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Updated: Aug 11, 2026

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Formation of a glutathione conjugate from butylated hydroxytoluene by rat liver microsomes
Abstract:
Butylated hydroxytoluene (BHT) was converted to S-(3,5-di-tert-butyl-4-hydroxybenzyl)-glutathione (BHT-glutathione) by rat liver microsomes in the presence of NADPH, molecular oxygen, and glutathione. NADH was far less effective than NADPH and exhibited little synergistic effect when used together with NADPH. Cytochrome P-450 inhibitors, such as SKF 525-A, alpha-naphthoflavone, metyrapone, and carbon monoxide, significantly inhibited BHT-glutathione formation. Liver microsomes from phenobarbital-treated rats catalyzed the formation of BHT-glutathione at a rate that was nine times the rate of adduct formation by control microsomes. No stimulation of BHT-glutathione formation was observed with the addition of liver cytosol fraction to the microsomal incubation mixtures even at low glutathione concentrations. These results support the view that BHT is converted by the cytochrome P-450 monooxygenases to a chemically reactive metabolite, possibly BHT-quinone methide, which forms BHT-glutathione by nonenzymatic conjugation with glutathione.
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