Isoniazid-mediated irreversible inhibition of the myeloperoxidase antimicrobial system of the human neutrophil and the effect of thyronines

Mechanism-Based Inhibition of Myeloperoxidase by Hydrogen Peroxide: Enhancement of Inactivation Rate by Organic Donor Substrates

“…The presence of the hydrazide, ISD or HDL, greatly accelerated the inactivation process. This finding is consistent with earlier studies on MPO inactivation [8,10,20] where the rates and extents of inactivation were markedly stimulated by the presence of a reductant substrate capable of generating inactivating intermediates or products.…”

“…In this study, we have used a steady state kinetics approach to demonstrate that MPO is irreversibly inactivated by excess H 2 O 2 in the absence of reducing substrate. The rate of the inactivation process is enhanced in the presence of suicide substrates, isoniazid (ISD) and hydralazine (HDL), which are known inactivators of the enzyme [10,11]. We also describe a novel bimolecular rate constant that formally describes the activating effect of a suicide donor substrate on hydroperoxideinitiated inactivation of peroxidases.…”

Horseradish Peroxidase-Catalyzed Oxidation of Rifampicin: Reaction Rate Enhancement by Co-oxidation with Anti-inflammatory Drugs

“…Dipyrone has been described as a thyroid peroxidase and lactoperoxidase inhibitor 24) and isoniazid, piroxicam and diclofenac as inhibitors of myeloperoxidase. 25,26) Among the drugs tested here, only diclofenac was able to inhibit significantly the oxidation of rifampicin, suggesting that diclofenac is the best inhibitor in this experimental model. Chart 2 depicts the proposed mechanism for the oxidation of rifampicin and the role of paracetamol as a co-substrate.…”

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

“…Ampicillin has also been reported to act as an electron donor and/or superoxide generator (384). Dapsone and isoniazid directly interfere with MPO and impair the production of HOCl by the MPO-H 2 O 2 -halide system: dapsone converts MPO into its inactive (ferryl) form (394), while isoniazid serves as a suicide substrate for MPO (395). Cefdinir, a hydroxy-imino-aminothiazolyl cephalosporin, impairs MPO activity in the external medium but not in the phagolysosome, probably because it does not enter neutrophils (215).…”