Document Detail


Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney.
MedLine Citation:
PMID:  20980407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) levels, is a metabolic disease. It is a common clinical finding in patients with chronic kidney diseases and occurs almost uniformly in patients with end-stage renal disease. Hyperhomocysteinemia is also a risk factor for cardiovascular disease. Our recent studies indicate that hyperhomocysteinemia can lead to renal injury by inducing oxidative stress. Oxidative stress is one of the important mechanisms contributing to Hcy-induced tissue injury. Folic acid supplementation is regarded as a promising approach for prevention and treatment of cardiovascular disease associated with hyperhomocysteinemia due to its Hcy-lowering effect. However, its effect on the kidney is not clear. The aim of this study was to examine the effect of folic acid supplementation on Hcy-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the kidney during hyperhomocysteinemia. Hyperhomocysteinemia was induced in male Sprague-Dawley rats fed a high-methionine diet for 12 wk with or without folic acid supplementation. A group of rats fed a regular diet was used as control. There was a significant increase in levels of superoxide anions and lipid peroxides in kidneys isolated from hyperhomocysteinemic rats. Activation of NADPH oxidase was responsible for hyperhomocysteinemia-induced oxidative stress in the kidney. Folic acid supplementation effectively antagonized hyperhomocysteinemia-induced oxidative stress via its Hcy-lowering and Hcy-independent effect. In vitro study also showed that 5-methyltetrahydrofolate, an active form of folate, effectively reduced Hcy-induced superoxide anion production via NADPH oxidase. Xanthine oxidase activity was increased and superoxide dismutase (SOD) activity was decreased in the kidney of hyperhomocysteinemic rats, which might also contribute to an elevation of superoxide anion level in the kidney. Folic acid supplementation attenuated xanthine oxidase activity and restored SOD activity in the kidney of hyperhomocysteinemic rats. These results suggest that folic acid supplementation may offer renal protective effect against oxidative stress.
Authors:
Sun-Young Hwang; Yaw L Siow; Kathy K W Au-Yeung; James House; Karmin O
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-27
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  300     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-07     Completed Date:  2011-02-09     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F189-98     Citation Subset:  IM    
Affiliation:
Department of Animal Science, University of Manitoba, and Integrative Biology Laboratory, St. Boniface Hospital Research Centre, 351 Tache Ave., Winnipeg, Manitoba, Canada R2H 2A6.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology
Animals
Cells, Cultured
Folic Acid / therapeutic use*
Humans
Hyperhomocysteinemia / chemically induced,  complications*
Kidney / drug effects*,  metabolism*
Male
Methionine / administration & dosage
NADPH Oxidase / antagonists & inhibitors*
Oxidative Stress
Rats
Rats, Sprague-Dawley
Superoxide Dismutase / metabolism
Superoxides / metabolism*
Xanthine Oxidase / metabolism
Chemical
Reg. No./Substance:
0/Acetophenones; 11062-77-4/Superoxides; 498-02-2/acetovanillone; 59-30-3/Folic Acid; 63-68-3/Methionine; EC 1.15.1.1/Superoxide Dismutase; EC 1.17.3.2/Xanthine Oxidase; EC 1.6.3.1/NADPH Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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