Cytochrome P-450 as a source of catalytic iron in minimal change nephrotic syndrome in rats.
We have recently demonstrated an important pathogenic role for glomerular catalytic iron in the puromycin aminonucleoside (PAN) induced minimal change nephrotic syndrome (MCNS). The source of this iron capable of catalyzing free radical reactions is not known. We examined the role of cytochrome P-450 (CYP) as a source of catalytic iron in a model MCNS induced by single injection of PAN to rats. Treatment of PAN resulted in a marked increase in the catalytic iron associated with significant loss of glomerular CYP content. Administration of CYP inhibitors significantly prevented the injury-induced loss of CYP content and the increase in the catalytic iron in the glomeruli accompanied by a marked decrease in proteinuria. In an in vitro study utilizing glomerular epithelial cells (GEC), CYP inhibitors also markedly prevented the PAN-induced increase in the catalytic iron and hydroxyl radical formation accompanied by significant protection against PAN-induced cytotoxicity. Taken together our data indicate that the CYP, a group of heme protein, may serve as a significant source of this catalytic iron.
Liu
H
H
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Shah
S V
SV
Baliga
R
R
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011507:Proteinuria; D011692:Puromycin Aminonucleoside; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019459:Urothelium / Q000378:metabolism
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D011692:Puromycin Aminonucleoside; D002927:Cimetidine; D011899:Ranitidine; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D010882:Piperonyl Butoxide