Expression of apolipoprotein B epitopes in low density lipoproteins of hemodialyzed patients

Reade, Véronique; Tailleux, Anne; Reade, Richard; Harduin, P; Cachera, C; Tacquet, A; Fruchart, Jean‐Charles; Fiévet, Catherine

doi:10.1038/ki.1993.389

Cited by 11 publications

(4 citation statements)

References 36 publications

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“…1) and the protein/antigen ratio and the C50 value of the isolated OxLDL were identical to these of standard OxLDL preparations (Table 3). These data suggested that increased immunoreactivity of OxLDL fractions in plasma of these patients depended indeed on the higher extent of protein modification and not on changes in lipid composition as was previously observed with other antibodies (24). The increased electrophoretic mobility, the increased lysine modification, the increased cholesterol/protein ratio, the decreased levels of arachidonic acid and linoleic acid were very similar to these of oxidatively modified LDL extracted from atherosclerotic le sions (25,26).…”

Section: Discussionsupporting

confidence: 77%

Correlation between Oxidized Low Density Lipoproteins and von Willebrand Factor in Chronic Renal Failure

et al. 1996

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SummaryAn ELISA specific for a wide spectrum of oxidized apo B-100 in OxLDL was developed and applied to blood samples from 27 control subjects, 20 mild chronic renal failure (MCRF) patients, 21 severe chronic renal failure patients on conservative treatment (SCRF) and 56 severe chronic renal failure patients on maintenance hemodialysis (HEMO). Mean levels of OxLDL were 0.59 mg/dl in controls (95% Cl, 0.52-0.66 mg/dl), and were 2.7-fold (p <0.01), 3.1-fold (p <0.001) and 5.4-fold (p <0.001) higher in MCRF, SCRF and HEMO patients, respectively. Levels of von Willebrand factor, a marker of endothelial injury, were 100 percent in controls (95% Cl, 90-110 percent), and were 1.5-fold (p = NS), 1.6-fold (p <0.01) and 2.1-fold (p <0.001) higher in MCRF, SCRF and HEMO patients, respectively. Multiple regression analysis revealed that the extent of renal failure (F = 14; p = 0.0004) accounted for a significant fraction of the variation in OxLDL levels, also after exclusion of patients with evidence of ischemic atherosclerotic disease (F = 21; p = 0.0001). After adjustment for the extent of renal failure, hemodialysis (F = 5.6; p = 0.021) and LDL cholesterol levels (F = 7.1, p = 0.0095) contributed significantly to the variation in OxLDL levels. Whereas the extent of renal failure contributed only marginally to the individual variations in vWF levels (F = 4.1; p = 0.048), these levels correlated significantly with plasma levels of OxLDL (F=26; p=0.0001). In conclusion, atherogenic OxLDL increase progressively during the development of renal failure suggesting that the oxidation of LDL may be associated with endothelial injury and atherogenesis in these patients.

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Section: Discussionsupporting

confidence: 77%

Correlation between Oxidized Low Density Lipoproteins and von Willebrand Factor in Chronic Renal Failure

et al. 1996

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“…Such lipoproteins are easily subject to oxidative modification by the generated free radicals, hindering their recognition by the apo B-E receptors in the liver cell, but taken up rapidly by the kidney. 26 This probably explains the significant accumulation of lipids in the kidney cortices of the cisplatin+spironolactone-induced nephrotic animals, with lower hepatic cholesterol content.…”

Section: Discussionmentioning

confidence: 99%

Effect of spironolactone on cisplatininduced nephrotoxicity in rabbits

2001

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The effects of a single interaperitoneal dose of cisplatin (6.5 mg kg day 1), oral doses of spironolactone (20.0 mg kg 1) for 5 days or the combined treatment (spironolactone+cisplatin) on the kidney function and liver function parameters, as well as the serum, liver and kidney cortical lipid contents were studied. The serum urea and creatinine concentrations (measured as kidney function parameters) were not altered by spironolactone treatment, but were significantly (P<0.001) elevated by cisplatin administration. However, animals exposed to both spironolactone+ cisplatin revealed drastic increases in the serum creatinine and urea concentrations amounting to about four and twofold those of cisplatin-alone treated animals, respectively. The histological examination of slides of kidneys from animals exposed to the combined drugs exhibited more extensive necrosis in the tubules compared to those from animals treated with cisplatin alone. Non of the drug treatments had any effects on the serum alanine transaminase (ALT) and aspartate transaminase (AST) levels (measured as liver function parameters) or liver protein content or hepatic alkaline phosphatase (ALP) activity. The histological examination also revealed apparently normal livers in all experimental groups. The cisplatin-induced nephrotoxicity was accompanied by hypercholesterolaemia and hyperphospholipidaemia, whereas spiro nolactone showed a hypocholesterolaemic effect. The concomitant treatment with both cisplatin and spiro nolactone significantly (P<0.05) raised the serum triacylglycerol (TAG) concentration compared to the cisplatin-alone-treated group. Both spironolactone and cisplatin administered separately or jointly caused accumulation of cholesterol and TAG in the kidney cortex with significant depletion of the liver cholesterol content. The present results indicated that spironolactone aggravates the cisplatin-induced nephrotoxicity in the rabbit.

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“…32 LDL, modi®ed by its oxidation, was also suggested to contribute in the dyslipidaemia and progression of glomerulosclerosis. The modi®ed LDL was less effectively recognized by the B/E receptor of the cell for its uptake, 33 but rapidly taken up by macrophages to generate foam cells which play an important pathogenic role in focal segmental glomerulosclerosis and atherosclerosis. 34 Oxidation of LDL can occur as a consequence of lipid peroxidation caused by increased free radical production as demonstrated in uraemic patients, 35 and in drug-induced nephrotic animals.…”

Section: Discussionmentioning

confidence: 99%

Hyperlipidaemia in cisplatin-induced nephrotic rats

Abdel-Gayoum¹,

El-Jenjan²,

Ghwarsha

1999

Hum Exp Toxicol

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1 The serum and hepatic lipid concentrations were investigated in rats made nephrotic with a single intraperitoneal injection of cisplatin (6 mg kg-1 b.wt.). 2 The serum creatinine and urea concentrations were estimated as indices of nephrotoxicity, and the serum total bilirubin level as a liver function test. 3 The fasting serum total cholesterol, triglycerides (TG) and the cholesterol fractions associated with the various lipoproteins, as well as hepatic cholesterol and TG contents were also measured, following 5, 10 and 15 days from the cisplatin treatment. 4 The results revealed that on day 5 both serum creatinine and urea concentrations were significantly (P50.01) increased, indicating the peak of nephrotoxicity, with no injurious effects on the liver as indicated by the unaltered serum bilirubin concentration. 5 The nephrotoxicity was accompanied by significant elevations in serum total cholesterol and TG concentrations by 49 and 42%, respectively, with significant (P50.05) correlations between the serum cholesterol and TG concentrations versus the serum urea (r=0.68 and r=0.60, respectively). 6 Among the estimated lipoproteins, very low density lipoprotein (VLDL) cholesterol was severely increased to more than twofold with no severe changes in LDL or HDL-cholesterol fractions. On day 5 the liver also showed significant accumulation of TG with no change in the cholesterol content. 7 Animals killed 10 or 15 days post-cisplatin treatment had all the perturbed parameters returned to the normal levels. 8 The present results indicated that rats exposed to a single cisplatin injection exhibit acute reversible nephrosis on day 5 which was accompanied by dyslipidaemia and accumulated liver TG.

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Expression of apolipoprotein B epitopes in low density lipoproteins of hemodialyzed patients

Cited by 11 publications

References 36 publications

Correlation between Oxidized Low Density Lipoproteins and von Willebrand Factor in Chronic Renal Failure

Correlation between Oxidized Low Density Lipoproteins and von Willebrand Factor in Chronic Renal Failure

Effect of spironolactone on cisplatininduced nephrotoxicity in rabbits

Hyperlipidaemia in cisplatin-induced nephrotic rats

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