Role of oxygen radicals in phorbol myristate acetate-induced glomerular injury.
Phorbol myristate acetate (PMA) is known to be a potent activator of neutrophils and macrophages resulting in the generation of large amounts of oxygen-free radicals by these cells. When injected into the left renal artery of 250 to 300 g male Sprague-Dawley rats, PMA caused significant proteinuria compared to control rats which received normal saline (35.4 +/- 4 mg/24 hr in PMA treated vs. 14.1 +/- 0.9 mg/24 hr in saline control, P less than 0.02). The proteinuria was associated with evidence of glomerular injury. These PMA-induced alterations were not prevented by complement depletion but were prevented by prior depletion of neutrophils. The coinstillation of catalase prevented the development of the proteinuria (catalase + PMA 12.7 +/- 2.3 mg/24 hr vs. PMA alone 38.2 +/- 5.7 mg/24 hr, P less than 0.001) suggesting that H2O2 and/or its metabolites derived from neutrophils were important in the PMA-induced proteinuria. In contrast, superoxide dismutase (SOD) had no effect. We conclude that, following the intra-arterial injection of PMA, neutrophil-derived hydrogen peroxide and/or its metabolic products are capable of causing acute proteinuria in association with morphological alterations in glomeruli of rats.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000502:physiology*; D010704:Phorbols; D011507:Proteinuria / Q000139:chemically induced*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate
D000975:Antioxidants; D005609:Free Radicals; D010704:Phorbols; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen