The effects of folic acid on vascular reactivity in a hyperhomocysteinemic rat model

Abstract Objective: This study aimed to investigate the antioxidant effects of folic acid and its effects on contraction and relaxation responses in rat aorta in hyperhomocysteinemic rats. Methods: Thirty-four male Wistar Albino rats were allocated into four groups. Rats in the hyperhomocysteinemia group (Group 1, n=9) received 1g/kg/day methionine via orogastric gavage for 30 days and then injected with intraperitoneal saline for the next 7 days. In the hyperhomocysteinemia+folic acid group (Group 2, n=9), following the administration of methionine for 30 days, folic acid (4mg/kg/day) was delivered intraperitoneally for 7 days. Sham group rats (Group 3, n=8) received orogastric saline for 30 days, which was followed by an IP injection of saline for another 7 days. Animals allocated into the folic acid group (Group 4, n= 7) had orogastric saline for 30 days and intraperitoneal folic acid for 7 days. After 5 weeks of treatment, blood samples were obtained, all animals were sacrificed, and hearts were harvested. Thoracic aortic segments were suspended on individual organ baths, and acetylcholine-induced (endothelium-dependent) relaxation responses of isolated aortic rings were evaluated. Results: Relaxation responses in Group 1 thru 4 were 73.889.96, 76.159.28, 76.618.83, and 69.2615.68, respectively. There was no significant difference in the organ bath in terms of relaxation response to acetylcholine at a dose of 10-9 mM between the groups (F=0.716, p=0.550). Conclusion: Folic acid therapy failed to produce a significant improvement in vascular reactivity. Keywords: Hyperhomocysteinemia, folic acid, vascular reactivity

[1]  M. Feligioni,et al.  Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies , 2019, Front. Nutr..

[2]  Guowei Huang,et al.  Folic acid inhibits homocysteine-induced cell apoptosis in human umbilical vein endothelial cells , 2018, Molecular and Cellular Biochemistry.

[3]  C. Ronco,et al.  Folic Acid and Homocysteine in Chronic Kidney Disease and Cardiovascular Disease Progression: Which Comes First , 2017, Cardiorenal Medicine.

[4]  Joshua D Rabinowitz,et al.  One-Carbon Metabolism in Health and Disease. , 2017, Cell metabolism.

[5]  Qingchun Zeng,et al.  Association between homocysteine levels and calcific aortic valve disease: a systematic review and meta-analysis , 2015, Oncotarget.

[6]  Russell V. Lenth,et al.  Java Applets for Power and Sample Size , 2015 .

[7]  P. Ganguly,et al.  Role of homocysteine in the development of cardiovascular disease , 2015, Nutrition Journal.

[8]  Shuohua Chen,et al.  Homocysteine as a Risk Factor for Hypertension: A 2-Year Follow-Up Study , 2014, PloS one.

[9]  Qiang Zhang,et al.  Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis , 2014, PloS one.

[10]  B. P. Gargari,et al.  Effect of Folic Acid Supplementation on Homocysteine, Serum Total Antioxidant Capacity, and Malondialdehyde in Patients with Type 2 Diabetes Mellitus , 2011, Journal of the American College of Nutrition.

[11]  B. Benoist Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. , 2008 .

[12]  N. Milton Homocysteine inhibits hydrogen peroxide breakdown by catalase , 2008 .

[13]  J. Loscalzo,et al.  Homocysteine and glutathione peroxidase-1. , 2007, Antioxidants & redox signaling.

[14]  R. Draijer,et al.  Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials. , 2007, The American journal of clinical nutrition.

[15]  A. Tasatargil,et al.  Homocysteine-induced changes in vascular reactivity of guinea-pig pulmonary arteries: role of the oxidative stress and poly (ADP-ribose) polymerase activation. , 2007, Pulmonary pharmacology & therapeutics.

[16]  H. Schaff,et al.  Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion. , 2004, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[17]  H. Schaff,et al.  Pharmacological studies on internal mammary artery bypass grafts. Action of endogenous and exogenous vasodilators and vasoconstrictors. , 2002, The Journal of cardiovascular surgery.

[18]  A. Zou,et al.  Implications of Hyperhomocysteinemia in Glomerular Sclerosis in Hypertension , 2002, Hypertension.

[19]  L. Goldman,et al.  Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond. , 2001, JAMA.

[20]  H. Schaff,et al.  Exogenous hyaluronidase induces release of nitric oxide from the coronary endothelium. , 2000, The Journal of thoracic and cardiovascular surgery.

[21]  J. Norman,et al.  Nitric oxide in parturition , 2000, BJOG : an international journal of obstetrics and gynaecology.

[22]  I. Mcdowell,et al.  Homocysteine and endothelial dysfunction: a link with cardiovascular disease. , 2000, The Journal of nutrition.

[23]  Z. Ungvari,et al.  Dysfunction of nitric oxide mediation in isolated rat arterioles with methionine diet-induced hyperhomocysteinemia. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[24]  H. C. Yeo,et al.  Assay of aldehydes from lipid peroxidation: gas chromatography-mass spectrometry compared to thiobarbituric acid. , 1997, Analytical biochemistry.

[25]  G. Stansby,et al.  Homocysteine and vascular disease , 1995, The British journal of surgery.

[26]  N. Cortas,et al.  Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. , 1990, Clinical chemistry.

[27]  Y. Sun,et al.  A simple method for clinical assay of superoxide dismutase. , 1988, Clinical chemistry.

[28]  W. Valentine,et al.  Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. , 1967, The Journal of laboratory and clinical medicine.

[29]  P. Jungers,et al.  Long-term folic acid (but not pyridoxine) supplementation lowers elevated plasma homocysteine level in chronic renal failure. , 1996, Mineral and electrolyte metabolism.

[30]  N. Latruffe,et al.  Peroxisomes , 1994, Springer Laboratory.

[31]  C. Burtis Tietz textbook of Clinical Chemistry , 1994 .

[32]  W. Vermaak,et al.  Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. , 1993, The American journal of clinical nutrition.

[33]  I. Carlberg,et al.  Glutathione reductase. , 1985, Methods in enzymology.

[34]  B. Mannervik,et al.  [59] Glutathione reductase , 1985 .

[35]  H. Aebi,et al.  Catalase in vitro. , 1984, Methods in enzymology.