maleic-acid and Kidney-Diseases

Maleic acid (MA)-induced nephropathy that is characterized by proteinuria, glycosuria, phosphaturia and a deficient urinary acidification and concentration. Sulforaphane (SF) is an indirect antioxidant that shows nephroprotective effects. The aim of the present work was to test the pre-treatment with SF against the MA-induced nephropathy. Wistar rats (230-260 g) were separated in the following groups: control, MA (which received 400 mg/kg of MA), SF + MA (which received MA and 1 mg/kg of SF each day for four days) and SF (which only received SF). MA induced proteinuria, an increase in urinary excretion of N-acetyl-β-d-glucosaminidase, and a decrease in plasma glutathione peroxidase activity, renal blood flow, and oxygenation and perfusion of renal cortex. All these impairments correlated with higher levels of oxidative damage markers and exacerbated superoxide anion production on renal cortex. Moreover, MA impaired mitochondrial bioenergetics associated to complex I, mitochondrial membrane potential and respiratory control index and increased the mitochondrial production of hydrogen peroxide. Further it disrupted mitochondrial morphology. SF prevented all the above-described alterations. In conclusion, the protective effect of SF against MA-induced nephropathy is associated with preservation of mitochondrial bioenergetics, amelioration of oxidative stress and improvement of renal hemodynamics and renal cortex oxygenation.

Topics: Animals; Energy Metabolism; Hemodynamics; Humans; Isothiocyanates; Kidney; Kidney Diseases; Male; Maleates; Mitochondria; Oxidative Stress; Plant Extracts; Rats, Wistar; Reactive Oxygen Species; Sulfoxides

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

Topics: Aldehyde Reductase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Biomarkers; Blotting, Western; Curcumin; Electron Transport Complex I; Enzyme Inhibitors; Hemodynamics; Kidney Diseases; Lipid Peroxidation; LLC-PK1 Cells; Male; Maleates; Mitochondria; Oxidation-Reduction; Oxidative Stress; Oxygen Consumption; Rats; Rats, Wistar; Reactive Oxygen Species; Swine

The present study was designed to evaluate the relationship between renal lipid peroxidation and acute renal damage induced by six nephrotoxic compounds: mercuric chloride (MC), glycerol (GL), maleic acid (MA), cephaloridine (CER), gentamicin (GM) and cisplatin (CDDP) in rats. Urine and blood biochemical analyses, determination of renal lipid peroxidation and its scavengers, and histopathological examination were performed in the time or day course after a single dose, or during consecutive administration of these compounds. Moreover, the effects of the antioxidant N,N'-diphenyl-p-phenylene-diamine (DPPD) on the renal damage induced by each compound were studied. 1. MC was administered subcutaneously once at doses of 2 or 4 mg/kg. At a dose of 4 mg/kg, the increase of renal malondialdehyde (MDA) as an index of lipid peroxidation was observed 12 hours after administration. The increase of renal MDA was associated with the development of mild necrosis in proximal straight tubules (PST). Pretreatment of rats with DPPD 600 mg/kg, i.p. ameliorated MC-induced nephrotoxicity. These results indicate that lipid peroxidation plays a significant role in MC-induced renal damage. 2. GL was administered subcutaneously once at doses of 2.5 or 5.0 ml/kg. The increase of MDA was observed on and after 24 hours at a dose of 2.5 ml/kg, 12 hours at a dose of 5.0 ml/kg. These changes were associated with the development of mild necrosis in proximal convoluted tubules (PCT). Pretreatment of rats with DPPD ameliorated GL-induced nephrotoxicity. These results indicate that lipid peroxidation plays a significant role in GL-induced renal damage. 3. MA was administered intraperitoneally once at doses of 100 and 200 mg/kg. Renal MDA did not increase at any observation times. At both doses, vacuole formation, mitochondrial swelling and condensation in PCT were observed 3 hours, and tubular necrosis occurred 3 and 6 hours after administration, which were associated with a decrease of renal glutathione. Pretreatment of rats with DPPD did not ameliorate MA-induced nephrotoxicity. These results suggest that lipid peroxidation does not play a significant role in MA-induced renal damage. 4. CER was administered intravenously once at doses of 500 and 1000 mg/kg. Renal MDA did not increased at any observation times. At both doses, vacuole formation and mitochondrial swelling in PCT were observed 1 hour, and mild necrosis in PCT was induced 6 hours after administration. On the other hand, DPPD

Topics: Animals; Antioxidants; Cephaloridine; Cisplatin; Gentamicins; Glycerol; Humans; Kidney; Kidney Diseases; Lipid Peroxidation; Maleates; Malondialdehyde; Mercuric Chloride; Phenylenediamines; Rats; Rats, Wistar

A controversy presently exists concerning the ability of albumin to inhibit the tubular reabsorption of low-molecular-weight (M(r)) proteins in experimental renal diseases leading to massive proteinuria. We have examined the urinary excretion of albumin and of 2 low-M(r) proteins, beta 2-microglobulin and cystatin C, in rats treated with toxins affecting primarily the glomerulus (puromycin amino-nucleoside and Adriamycin) or the tubule (mercuric chloride and maleic acid). Above a threshold of 100 mg/24 h, albuminuria induced by puromycin aminonucleoside (50 mg/kg) and Adriamycin (5 mg/kg) was associated with a marked increase in the urinary excretion of beta 2-microglobulin and cystatin C peaking at more than 100-fold the baseline levels. These glomerulotoxins did not affect the urinary excretion of the tubular enzyme N-acetyl-beta-D-glucosaminidase. This pattern of effects was completely different from that induced by mercuric chloride (2 mg/kg) and maleic acid (400 mg/kg) which increased the excretion of both N-acetyl-beta-D-glucosaminidase and low-M(r) proteins in rats with albuminuria values below 100 mg/24 h. These results strongly support the hypothesis that at high filtered loads, albumin decreases the tubular uptake of low-M(r) proteins most likely by competition for a common transport mechanism.

Topics: Acetylglucosaminidase; Albumins; Animals; beta 2-Microglobulin; Binding, Competitive; Biological Transport, Active; Cystatin C; Cystatins; Doxorubicin; Kidney Diseases; Kidney Tubules; Male; Maleates; Mercuric Chloride; Molecular Weight; Proteins; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Sprague-Dawley

During the acute renal tubular dysfunction of Fanconi syndrome and type 2 renal tubular acidosis (FS/RTA2) induced by maleic acid in the unanesthetized dog, we observed: 30 minutes after the onset of FS/RTA2, the urinary excretion of lysosomal enzymes, N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (beta-gluc) and beta-galactosidase (beta-galac), increased simultaneously with the anticipated increase in renal clearance of lysozyme; the severities of all these hyperenzymurias increased rapidly, progressively, and in parallel, all reaching a peak some 60 to 80 minutes after their onset; thereafter, while the FS/RTA2 continued undiminished in severity, the severity of the hyperenzymurias decreased rapidly, greatly, progressively, and in parallel; and sodium phosphate loading strikingly attenuated the FS/RTA2 and the hyperenzymurias. Thus, the maleic acid-induced FS/RTA2 is attended by an acute reversible-complex derangement in the renal tubular processing of proteins that: affects not only lysozyme which is normally filtered, but also NAG and other lysosomal enzymes, which are not; and is to some extent functionally separable from that of FS/RTA2. The findings suggest that the derangements in renal processing of lysozyme and lysosomal enzymes are linked, and that a phosphate-dependent metabolic abnormality in the proximal tubule can participate in the pathogenesis of both these derangements and the FS/RTA2.

Topics: Acetylglucosaminidase; Acidosis, Renal Tubular; Animals; beta-Galactosidase; Dogs; Fanconi Syndrome; Female; Galactosidases; Glucuronidase; Hexosaminidases; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Maleates; Metabolic Clearance Rate; Muramidase; Phosphates

Topics: Animals; Creatinine; Glycosuria; Kanamycin; Kidney Diseases; Male; Maleates; Metals; Molecular Weight; Proteinuria; Rabbits; Renal Aminoacidurias

Topics: Kidney Diseases; Maleates; Sulfhydryl Compounds