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Oxidation of hydroquinone by copper: chemical mechanism and biological effects.
Arch Biochem Biophys. 1993 Jan; 300(1):346-55.AB

Abstract

Exposure of humans and experimental animals to benzene has been shown to result in hematotoxicity such as pancytopenia, aplastic anemia, and leukemia. The oxidative activation of the benzene metabolite, hydroquinone (HQ), in the bone marrow to the electrophilic benzoquinone (BQ) has been suggested to play an important role in benzene-induced hematotoxicity. Since the interaction of several xenobiotics with copper has been shown to result in their metabolism, in this study we have investigated the role of copper in the oxidation of HQ and HQ-induced toxicity to mice bone marrow stromal cells, target cells of HQ in the bone marrow. In phosphate-buffered saline, HQ underwent autoxidation slowly to BQ, while the presence of Cu(II) ions (1, 2.5, 5, 10, 50 microM) strongly accelerated the oxidation of HQ to BQ in a concentration-dependent manner. Reaction of HQ with Cu(II) was also accompanied by the reduction of Cu(II) to Cu(I), the utilization of O2, and the concomitant generation of H2O2. The oxidation of HQ by Cu(II) could be blocked by the Cu(I)-specific chelator bathocuproinedisulfonic acid (BCS), particularly when the ratio of BCS to Cu(II) was 4:1. By observing the kinetics of the reactions derived from mixing 100 microM HQ and 100 microM Cu(II), it was found that all of the Cu(II) was reduced to Cu(I) within 5 s, followed by consumption of O2 and the generation of BQ, which reached maximum levels at 4 min after mixing HQ and Cu(II). In addition, oxidation of HQ by Cu(II) also generated chemiluminescence. In the presence of myeloperoxidase, Cu(II)-mediated oxidation of HQ was increased. Addition of Cu(II) to primary bone marrow stromal cell cultures significantly enhanced HQ-induced cytotoxicity. The enhanced cytotoxicity of HQ by Cu(II) could be completely prevented by adding BCS, glutathione (GSH), or dithiothreitol but not by catalase. Supplementation of stromal cells with 20 microM BCS in the absence of exogenously added Cu(II) significantly abated HQ-induced cellular GSH depletion and cytotoxicity, suggesting a possible involvement of endogenous copper in the activation of HQ. The above results indicate that Cu(II) strongly induces the oxidation of HQ and as such may be a factor involved in the oxidative activation and toxicity of HQ in target cells.

Authors+Show Affiliations

Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8424668

Citation

Li, Y, and M A. Trush. "Oxidation of Hydroquinone By Copper: Chemical Mechanism and Biological Effects." Archives of Biochemistry and Biophysics, vol. 300, no. 1, 1993, pp. 346-55.
Li Y, Trush MA. Oxidation of hydroquinone by copper: chemical mechanism and biological effects. Arch Biochem Biophys. 1993;300(1):346-55.
Li, Y., & Trush, M. A. (1993). Oxidation of hydroquinone by copper: chemical mechanism and biological effects. Archives of Biochemistry and Biophysics, 300(1), 346-55.
Li Y, Trush MA. Oxidation of Hydroquinone By Copper: Chemical Mechanism and Biological Effects. Arch Biochem Biophys. 1993;300(1):346-55. PubMed PMID: 8424668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidation of hydroquinone by copper: chemical mechanism and biological effects. AU - Li,Y, AU - Trush,M A, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - 346 EP - 55 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 300 IS - 1 N2 - Exposure of humans and experimental animals to benzene has been shown to result in hematotoxicity such as pancytopenia, aplastic anemia, and leukemia. The oxidative activation of the benzene metabolite, hydroquinone (HQ), in the bone marrow to the electrophilic benzoquinone (BQ) has been suggested to play an important role in benzene-induced hematotoxicity. Since the interaction of several xenobiotics with copper has been shown to result in their metabolism, in this study we have investigated the role of copper in the oxidation of HQ and HQ-induced toxicity to mice bone marrow stromal cells, target cells of HQ in the bone marrow. In phosphate-buffered saline, HQ underwent autoxidation slowly to BQ, while the presence of Cu(II) ions (1, 2.5, 5, 10, 50 microM) strongly accelerated the oxidation of HQ to BQ in a concentration-dependent manner. Reaction of HQ with Cu(II) was also accompanied by the reduction of Cu(II) to Cu(I), the utilization of O2, and the concomitant generation of H2O2. The oxidation of HQ by Cu(II) could be blocked by the Cu(I)-specific chelator bathocuproinedisulfonic acid (BCS), particularly when the ratio of BCS to Cu(II) was 4:1. By observing the kinetics of the reactions derived from mixing 100 microM HQ and 100 microM Cu(II), it was found that all of the Cu(II) was reduced to Cu(I) within 5 s, followed by consumption of O2 and the generation of BQ, which reached maximum levels at 4 min after mixing HQ and Cu(II). In addition, oxidation of HQ by Cu(II) also generated chemiluminescence. In the presence of myeloperoxidase, Cu(II)-mediated oxidation of HQ was increased. Addition of Cu(II) to primary bone marrow stromal cell cultures significantly enhanced HQ-induced cytotoxicity. The enhanced cytotoxicity of HQ by Cu(II) could be completely prevented by adding BCS, glutathione (GSH), or dithiothreitol but not by catalase. Supplementation of stromal cells with 20 microM BCS in the absence of exogenously added Cu(II) significantly abated HQ-induced cellular GSH depletion and cytotoxicity, suggesting a possible involvement of endogenous copper in the activation of HQ. The above results indicate that Cu(II) strongly induces the oxidation of HQ and as such may be a factor involved in the oxidative activation and toxicity of HQ in target cells. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/8424668/Oxidation_of_hydroquinone_by_copper:_chemical_mechanism_and_biological_effects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003986183710477 DB - PRIME DP - Unbound Medicine ER -