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

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 (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.

Palm tocotrienol-rich fraction inhibits methionine-induced cystathionine β-synthase in rat liver

“…It also reduced methionine-induced oxidative stress in the aorta and heart [30,31]. The ability of folate to reduce oxidative stress was recently reported elsewhere [18,36].…”

Selective homocysteine lowering gene transfer attenuates the development of pressure overload-induced cardiomyopathy in mice

“…Handy et al [34] previously demonstrated that homocysteine decreases glutathione peroxidase activity by altering the specific translational mechanism essential for the synthesis of this selenocysteine-containing protein. Superoxide dismutase protein levels in the heart were reduced in a dog model [35] and in a rat model of chronic hyperhomocysteinemia [36]. Production of reactive oxygen species is increased by hyperhomocysteinemia.…”

Effects of Acute Administration of D,L-Homocysteine Thiolactone on the Antioxidative Status of Rat Intestine and Liver

“…Kolling et al [17] showed that Hcy increased lipid peroxidation and TBARS level in rats' heart. Lipid peroxidation was also observed in the liver of rats, and was associated with Hcyinduced cell injury, including apoptosis and infl ammation in liver disease [12,13].…”