Biological fate of butylated hydroxytoluene (BHT); Binding in vitro of BHT to liver microsomes.

Abstract

The binding of ¹⁴C-labeled butylated hydroxytoluene (¹⁴C-BHT) to the liver microsomes was studied in vitro. Binding of ¹⁴C-BHT to microsomal macromolecules was linear with time and protein concentration. Oxygen and dihydronicotinamide adenine dinucleotide phosphate (NADPH) were necessary for this binding, while carbon monoxide or SKF-525A inhibited it. It is indicated that a cytochrome P-450-linked monooxygenase system mediated the binding. In addition the binding was more pronounced in the liver microsomes from animals pretreated with inducers (phenobarbital or BHT) of microsomal monooxygenase system. From the effects of pretreatment with these inducers, it is suggested that a cytochrome P-450 with a high BHT oxidase activity is mainly responsible for the metabolic activation of BHT in the liver microsomes. The microsomes in the brain, kidneys and spleen were devoid of BHT-binding capacity, but in the lung microsomes the binding capacity was about 40% of that in the liver microsomes.