PMID: 9436263Jan 1, 1997Paper

Oxidation of phenothiazines by human term placental peroxidase in non-smokers

Teratogenesis, Carcinogenesis, and Mutagenesis
X Yang, A P Kulkarni

Abstract

Several phenothiazine derivatives have been shown to cause reproductive toxicity. The biochemical mechanisms responsible for these effects are not fully understood at present. In this study, we investigated hydrogen peroxide-dependent oxidation of seven phenothiazines by purified human term placental peroxidase. Promazine was employed as the prototype phenothiazine drug. Promazine was easily oxidized to a cation radical (absorption maximum at 513 nm) when incubated under acidic conditions with human term placental peroxidase in the presence of hydrogen peroxide. The rate of the radical formation was 350 +/- 30 nmol/min/mg protein when 30 micrograms of the purified peroxidase was incubated with 10 mM promazine and 1.0 mM hydrogen peroxide in acetate buffer pH 3.5. The reaction was linear with respect to time, exhibited dependence on the amount of enzyme, and the concentration of promazine and hydrogen peroxide. Collectively, the results suggest an enzymatic nature of the reaction. Reduced glutathione, ascorbate, and NADH suppressed the rate of promazine radical formation presumably by its reduction back to promazine in a concentration-dependent manner. Concomitantly, NADH was co-oxidized. The cation radical formation and NADH ox...Continue Reading

Citations

Dec 21, 2004·Chemico-biological Interactions·Mohammad A EghbalPeter J O'Brien
Jun 3, 2009·Basic & Clinical Pharmacology & Toxicology·Cristiane L Dalla CorteJoão B T Rocha

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