Formation of ortho-phenylphenol glutathione conjugates in the rat liver.
1. The radioactive materials(s) derived from 14C-ortho-phenylphenol (OPP) became bound irreversibly to hepatic microsomal macromolecules in an NADPH-generating system, and the binding was inhibited by cysteine and glutathione (GSH). 2. A water-soluble phenyl-hydroquinol (PHQ)-GSH conjugate was produced by non-enzymic reaction between phenyl-p-benzoquinone and GSH in alcoholic aqueous solution, and the structure of the conjugate was confirmed by its 13C-n.m.r. spectrum. 3. When 14C-OPP and GSH were incubated in a microsomal NADPH-generating system, radioactive material derived from the aqueous phase of the incubation mixture was similar to the synthetic PHQ-GSH on t.l.c. 4. PHQ-GSH was excreted as a minor conjugate into the bile after oral administration of OPP (1000 mg/kg) to rats, the cumulative biliary excretion of the conjugate was about 4% of the dose in 6 h.
Nakagawa
Y
Y
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Tayama
S
S
D000818:Animals; D001646:Bile / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D001713:Biphenyl Compounds; D009249:NADP; C004369:2-phenylphenol; D005978:Glutathione