Glutathione Conjugates of Hydralazine Formed in Theperoxidase/Hydrogen Peroxide/Glutathione System
The antihypertensive drug hydralazine is associated withthe induction of symptoms similar to systemic lupuserythematosus (Perry, 1973); it is also associated withlung tumors in mice (Toth, 1978), is mutagenic inseveral short term bacterial and mammalian cell assays (Williams et. al., 1980) and results in the irreversible inactivation of several amine oxidases (Lyles et. al., 1983, Numata et. al., 1981). Mechanisms responsible forthese conditions are unknown.
KeywordsAmine Oxidase Iodoacetic Acid Glutathione Conjugate Standard Reaction Mixture Thiyl Radical
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- Lyles, G.A., Garcia-Rodriguez, J., and Callingham, B.A. (1983). Inhibitory actions of hydralazine upon monoamine oxidizing enzymes in the rat. Biochem. Pharmacol. 32, 2515–2521.Google Scholar
- O’Brien, P.J. (1988). Radical formation during the peroxidase catalyzed metabolism of carcinogens and xenobiotics: the reactivity of these radicals with GSH, DNA and unsaturated lipid. Free Rad. Biol. Med. 4, 169–183.Google Scholar
- Reed, D.J., Babson, J.R., Beatty, P.W., Brodie, A.E.,Ellis, W.W., and Potter, D.W. (1980). High performance liquid chromatographic analysis of nanomole levels of glutathione disulfide and related thiols. Anal. Biochem. 106, 55–62.Google Scholar
- Sinha, B.K. (1983). Enzymatic activation of hydrazinederivatives. A spin trapping study. J. Biol. Chem. 258, 786–801.Google Scholar
- Streeter, A.J., and Timbre’’, J.A. (1985). Enzyme mediated covalent binding of hydralazine to rat liver microsomes. Drug Metab. Dispos. 13, 255–259.Google Scholar
- Toth, B. (1978). Tumorigenic effect of 1-hydrazinophthalazine hydrochloride in mice. J. Natl.Cancer Inst. 61, 1363–1365.Google Scholar