Co-oxidation-mediated xenobiotic activation and cytotoxicity by 12-lipoxygenase in intact platelets

Toxicology
Kyung-Min LimJin-Ho Chung

Abstract

Peroxidase-mediated co-oxidation process has been suggested as a major alternative pathway for xenobiotic bioactivation other than hepatic cytochrome P450 monooxygenase system. Despite the wealth of reports on the possible involvement of co-oxidation in bioactivation of various compounds, clear manifestation of co-oxidation-mediated xenobiotic bioactivation in intact cell system without extra sources of peroxidase system has been difficult to demonstrate, mainly due to the natural scarcity of peroxidase activities in fresh intact cells. In the present study, arachidonic acid (AA) dependent bioactivation of alpha-naphthol, a representative phenolic compound, was demonstrated as shown by covalent binding increases in alpha-naphthol concentration dependent manner in freshly prepared intact platelets, where two AA dependent representative peroxidases, 12-lipoxygenase (12-LOX) and prostaglandin H synthase (PHS) are abundantly expressed. Inhibitors of 12-LOX attenuated the covalent binding of alpha-naphthol while inhibitors of PHS were not effective, indicating the predominant role of 12-LOX in AA-initiated co-oxidation in intact platelets. In addition, free radical scavengers and thiol donors prevented effectively the bioactivation ...Continue Reading

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Citations

Jun 22, 2010·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Hana BártíkováBarbora Szotáková
Jan 21, 2021·Journal of Applied Toxicology : JAT·Piaopiao ZhaoGuixia Liu

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