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Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats

Published online by Cambridge University Press:  08 March 2007

Nieves Díez ,
Raquel Pérez ,
Verónica Hurtado  and
Santiago Santidrián
Nieves Díez
Affiliation:
Department of Human Physiology, School of Medicine, University of Navarra, 31080 Pamplona, Spain
Raquel Pérez
Affiliation:
Department of Human Physiology, School of Medicine, University of Navarra, 31080 Pamplona, Spain
Verónica Hurtado
Affiliation:
Laboratory of Thrombosis and Hemostasia, School of Medicine, University of Navarra, 31080 Pamplona, Spain
Santiago Santidrián*
Affiliation:
Department of Human Physiology, School of Medicine, University of Navarra, 31080 Pamplona, Spain
*
*Corresponding author: Dr S. Santidrián, fax +34 48 425649, email [email protected]
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Abstract

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Diet is the most common cause of mild hyperhomocysteinaemia (HHcy), which occurs in approximately 5–7 % of the general population. Since HHcy causes endothelial damage by oxidative stress in different organs, the present study was designed to examine whether HHcy might be involved in renal oxidative stress. Twenty-five male Wistar rats were randomly divided into two groups: one (n 13) was fed ad libitum a folate-free diet (FF) and the other (n 12) was fed the same diet supplemented with folic acid (control, CO). After 8 weeks the animals were killed and kidneys removed. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in plasma and kidney homogenates. Renal tissue sections were analysed by indirect immunostaining with the primary antibody against oxidatively modified LDL receptor (LOX-1). A marked HHcy was confirmed in the FF group. As compared with CO animals, MDA levels in plasma and kidney homogenate were significantly higher in FF rats (P<0·05). Similarly, renal GPx and SOD activities were significantly higher in the FF group (P<0·001). No differences were found in LOX-1 immunohistochemical expression, which in the two groups was displayed in tubular cells. The present study provides evidence that HHcy does produce renal oxidative stress mediated by lipid peroxidation, and that the increased kidney MDA displayed by FF animals may enhance kidney antioxidant activity and thereby attenuate both kidney damage and expression of LOX-1.

Keywords

HomocysteineFolic acidOxidative stressKidney
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 2 , August 2005 , pp. 204 - 210
Copyright
Copyright © The Nutrition Society 2005

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