Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid.
We have previously demonstrated that acute hyperhomocysteinemia induces oxidative stress in rat brain. In the present study, we initially investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative damage, namely total radical-trapping antioxidant potential and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), as well as on DNA damage in parietal cortex and blood of rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of Hcy (0.3-0.6 micromol/g body weight), and/or folic acid (0.011 micromol/g body weight) from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, parietal cortex and total blood was collected. Results showed that chronic homocysteine administration increased DNA damage, evaluated by comet assay, and disrupted antioxidant defenses (enzymatic and non-enzymatic) in parietal cortex and blood/plasma. Folic acid concurrent administration prevented homocysteine effects, possibly by its antioxidant and DNA stability maintenance properties. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in disorders that accumulate homocysteine.
Matté
Cristiane
C
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Mackedanz
Vanize
V
Stefanello
Francieli M
FM
Scherer
Emilene B S
EB
Andreazza
Ana C
AC
Zanotto
Caroline
C
Moro
Angela M
AM
Garcia
Solange C
SC
Gonçalves
Carlos A
CA
Erdtmann
Bernardo
B
Salvador
Mirian
M
Wyse
Angela T S
AT
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000097:blood / Q000378:metabolism; D004247:DNA / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D005492:Folic Acid / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000097:blood / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology / Q000633:toxicity; D020138:Hyperhomocysteinemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015162:Micronucleus Tests; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D006710:Homocysteine; D004247:DNA; D005492:Folic Acid; D002374:Catalase; D005979:Glutathione Peroxidase