed at weaning (when TGF-␤ is still present in the diet) and postweaning (when TGF-␤ was no longer present in the diet), the immune response profile of allergy-prone Brown Norway rat pups either suckled naturally or fed formula with and without supplementation with the maternal milk cytokine TGF-␤.…”

Assessment of protein allergenicity on the basis of immune reactivity: animal models.

“…In conclusion the results obtained to date indicate that the BN rat might be a useful animal model in which to study the potential oral allergenicity of novel food proteins (Knippels and Penninks 2003). However, further testing with either whole food or with additional purified non-, weak-, and strongallergenic proteins is needed for a more indepth evaluation of this BN rat model.…”

Pulmonary Inflammation in Brown Norway Rats: Possible Association of Environmental Particles in the Animal Room Environment

“…It is conceivable that the spontaneous granulomatous inflammation was caused as a kind of allergic response. It was found that BN rats continuously administered OVA, whole protein extracts of hen's egg white or cow's milk are sensitized to those proteins [13]. In addition, BN rats were also susceptible to sensitization following topical exposure to the low molecular weight chemical, trimellitic anhydride [4].…”