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

Laboratório de Neuroproteção e Doenças Metabólicas, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, CEP, Porto Alegre, RS, Brazil.
Cardiovascular toxicology (Impact Factor: 1.72). 11/2010; 11(1):67-73. DOI: 10.1007/s12012-010-9094-7
Source: PubMed


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 (H(2)DCF) 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.

1 Follower
7 Reads
  • Source
    • "High plasma Hcy concentrations may increase in different pathophysiological conditions (renal failure, rheumatoid arthritis and B-vitamins deficiencies etc.), which is considered as a risk factor for cardiovascular diseases (Linnebank et al., 2011; Mahalle et al., 2013). Regarding these possible mechanisms, different pharmacological agents have been evaluated for the prevention of hHcy in many trials (Noll et al., 2009; Yang et al., 2010; Kolling et al., 2011; Liu et al., 2013). The elevation of plasma Hcy levels may contribute to ischemic changes and oxidative stress. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the protective effect of vitamin C towards hyperhomocysteinemia (hHcy) induced oxidative DNA damage using the comet assay. The increase in plasma homocysteine levels is an important risk factor for vascular and cardiovascular diseases through free radical production. This study was also conducted to investigate the histopathological changes in the thoracic aorta and the oxidant/antioxidant status in heart, liver and kidney tissues. Twenty-four adult male Wistar rats were divided as control, hHcy and hHcy + vitamin C group. Chronic hHcy was induced by oral administration of l-methionine (1 g/kg/day) for 28 days. Vitamin C was given 150 mg/kg/day within the specified days. DNA damage was measured by use of the comet assay in lymphocytes. Levels of malondialdehyde (MDA) and glutathione (GSH) as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in heart, liver and renal tissues. Results show that l-methionine administration significantly increased % Tail DNA and Mean Tail Moment in hHcy group as compared with other groups. Vitamin C treatment significantly decreased the high MDA levels and increased activity of antioxidant enzymes in tissues. Aortic diameter and thickness of aortic elastic laminae were significantly lower in hHcy + vitamin C group. Comet assay can be used for the assessment of primary DNA damage caused by hHcy. Histopathological findings showed that vitamin C may have a preventive effect in alleviating the negative effects of hHcy. Vitamin C might be useful in the prevention of endothelial dysfunction caused by hHcy.
    Experimental and Toxicologic Pathology 12/2014; 66(9-10). DOI:10.1016/j.etp.2014.06.004 · 1.86 Impact Factor
  • Source
    • "Thus, the relationship between HCY and observed hsTnT may merely imply the association between the underlying subclinical coronary atherosclerosis and heart failure with minimal myocardial damage. The supplementation of folic acid can be used as an adjuvant therapy in cardiovascular alterations caused by homocysteine.20 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Homocysteine (HCY) is associated with an increased risk for cardiovascular disease, possibly leading to myocardial damage. Cardiac troponin T (TnT), a marker of cardiomyocyte injury, can be detected by high-sensitivity TnT (hsTnT) assay. The current study investigated the relationship between plasma HCY and hsTnT levels in a community-based population. We related plasma levels of hsTnT to HCY levels in 1,497 participants (mean age, 62.4 years; 629 men, 868 women) from a community-based population in Beijing, People's Republic of China. In multiple logistic regression models, serum HCY was associated with a higher likelihood of detectable hsTnT (odds ratio 1.5; 95% confidence interval 1.07-2.10; P=0.018). A subsequent subgroup analysis found that in subjects aged 65 years and older, the association between hsTnT levels and HCY levels was strengthened. The association between hsTnT and HCY was not present in the younger subgroup (<65 years old). Levels of serum HCY are associated with hsTnT levels in the elderly, indicating a relationship between HCY and subclinical myocardial damage.
    Clinical Interventions in Aging 01/2014; 9:79-84. DOI:10.2147/CIA.S56054 · 2.08 Impact Factor
  • Source
    • "Oxidant injury has been suggested as a potential mechanism of atherogenesis in hyperhomocysteinemia (Sauls et al., 2007). Results of Kolling et al. (2011) demonstrated that supplementation of folic acid can be used as an adjuvant therapy in cardiovascular alterations caused by Hcy. They observed that Hcy induced oxidative-nitrative stress in a rat heart while folic acid had protective properties. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Elevated concentration of homocysteine (Hcy) in human tissues, definied as hyperhomocysteinemia has been correlated with some diseases, such as cardiovascular, neurodegenerative, and kidney disorders. Homocysteine occurs in human blood plasma in several forms, including the most reactive one, the homocysteine thiolactone (HTL) - a cyclic thioester, which represents up to 0.29% of total plasma Hcy. In the article, the effects of hyperhomocysteinemia on the complex process of hemostasis, which regulates the flowing properties of blood, are described. Possible interactions of homocysteine and its different derivatives, including homocysteine thiolactone, with the major components of hemostasis such as endothelial cells, blood platelets, plasmatic fibrinogen and plasminogen, are also discussed. Modifications of hemostatic proteins (N-homocysteinylation or S-homocysteinylation) induced by Hcy or its thiolactone seem to be the main cause of homocysteine biotoxicity in hemostatic abnormalities. It is suggested that Hcy and HTL may also act as oxidants, but various polyphenolic antioxidants are able to inhibit the oxidative damage induced by Hcy or HTL. We also discuss the role of phenolic antioxidants in hyperhomocysteinemia -induced changes in hemostasis.
    Acta biochimica Polonica 05/2012; 59(2):185-94. · 1.15 Impact Factor
Show more