Biotransformation of para-aminobenzoic acid and salicylic acid by PMN.
Para-aminobenzoic acid (PABA) is an essential cofactor for the production of folic acid in bacteria and has mild anti-inflammatory activity. We have recently reported that salicylic acid and benzoic acid are oxidized by stimulated granulocytes Polymorphonuclear Neutrophils (PMN). The oxidation of salicylate appears mediated by a potent oxygen metabolite generated during the respiratory burst which is dependent primarily on superoxide (O2-) for its production. These background studies with the salicylate group of drugs suggested that PABA might be similarly metabolized by PMN. In these studies, we demonstrate that PABA is metabolized by stimulated PMN. However, in contrast to the biochemical mechanism involved in the metabolism of salicylate, our scavenger studies indicate that PABA is metabolized primarily by the myeloperoxidase pathway. Our results may explain the mild anti-inflammatory actions of the drug and suggest that the degradation of PABA by PMN at an inflammatory site may limit the availability of PABA for bacterial growth.
Sagone
A L
AL
Department of Internal Medicine, Ohio State University, Columbus 43210.
Husney
R M
RM
Davis
W B
WB
D010129:4-Aminobenzoic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D003653:Decarboxylation; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012459:Salicylates / Q000378:metabolism / Q000493:pharmacokinetics*; D020156:Salicylic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D012459:Salicylates; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; D020156:Salicylic Acid; D010129:4-Aminobenzoic Acid