Effect of nephrotic syndrome on homocysteine metabolism
Autor: | Nosratola D. Vaziri, Pavan Gollapudi, Mohammad A. Aminzadeh |
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Rok vydání: | 2010 |
Předmět: |
Male
medicine.medical_specialty Hyperhomocysteinemia Nephrotic Syndrome Homocysteine Blotting Western Hypercholesterolemia Cystathionine beta-Synthase Renal function Rats Sprague-Dawley Excretion chemistry.chemical_compound Internal medicine Animals Medicine Methylenetetrahydrofolate Reductase (NADPH2) Transplantation Proteinuria biology business.industry Albumin medicine.disease Cystathionine beta synthase Rats Endocrinology chemistry Nephrology biology.protein medicine.symptom business Nephrotic syndrome |
Zdroj: | Nephrology Dialysis Transplantation. 26:1244-1247 |
ISSN: | 1460-2385 0931-0509 |
DOI: | 10.1093/ndt/gfq551 |
Popis: | Background. Proteinuria and hyperhomocysteinaemia are independently associated with increased risk of atherosclerosis and cardiovascular disease. The available data on plasma homocysteine (Hcy) level in patients with nephrotic syndrome (NS) are contradictory with increased, decreased and unchanged values reported by different investigators. The majority of Hcy in the plasma is bound to albumin whose urinary losses and diminished plasma concentration are the defining features of NS. The present study was designed to explore the effect of NS on plasma concentration and urinary excretion of Hcy and hepatic expression of methylenetetrahydrofolate reductase (MTHFR) and cystathionine-β-synthase (CBS), the key enzymes in remethylation and trans-sulphuration of Hcy, respectively. Methods.Sprague–DawleyratswererenderednephroticbyIP injection of puromycin aminonucleoside. Urine and plasma were used for measurement of Hcy, and the liver was processed for assessment of MTHFR and CBS protein expression. Results. Compared with the controls, nephrotic rats showed heavy proteinuria, hypoalbuminaemia, hypercholesterolaemia, normal plasma creatinine and creatinine clearance, reduced plasma Hcy, increased urinary Hcy, and downregulation of CBS but not MTHFR expression. Plasma Hcy correlated directly with plasma albumin and inversely with urinary protein excretion. The urinary Hcy excretion correlated directly with urine protein excretion. Conclusions. NS results in significant reduction in plasma total Hcy concentration which is due to the reduction in albumin-bound Hcy as opposed to the free Hcy fraction. This is coupled with increased urinary excretion of albuminbound Hcy. In addition, NS results in down-regulation of CBS which can curtail conversion of Hcy to cysteine and reduce production of H2S which is an important endogenous signalling molecule. |
Databáze: | OpenAIRE |
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