Enhancement of butylated hydroxytoluene-induced mouse lung damage by butylated hydroxyanisole. 1988

D C Thompson, and M A Trush
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205.

The phenolic antioxidant butylated hydroxytoluene (BHT) is known to produce a dose-dependent increase in mouse lung weight which is characterized by the necrosis of pulmonary type I and endothelial cells. We studied the ability of butylated hydroxyanisole (BHA) to modify BHT-induced changes in lung weight in male CD-1 mice. BHA alone had no effect on lung weight up to a dose of 500 mg/kg (sc). However, when injected 30 minutes prior to sub-threshold doses of BHT (0-250 mg/kg, ip), BHA significantly enhanced lung weight in a dose-dependent manner. The ability of BHA to enhance BHT-induced changes in lung weight was dependent on both the time and the route of administration of BHA relative to BHT. Deuteration of BHT abolished the in vivo toxicity from the combination of BHA and BHT. These results suggest that the toxicity resulting from the combination of BHA and BHT is due to the formation of BHT-quinone methide and that the role of BHA might be either to deplete some protective mechanism in the target pulmonary cells or to enhance the biotransformation of BHT into BHT-quinone methide.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D011809 Quinones Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
D002083 Butylated Hydroxyanisole Mixture of 2- and 3-tert-butyl-4-methoxyphenols that is used as an antioxidant in foods, cosmetics, and pharmaceuticals. Butylhydroxyanisole,(1,1-Dimethylethyl)-4-methoxyphenol,AMIF-72,BHA,Butyl Methoxyphenol,Embanox,Nipantiox 1-F,Tenox BHA,AMIF 72,AMIF72,Hydroxyanisole, Butylated,Methoxyphenol, Butyl,Nipantiox 1 F,Nipantiox 1F
D002084 Butylated Hydroxytoluene A di-tert-butyl PHENOL with antioxidant properties. Butylhydroxytoluene,2,6-Bis(1,1-dimethylethyl)-4-methylphenol,2,6-Di-t-butyl-4-methylphenol,2,6-Di-tert-butyl-4-methylphenol,2,6-Di-tert-butyl-p-cresol,4-Methyl-2,6-ditertbutylphenol,BHT,Di-tert-butyl-methylphenol,Dibunol,Ionol,Ionol (BHT),2,6 Di t butyl 4 methylphenol,2,6 Di tert butyl 4 methylphenol,2,6 Di tert butyl p cresol,4 Methyl 2,6 ditertbutylphenol,Di tert butyl methylphenol,Hydroxytoluene, Butylated
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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