The glutathione conjugates of tert-butyl hydroquinone as potent redox cycling agents and possible reactive agents underlying the toxicity of butylated hydroxyanisole.
The glutathione conjugates of tert-butyl hydroquinone, a metabolite of butylated hydroxyanisole (BHA), possess redox potentials which are much higher as compared to the non-conjugated hydroquinone (0.36 V for the hydroquinone and 1.2-1.4 V for the conjugates). As a result, the redox cycling activity of the conjugates, as measured by oxygen consumption in the presence of a reducing agent, is increased tenfold as compared to the non-conjugated hydroquinone. Since evidence for both oxidative damage and the involvement for glutathione in the toxicity of butylated hydroxyanisole is available, this mechanism may be involved in the toxic action of this compound.
van Ommen
B
B
TNO Toxicology and Nutrition Institute, Dept. of Biological Toxicology, Zeist, The Netherlands.
Koster
A
A
Verhagen
H
H
van Bladeren
P J
PJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry; D002083:Butylated Hydroxyanisole / Q000633:toxicity*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship
D000975:Antioxidants; D006873:Hydroquinones; C078417:5-(S-glutathionyl)-2-tert-butylhydroquinone; C078416:6-(S-glutathionyl)-2-tert-butylhydroquinone; D002083:Butylated Hydroxyanisole; C018855:2-tert-butylhydroquinone; D005978:Glutathione; D001205:Ascorbic Acid