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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulation of oxalate leads to hyperoxaluria and calcium oxalate nephrolithiasis in man. Since oxalate is a metabolic end product in mammals, the feasibility of its enzymic degradation has been tested in vivo in rats by administering exogenous oxalate oxidase. Oxalate oxidase, isolated from banana fruit peels, in its native form was found to be non-active at the physiological pH of the recipient animal. However, its functional viability in the recipient animal was ensured by its prior binding with ethylenemaleic anhydride, thus shifting its pH activity curve towards the alkaline range. Rats implanted with dialysis membrane capsules containing such immobilized oxalate oxidase in their peritoneal cavities effectively metabolized intraperitoneally injected [14C]oxalate as well as its precursor [14C]glyoxalate. The implantation of capsules containing coentrapped multienzyme preparations of oxalate oxidase, catalase and peroxidase led to a further degradation of administered [14C]oxalate in rats.
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PMID:Degradation of oxalate in rats implanted with immobilized oxalate oxidase. 394 4

Observed loss in body weight gain, increased lipid peroxidation reaction, decreased concentrations of antioxidants, ascorbic acid, alpha-tocopherol and reduced glutathione and antioxidant enzymes, glutathione peroxidase and catalase and increased concentration of hydroperoxides and hydroxyl radicals in vitamin B6 deficient rat liver [J Nutri Biochem, 2 (1991) 245] and kidney [Biochem International, 21 (1991) 599] were nearly normalized on feeding with vitamin E or methionine. Accumulation of oxalate and calcium during vitamin B6 deficiency was abolished by feeding vitamin E or methionine. Calcium oxalate deposition observed in vitamin B6 deficient kidney was completely prevented when fed along with vitamin E or methionine. However the hyperoxaluria and hypercalciuria persisted even after feeding with vitamin E or methionine.
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PMID:Restoration of tissue antioxidants and prevention of renal stone deposition in vitamin B6 deficient rats fed with vitamin E or methionine. 811 61

The cytoprotective activity of alpha-lipoic acid against free radical toxicity, manifested during experimental hyperoxaluria, has been investigated. Glycollate was used as the inducer of oxalate hyperoxaluria in rats. The increase in lipid peroxidation and superoxide dismutase (SOD) activity, associated with a decrease in catalase activity and glutathione (GSH) level, are the salient features observed in tissues of hyperoxaluric rats. Free radical toxicity in the glycollate fed rats is effectively counteracted by lipoic acid administration. Lipoic acid administration brought about a significant decrease in peroxidative levels with an increase in catalase activity and glutathione level. These observations highlight the antioxidant property of alpha-lipoic acid and its cytoprotective action against experimental hyperoxaluria.
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PMID:Effect of DL alpha-lipoic acid on tissue lipid peroxidation and antioxidant systems in normal and glycollate treated rats. 836 80

Oxalate, the most common constituent of kidney stones, is an end product of metabolism that is excreted by the kidney. During excretion, oxalate is transported by a variety of transport systems and accumulates in renal tubular cells. This process has been considered benign; however, recent studies on LLC-PK1 cells suggested that high concentrations of oxalate are toxic, inducing morphological alterations, increases in membrane permeability to vital dyes and loss of cells from the monolayer cultures. The present studies examined the basis for oxalate toxicity, focusing on the possibility that oxalate exposure might increase the production/availability of free radicals in LLC-PK1 cells. Free radical production was monitored in two ways, by monitoring the reduction of nitroblue tetrazolium to a blue reaction product and by following the conversion of dihydrorhodamine 123 (DHR) to its fluorescent derivative, rhodamine 123. Such studies demonstrated that oxalate induces a concentration-dependent increase in dye conversion by a process that is sensitive to free radical scavengers. Specifically, addition of catalase or superoxide dismutase blocked the oxalate-induced changes in dye fluorescence/absorbance. Addition of these free radical scavengers also prevented the oxalate-induced loss of membrane integrity in LLC-PK1 cells. Thus it seems likely that free radicals are responsible for oxalate toxicity. The levels of oxalate that induced toxicity in LLC-PK1 cells (350 microM) was only slightly higher than would be expected to occur in the renal cortex. These considerations suggest that hyperoxaluria may contribute to the progression of renal injury in several forms of renal disease.
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PMID:Oxalate toxicity in LLC-PK1 cells: role of free radicals. 882 25

Peroxisomal disorders are divided into two groups from a clinical point of view. Diseases in the first group, peroxisome-deficient disorders (PDD), Zellweger-like syndrome, and isolated deficiencies of peroxisomal beta-oxidation enzymes, are characterized by common clinical features including psychomotor retardation, hypotonia, hepatic dysfunction and visual disturbance. The second group includes diseases with a unique manifestation, such as X-linked adrenoleukodystrophy, hyperoxaluria type I and rhizomelic chondrodysplasia punctata. We investigated clinical aspects and the genetic basis of PDD, and the significance of peroxisomes in the development of human brain. Neuroradiological and neurophysiological studies revealed that thick cortex, colpocephaly and multifocal spikes were characteristic findings of PDD patients in the early infantile period. Cytogenetic studies elucidated the presence of eleven complementation groups among PDD, indicating the presence of eleven pathogenic genes for PDD. Molecular studies elucidated two of these genes, PAF-1 and PXR-1. Immunohistochemical studies clarified that the catalase-positive neurons appeared in the basal ganglia, thalamus, and cerebellum at 28 weeks of gestation, and in the cortex at 35 weeks. Immunopositive glial cells appeared from the deep to superficial white matter with increasing gestational age. These results suggest the important role of peroxisomes in neuronal maturation and myelinogenesis.
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PMID:Peroxisomal disorders: clinical aspects. 899 63

LLC-PK1 and Madin-Darby canine kidney (MDCK) cells were used to study the role of free radicals in renal epithelial injury during exposure to oxalate ions (Ox) and calcium oxalate monohydrate (COM) crystals. The cell cultures were exposed for 120 or 240 min to 1.0 mmol Ox or 1.0 mmol Ox plus 500 microg/ml of COM crystals averaging 1.0 microm in size. Exposure of both LLC-PK1 and MDCK cells to Ox alone increased the leakage of lactate dehydrogenase, which was further enhanced when cells were exposed to Ox + COM crystals. The release of lactate dehydrogenase from the LLC-PK1 cell line, however, was significantly higher than that from MDCK cells. LLC-PK1 cells also showed a significant increase in malondialdehyde (MDA) content on Ox challenge. MDA content was even higher when LLC-PK1 cells were challenged with Ox + COM crystals. However, in MDCK cells, the elevated MDA content was similar in both treatment groups, suggesting that these cells may be more resistant to the calcium oxalate crystals. Glutathione peroxidase activity was decreased in both LLC-PK1 and MDCK cells. Challenging cells with Ox + COM resulted in decreased catalase activity in LLC-PK1, but increased catalase activity in MDCK cells. Superoxide dismutase activity and reduced glutathione content were not significantly different in either cell type when challenged with Ox or Ox + COM. Previous in vivo animal studies yielded indirect evidence for the increased lipid peroxidation during hyperoxaluria-induced nephrolithiasis. However, in an animal model, it is difficult to separate the effect of Ox from Ox in combination with COM crystals. This study suggests that the injury to renal tubular epithelial cells is accompanied by lipid peroxidation when exposed to Ox. The injury is augmented when COM crystals are included. LLC-PK1 cells are more susceptible to Ox-associated injury than MDCK cells.
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PMID:Cells of proximal and distal tubular origin respond differently to challenges of oxalate and calcium oxalate crystals. 1054 Dec 82

Renal injury is considered as one of the prerequisites for calcium oxalate retention. In order to determine the role of lipid peroxidation related effects for hyperoxaluria, we evaluated the alterations in lipid peroxidation, antioxidants and oxalate synthesizing enzymes in lithogenic rats with response to vitamin E + selenium treatment. In kidney of lithogenic rats, the level of lipid peroxidation and the activities of oxalate synthesizing enzymes were found to be increased whereas the levels/activities of non-enzymatic and enzymatic antioxidants were found to be decreased. The urinary excretion of both oxalate and calcium were significantly elevated. Supplementation of lithogenic rats with vitamin E + selenium decreased the levels of lipid peroxides and the activities of oxalate synthesizing enzymes like glycolic acid oxidase (GAO), lactate dehydrogenase (LDH), xanthine oxidase (XO) with a concomitant increase in the activities of enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and increased levels of non-enzymatic antioxidants like ascorbic acid, alpha-tocopherol and reduced glutathione (GSH). The urinary excretion of oxalate and calcium were normalized. The antioxidants vitamin E + selenium thereby protected from hyperoxaluria.
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PMID:Supplementation of vitamin E and selenium prevents hyperoxaluria in experimental urolithic rats. 1287 11

Under severe hyperoxaluric conditions calcium oxalate crystals often deposit in the renal interstitium and produce localized inflammation. We have proposed that renal epithelial cells exposed to CaOx crystals produce chemoattractants such as monocyte chemoattractant protein-1 (MCP-1). MCP-1 synthesis is mediated by reactive oxygen species (ROS). HK-2 cells of human renal epithelial line were exposed to CaOx crystals for different lengths of time. The culture media was tested for cell injury marker LDH, and subjected to enzyme-linked immunosorbent assay to determine the secretion of MCP-1 protein. Cell expression of MCP-1 was assessed by Western blot analysis. Gene expression was determined by reverse transcriptase-polymerase chain reaction. The data clearly showed that the HK-2 cells express MCP-1 gene and protein. The MCP-1 mRNA expression was increased following exposure to CaOx crystals, which was reduced upon treatment with free radical scavengers, catalase and superoxide dismutase. Results indicate that CaOx crystals strongly induce MCP-1 synthesis and secretion by the HK-2 cells and production is mediated by intracellular ROS production. Based on these and other data, antioxidant therapy and blockade of rennin-angiotensin system may prove beneficial for the prevention of end stage renal disease caused by hyperoxaluria and CaOx crystal deposition.
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PMID:Reactive oxygen species mediated calcium oxalate crystal-induced expression of MCP-1 in HK-2 cells. 1639 73

The assumption of oxidative stress as a mechanism in oxalate induced renal damage suggests that antioxidants might play a beneficial role against oxalate toxicity. An in vivo model was used to investigate the effect of C-phycocyanin (from aquatic micro algae; Spirulina spp.), a known antioxidant, against calcium oxalate urolithiasis. Hyperoxaluria was induced in two of the 4 groups of Wistar albino rats (n = 6 in each) by intraperitoneally injecting sodium oxalate (70 mg/kg body weight). A pretreatment of phycocyanin (100 mg/kg body weight) as a single oral dosage was given, one hour prior to oxalate challenge. An untreated control and drug control (phycocyanin alone) were employed. Phycocyanin administration resulted in a significant improvement (p < 0.001) in the thiol content of renal tissue and RBC lysate via increasing glutathione and reducing malondialdehyde levels in the plasma of oxalate induced rats (p < 0.001), indicating phycocyanin's antioxidant effect on oxalate mediated oxidative stress. Administering phycocyanin after oxalate treatment significantly increased catalase and glucose-6-phosphate dehydrogenase activity (p < 0.001) in RBC lysate suggesting phycocyanin as a free radical quencher. Assessing calcium oxalate crystal retention in renal tissue using polarization microscopy and renal ultrastructure by electron microscopy reveals normal features in phycocyanin-- pretreated groups. Thus the study presents positive pharmacological implications of phycocyanin against oxalate mediated nephronal impairment and warrants further work to tap this potential aquatic resource for its medicinal application.
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PMID:Oxalate mediated nephronal impairment and its inhibition by c-phycocyanin: a study on urolithic rats. 1647 83

The present in-vivo study was to observe the effect of N-acetylcysteine (NAC) on oxalate-induced oxidative stress on rat erythrocytes. A total of 15 Wistar rats were divided into three groups. The control group received normal saline by single intraperitoneal injection. Hyperoxaluria was induced by single intraperitoneal (i.p.) dose of sodium oxalate (70 mg/kg body weight in 0.5 mL saline) to a second group. The third group was administered single i.p. dose of NAC according to 200 mg/kg body weight dissolved in 0.5 mL saline, half an hour after oxalate dose. NAC administration normalized antioxidant enzyme activities (superoxide dismutase and catalase) and reduced malondialdehyde content (indicator of lipid peroxidation) in hyperoxaluric rat's red blood cell (RBC) lysate. NAC administration also resulted in a significant improvement of thiol content in RBC lysate via increasing reduced glutathione content and maintaining its redox status. Oxalate-caused alteration of cholesterol/phospholipid ratio (determining membrane fluidity) was also rebalanced by NAC administration. Further, after NAC administration, electron microscopy showed improved cell morphology presenting its prophylactic properties. Above results indicate that NAC treatment is associated with an increase in plasma antioxidant capacity and a reduction in the susceptibility of erythrocyte membranes to oxidation. Thus, the study presents positive pharmacological implications of NAC against oxalate-mediated impairment of erythrocytes.
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PMID:Oxalate-mediated oxidant-antioxidant imbalance in erythrocytes: role of N-acetylcysteine. 1973 76


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