Enhancement of allergic responses in vivo and in vitro by butylated hydroxytoluene

• Published in: Toxicology and applied pharmacology 2007-09, Vol.223 (2), p.164-172
• Main Authors: Yamaki, Kouya, Taneda, Shinji, Yanagisawa, Rie, Inoue, Ken-ichiro, Takano, Hirohisa, Yoshino, Shin
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Akt; ALBUMINS; Allergy; ANAPHYLAXIS; Animals; ANTIGENS; ANTIOXIDANTS; Antioxidants - toxicity; ASTHMA; beta-N-Acetylhexosaminidases - metabolism; Biological and medical sciences; BLOOD SERUM; Butylated hydroxytoluene; Butylated Hydroxytoluene - toxicity; Calcium - analysis; Calcium - metabolism; CALCIUM IONS; Cell Degranulation - drug effects; Cell Line, Tumor; Degranulation; DINITROPHENOL; Dinitrophenols - chemistry; Dinitrophenols - toxicity; Dose-Response Relationship, Drug; HISTAMINE; Histamine Release - drug effects; Hypersensitivity - etiology; Hypersensitivity - metabolism; IgE; IN VITRO; IN VIVO; INJECTION; Intracellular Fluid - chemistry; Intracellular Fluid - drug effects; Ionomycin - toxicity; Ionophores - toxicity; Male; MAST CELLS; Medical sciences; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; PHOSPHORYLATION; Phosphorylation - drug effects; PI3K; POLAR-CAP ABSORPTION; Proto-Oncogene Proteins c-akt - metabolism; RATS; Rats, Sprague-Dawley; RBL2H3; Receptors, IgE - metabolism; Time Factors; Toxicology; TYROSINE; Tyrosine - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2007.05.007

The effect of butylated hydroxytoluene (BHT), which is used widely as an antioxidant, on IgE-dependent allergic responses in vivo and in vitro was investigated. For in vivo study, passive cutaneous anaphylaxis (PCA) was elicited in rats by i.d. injection of anti-DNP IgE and 48 h later by i.v. injection of DNP-HSA. BHT was i.p. given immediately after anti-DNP IgE injection. For in vitro studies, the rat mast cell line RBL2H3 sensitized with monoclonal anti-dinitrophenol (DNP) IgE was challenged with the multivalent antigen DNP-human serum albumin (DNP-HSA) in the presence or absence of BHT. β-Hexosaminidase and histamine released from RBL2H3 cells, as indicators of degranulation of the cells, the concentration of intracellular Ca 2+, the level of phosphorylated-Akt, and global tyrosine phosphorylation as indicators of mast cell activation, were measured. The results showed that BHT given to anti-DNP IgE-sensitized rats augmented DNP-specific PCA in a dose-dependent manner. In the presence of BHT, IgE-induced releases of β-hexosaminidase and histamine from RBL2H3 cells were increased. BHT also further elevated IgE-mediated increased concentrations of intracellular Ca 2+ and the levels of phosphorylated-Akt, but did not affect global tyrosine phosphorylation, in RBL2H3 cells. Moreover, the PI3K inhibitor LY294002 inhibited IgE-dependent degranulation and its enhancement by BHT. These findings indicate that BHT may upregulate PCA by enhancing mast cell degranulation associated with enhancements of intracellular Ca 2+ concentration and PI3K activation, suggesting that BHT might affect allergic diseases such as allergic rhinitis and asthma.