RENAL CORTICAL MITOCHONDRIAL INTEGRITY IN EXPERIMENTAL CYCLOSPORINE NEPHROTOXICITY

Publisher Website
Google Scholar
Abstract
The function of renal cortical mitochondria isolated from rats with cyclosporine nephrotoxicity was studied. Renal cortical mitochondria were isolated from 5 male Fischer rats after 14 days of daily intraperitoneal administration of CsA, 25 mg/kg body wt. Compared with the mitochondrial function of 5 pair-fed control rats receiving vehicle alone, state 3 respiration (ADP-dependent) using several substrates was midly depressed only with pyruvate-malate supported respiration (27 .+-. 3 vs. 36 .+-. 2 nmol O2/min/mg protein; P < 0.05). The Ca2+ accumulation rate was slightly reduced (354 .+-. 14 vs. 416 .+-. 18 nmol/min/mg protein; P < 0.025) while the cytochrome enzyme concentrations were not different from controls. Respiratory control ratios were not affected (CsA group: 9.5 .+-. 2.8, control group: 8.9 .+-. 2.3; glutamate-malate as substrates). These minor alterations in mitochondrial function occurred in the presence of severe depression in the glomerular filtration rate and renal morphologic changes commonly seen with CsA adminstration. Moreover, there was no increase in enzymura. These results indicate that CsA has minor effects on the respiratory function of renal cortical mitochondira. The severe depression in the glomerular filtration rate is out of proportion to these minor alterations in mitochondrial function. These finding argue against a prominent role for a direct toxic action of CsA on tubular cells in the pathogenesis of acute cyclosporine-induced renal dysfunction.