ABSTRACT
The present study investigated the stimulatory effects of iron (or ascorbate) on cyclosporine-induced kidney mitochondrial damage. Damaging effect of 50 muM cyclosporine plus 20 muM Fe2+ on mitochondrial lipids and proteins of rat kidney and hyaluronic acid was greater than the summation of oxidizing action of each compound alone, except sulfhydryl oxidation. Cyclosporine and 100 muM ascorbate showed an enhanced damaging effect on lipids but not on proteins. The peroxidative action of cyclosporine on lipids was enhanced with increasing concentrations of Fe2+. Ferric ion (20 muM) also interacted with cyclosporine to stimulate lipid peroxidation. Damaging action of cyclosporine on mitochondrial lipids was enhanced by ascorbate (100 muM and 1 mM). Iron chelators, DTPA and EDTA, attenuated carbonyl formation induced by cyclosporine plus ascorbate. Cyclosporine (100 muM) and 50 muM Fe2+ (or 100 muM ascorbate) synergistically stimulated degradation of 2- alpha deoxyribose. Cyclosporine (1 to 100 muM) reduced ferric ion in a dose dependent manner, which is much less than ascorbate action. Addition of Fe2+ caused a change in absorbance spectrum of cyclosporine in 230~350 nm of wavelengths. The results show that cyclosporine plus iron (or ascorbate) exerts an enhanced damaging effect on kidney mitochondria. Iron and ascorbate appear to promote the nephrotoxicity induced by cyclosporine.
Subject(s)
Animals , Rats , Chelating Agents , Cyclosporine , Deoxyribose , Edetic Acid , Hyaluronic Acid , Iron , Kidney , Lipid Peroxidation , Mitochondria , Pentetic AcidABSTRACT
Objective:To investigate the role of oxygen free radicals in renal dysfunction in rats with obstructive jaundice and the protective effect of Salvia Miltiorrhiae(SM) on renal mitochondria.Methods:The 54 Wistar rats were randomly divided into three groups:sham-operation control group(group A,n=18),obstructive jaundice group(group B,n=18),SM-treated group(group C,n=18).The model of obstructive jaundice in rats was established by common bile duct ligation(CBDL).In group C SM(5ml/kg?d) was given through abdominal cavity for 21 days.The rats were executed at 7th,14th,and 21th day after operation respectively.The contents of serum BIL,Cr,BUN and the contents of renal mitochondria MDA and cholesterol were determined respectively,and the changes of renal histopathology were observed.Results:The contents of renal mitochondria MDA and cholesterol in group B and group C were markedly higher than group A(P
ABSTRACT
The effect of thyroidectomy (Tx) and subsequent treatment with triiodothyronine (T3) on rat kidney mitochondrial oxidative phosphorylation was examined. Thyroidectomy resulted in lowering of state 3 respiration rates and cytochrome contents. Thyroidectomized animals administered with T3 (20 μg/100 g body wt) resulted in the nonsynchronous stimulation of state 3 respiration rates in kidney mitochondria with glutamate, β-hydroxybutyrate, succinate and ascorbate+TMPD as substrates. Cytochrome contents were also elevated differentially. Increase in the state 4 respiration rates was transient and reversible. However, primary dehydrogenases were not generally altered in the Tx and T3- treated Tx animals. The results thus indicate that the T3-treatment to Tx animals brings about differential and nonsynchronous increase in the respiratory parameters and respiratory chain components of kidney mitochondria.