Role of Cytochrome P-450 (CYP) as a Source of Catalytic Iron in Puromycin Aminonucleoside (PAN) Induced Animal Model of Minimal Change Nephrotic Syndrome (MCNS)

Abstract 1972

We have recently demonstrated an important pathogenic role for glomerular "catalytic" iron in the PAN induced MCNS. However the source of this glomerular "catalytic" iron capable of catalyzing free radical reactions is not known. In the current study we examined the role of CYP as a source of "catalytic" iron in a model of MCNS induced by injection of PAN (7.5 mg/100gm BW) to rats. In the PAN treated rats CYP content in the glomeruli was not detectable and there was a marked increase in the "catalytic" iron as measured by the bleomycin assay. Administration of CYP inhibitors Cimetidine (CM) and Piperonyl butoxide (PB) significantly prevented the injury induced loss of CYP content (Control: 0.08±0.01; PAN+CM: 0.07±0.01; PAN+PB: 0.07±0.02 nmol/mg protein, n= 3-4) as well as the increase in bleomycin detectable iron in the glomeruli accompanied by a significant decrease in proteinuria. (Table)

Table 1 No caption available

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