Homocysteine oxidative stress

Paran, E. and Engelhard, Y. 2001. Effect of Lyc-O-Mato, standardized tomato extract on blood pressure, serum lipoproteins, plasma homocysteine and oxidative stress markers in grade 1 hypertensive patients. In Proceedings of the 16th Annual Scientific Meeting of the Society of Hypertension , San Francisco, USA. 

Increases in plasma S-AA levels have previously been reported in patients with coronary disease (57). S-AA and plasma intracellular adhesion molecule-1 were elevated in patients with CAD and hyperhomocysteinemia, but only S-AA decreased after vitamin supplementation (35). Homocysteine activates nuclear factor- in endothelial cells, possibly via oxidative stress (58), and increases monocyte chemoattractant protein-1 expression in vascular smooth muscle cells (59). Additionally, it stimulates interleukin-8 expression in human endothelial cultures (60). These inflammatory factors are known to participate in the development of atherosclerosis. Taken together, these reports suggest an association of elevated tHcy and low-grade inflammation in CAD. 

To conclude, hyperhomocysteinemia is associated with oxidative stress, inflammation, endothelial dysfunction, and dysfunction of coagulation in animals and in humans, but vitamin supplementation does not consistently normalize these changes in spite of large reductions in homocysteine. It still remains be seen whether homocysteine per se causes the pathological processes or whether it is simply an innocent bystander. 

Jonasson T, et al. Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease-a prospective randomized study of vitamin supplementation, Clin Chem Lab Med 2005 43(6) 628-634. 

Mujumdar VS, Aru GM, Tyagi SC. 2001. Induction of oxidative stress by homocysteine impairs endothelial function. J Cell Biochem 82 491-500. 

Tyagi N, Sedoris K, Steed M, et al. 2005. Mechanisms of homocysteine-induced oxidative stress. Am J Physiol Heart Circ Physiol 289 H2649-H2656. 

Yeun JY and Kaysen GA, C-reactive protein, oxidative stress, homocysteine, and troponin as inflammatory and metabolic predictors of atherosclerosis in ESRD. Curr Opin Nephrol Hypertens 9(6) 621-30,2000. 

Patients with CKD are at increased risk of cardiovascular disease, independent of the etiology of their kidney disease. While a clearly unique pathogenesis of cardiovascular disease specific to CKD has not been identified, it is known that manifestations of kidney disease are contributory. Risk factors for cardiovascular disease in this population include hemodynamic and metabolic abnormalities, as well as hypertension, dyslipidemia, elevated homocysteine levels, anemia, hyperparathyroidism, malnutrition, and oxidative stress. Hypertension induced by volume expansion and increased systemic vascular resistance increases myocardial work and contributes to development of left ventricular hypertrophy (LVH). Hyperlipidemia may enhance atherogenesis, while some uremic toxins can decrease myocardial contractflity. In addition, uremic toxins can induce pericarditis, a potentially fatal complication. Currently, measures to screen this high-risk population for cardiovascular risk factors are not routine. ... 

Ho PI, Collins SC, Dhitavat S, Ortiz D, AsUine D, Rogers E, Shea TB. Homocysteine potentiates beta-Amyloid neurotoxicity role of oxidative stress. J Neurochem 2001 78 249-253. 

Stobiecka, M., Deeb, J., Hepel, M., 2010. Ligand exchange effects in gold nanoparticle assembly induced by oxidative stress biomarkers homocysteine and cysteine. Biophys. Chem. 146, 98-107. 

Vanzin CS, et al. Experimental evidence of oxidative stress in plasma of homocystinuric patients a possible role for homocysteine. Mol Genet Metab. 2011 104(l-2) 112-7. 

Figure 3.2 Beneficial effects of folic acid on vascular wall. Folic acid circulates in human body as 5-methyltetrahydrofolate (5-MTHF). 5-MTHF lowers circulating homocysteine (Hey) levels, thus reducing systemic oxidative stress and Hcy-induced activation of prothrombotic mechanisms. In addition, vascular 5-MTHF has a favourable effect on intracellular Hey metabolism, attenuating Hcy-induced activation of NADPH oxidase isoforms (NOXs) in the vascular wall. Furthermore vascular 5-MTHF scavenges per se peroxynitrite (ONOO ) radicals in the vascular wall preventing the oxidation of vascular tetrahydrobiopterin (BH4) associated with endothelial nitric oxide synthase (eNOS) uncoupling and diminished vascular nitric oxide (NO) bioavailability. In total through these effects 5-MTHF lowers vascular oxidative and nitrosative stress. Thus by modulating vascular redox, 5-MTHF inhibits activation of proinffammatory pathways which orchestrate vascular wall inflammation and perpetuate endothelial dysfunction and atherogenesis development (unpublished).

Low levels of vitamin Bg may cause hyperhomocysteinaemia since vitamin Bg acts as a cofactor for tra .s-sulfation of cysteine (Siri et al. 1998). There is evidence that an elevated homocysteine level is a risk factor for heart disease and stroke. Endo et al. (2006) reported that vitamin Bg deficiency induced the oxidant stress which accelerates atherosclerosis. They also highlighted that the antioxidant activity of vitamin Bg may suppress the homo-cysteine-induced atherosclerosis. Vitamin Bg levels may be important in the prevention of coronary heart disease intake of vitamin Bg above the current recommended dietary allowance has been shown to be instrumental in the primary prevention of coronary heart disease among women (Rimm et al. 1998). 

Vitamin B12 is an essential coenzyme for the methylation cycle by activating THF. An activated folate is not only a coenzyme for methionine synthase but also plays a pivotal role in one-carbon metabolism it promotes the generation of methionine from homocysteine, which is a cytotoxic sulfur-containing amino acid that can induce DNA strand breakage, oxidative stress and apoptosis. The methylation cycle is very important in the brain and depends on the SAM concentration. 

Low vitamin B12 and folate and hyperhomocysteinemia induce cognitive decline by impaired DNA synthesis, impair genomic and non-genomic methylation, homocysteine-induced DNA synthesis, neurotoxicity and oxidative stress. 

The associations between issues B, C and vitamin B12 are discussed here. Concerning issue A, oxidative stress by free radicals formed during the reducing process of homocysteine is reported to injure endothelial cells directly (Mansoor et al. 1995). 

The toxicity of homocysteine is manifested by the following three reactions are as followed (A) reaction directly inducing oxidative stress ... 

Nolin, T. D., M. E. McMenamin, and J. Himmelfarb. 2007. Simultaneous determination of total homocysteine, cysteine, cysteinylglycine, and glutathione in human plasma by high-performance liquid chromatography Application to studies of oxidative stress. /. Chromatogr. B Anal. Technol. Biomed. and Life Sci. 852(1-2) 554-561. 

Perhaps the most satisfying hypothesis for the formation of atherosclerotic lesions is that of response to injury in which lesions are precipitated by some form of injury to endothelial cells. The injury may be caused by elevated plasma levels of LDL and modified LDL (oxidized LDL), free radicals (e.g., caused by cigarette smoking), diabetes mellitus, hypertension-induced shear stress, and other factors that lead to focal desquamation of endothelial cells such as elevated plasma homocysteine levels, genetic... 

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