[Stimulatory response to the oxidation of benzidine and other xenobiotics mediated by lipoxygenase in the presence of phenothiazines].
OBJECTIVE
To test the possibility that certain efficient substrates for lipoxygenase (LOX) produce shuttle oxidants that stimulate the generation of reactive oxygen species from other chemicals.


METHODS
Metabolic interactions were conducted in vitro between chlorpromazine (BZ) or other phenothiazines and benzidine or other xenobiotics mediated by soybean lipoxygenase (SLO) or purified human term placental lipoxygenase (HTPLO) in the presence of hydrogen peroxide, and the rates of xenobiotics oxidation were measured by spectroscopic analysis.


RESULTS
Chlorpromazine cation radical (CPZ(*+)) generated by lipoxygenase triggered a rapid oxidation of benzidine to benzidine diimine cation. Under the experimental conditions used, the metabolic interaction resulted in a 42-fold greater stimulation than BZ alone in the rate of BZ oxidation. The magnitude of stimulation of benzidine oxidation exhibited a dependence on the pH of the reaction medium, amount of the enzyme, and concentration of chlorpromazine, BZ, and hydrogen peroxide. A number of other phenothiazines were also found to stimulate BZ oxidation, albeit to a lesser degree. Chlorpromazine cation radical stimulated the oxidation of all six other xenobiotics tested. The highest stimulation (94-fold) was noted in the oxidation of tetramethyl phenylenediamine to Wursters blue radical, while the lowest stimulatory response (2-fold) was observed in guaiacol. Preliminary data showed that purified HTPLO also displayed a similar stimulatory response to benzidine oxidation in the presence of chlorpromazine.


CONCLUSIONS
Both soybean lipoxygenase and purified human term placental lipoxygenase can mediate stimulatory response to the oxidation of benzidine and other xenobiotics in the presence of phenothiazines.
Hu
Jian-an
JA
Department of Occupational Health and Environmental Health, School of Public Health, Central North University, Changsha 410078, China.
Wu
Yue
Y
Kulkarni
Aron P
AP
D001560:Benzidines / Q000378:metabolism*; D002746:Chlorpromazine / Q000737:chemistry; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008084:Lipoxygenase / Q000302:isolation & purification / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010640:Phenothiazines / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D015262:Xenobiotics / Q000378:metabolism
D001560:Benzidines; D010640:Phenothiazines; D015262:Xenobiotics; C029876:benzidine; D008084:Lipoxygenase; D002746:Chlorpromazine