Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E

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Abstract
Cardiovascular diseases are the leading cause of death in haemodialysis patients. Hyperhomocysteinaemia is an independent risk factor. Basic research has provided strong evidence that oxidation of low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Oxidative stress, lipid metabolism alterations, and hyperhomocysteinaemia observed in haemodialysis patients could induce increases in LDL oxidation. This study was designed to determine the effect of folinic acid on hyperhomocysteinaemia and to assess the antioxidant efficacy of folinic acid. The antioxidant effect of folinic acid was compared with that of vitamin E. Sixteen stable patients (11 men, five women; mean age 54.3+/-6.32 years) on standard haemodialysis received 400 mg of vitamin E, orally, at the end of each haemodialysis session for 3 months. After a 1-month wash-out, they received 10 mg of folinic acid, intravenously, at the end of each haemodialysis session for an additional 3 months. Blood samples were drawn in the morning after an overnight fast and before dialysis. Plasma vitamin E was analysed by high-pressure liquid chromatography. Malondialdehyde (MDA) was determined using a fluorimetric method and plasma copper oxidized anti-LDL antibodies (Ab-LDLox) were measured with an ELISA method using native LDL and oxLDL as antigens. Plasma homocysteine was determined by an FPIA method. Folinic acid supplements significantly reduced hyperhomocysteinaemia (-44%), MDA concentrations (-40%), and IgG-LDLox titres (-13%). Treatment with folinic acid lowers plasma homocysteine levels and, like vitamin E, affords antioxidant protection, which prevents lipid peroxidation. This lowering of lipid peroxidation may reduce the risk of atherosclerosis and prevent or delay cardiovascular complications in HD patients.

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