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Homocysteine Induces Oxidative–Nitrative Stress in Heart of Rats: Prevention by Folic Acid

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Abstract

Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and thrombosis; however, the mechanisms by which homocysteine triggers these dysfunctions are not fully understood. In the present study, we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely thiobarbituric acid reactive substances, an index of lipid peroxidation, 2′,7′-dichlorofluorescein (H2DCF) oxidation, activities of antioxidant enzymes named superoxide dismutase and catalase, as well as nitrite levels in heart of young rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3–0.6 μmol/g body weight) and/or folic acid (0.011 μmol/g body weight) from their 6th to the 28th day of life. Controls and treated rats were killed 1 h and/or 12 h after the last injection. Results showed that chronic homocysteine administration increases lipid peroxidation and reactive species production and decreases enzymatic antioxidant defenses and nitrite levels in the heart of young rats killed 1 h, but not 12 h after the last injection of homocysteine. Folic acid concurrent administration prevented homocysteine effects probable by its antioxidant properties. Our data indicate that oxidative stress is elicited by chronic hyperhomocystenemia, a mechanism that may contribute, at least in part, to the cardiovascular alterations characteristic of hyperhomocysteinemic patients. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in cardiovascular alterations caused by homocysteine.

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Acknowledgments

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—Brazil), FINEP Research Grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)-Proc. No. 01.06.0842-00”, and “Instituto Nacional de Ciência e Tecnologia (INCT) para Excitotoxicidade e Neuroproteção (INCT/CNPq)”.

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Correspondence to Angela T. S. Wyse.

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Kolling, J., Scherer, E.B., da Cunha, A.A. et al. Homocysteine Induces Oxidative–Nitrative Stress in Heart of Rats: Prevention by Folic Acid. Cardiovasc Toxicol 11, 67–73 (2011). https://doi.org/10.1007/s12012-010-9094-7

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