Cytochrome P450 destruction by benzene metabolites 1,4-benzoquinone and 1,4-hydroquinone and the formation of hydroxyl radicals in minipig liver microsomes

摘要: Reactive metabolites of benzene 1,4-benzoquinone and 1,4-hydroquinone exert their toxic effects through covalent and/or oxidative damage to DNA proteins. Since minipigs have been proposed as a suitable model species in toxicological pharmacological research, the aim this study was explore mechanisms by which catechol, destroy cytochrome P450 (P450) induce stress minipig liver microsomes. Our second goal assess usefulness microsomes system for testing production clinically relevant quinone-containing compounds, e.g. anthracyclines. Of three tested, highest destruction caused 1,4-benzoquinone. This destructive effect did not correlate with hydroxyl radicals measured ESR spin trapping samples containing 1,4-hydroquinone. results confirm previous findings that exerts its mainly direct attack on macromolecules while rather stimulates reactive oxygen species. Doxorubicin stimulated similarly Minipig should be further tested possibly potential modulators toxicity doxorubicin.