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

Year 2021, , 151 - 157, 24.04.2021

Melek Yılmaz , Hüseyin Gemalmaz , Cihan Yücel , Serkan Ketenciler , Uğur Gürcün Berent Dişçigil

https://doi.org/10.38053/acmj.880037

Abstract

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

Keywords

Hyperhomocysteinemia, folic acid, vascular reactivity

References

• Onat A, Can G. Prevalence of heart disease in our adults, new coronary events and prevalence of death from heart. TEKHARF; 2017.
• Pahwa R, Jialal I. Atherosclerosis. StatPearls. Treasure Island (FL). StatPearls Publishing; 2018.
• Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease. Cell Metab 2017; 25: 27–42.
• de Benoist B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 2008; 29: S238–44.
• Tinelli C, Di Pino A, Ficulle E, Marcelli S, Feligioni M. Hyperhomocysteinemia as a risk factor and potential nutraceutical target for certain pathologies. Front Nutr 2019; 6: 49.
• Cui S, Li W, Wang P, Lv X, Gao Y, Huang G. Folic acid inhibits homocysteine-induced cell apoptosis in human umbilical vein endothelial cells. Mol Cell Biochem 2018; 444: 77–86.
• McDowell IF, Lang D. Homocysteine and endothelial dysfunction: a link with cardiovascular disease. J Nutr 2000; 130: 369-372.
• Ledingham M, Thomson AJ, Greer IA, Norman JE. Nitric oxide in parturition. BJOG An Int J Obstet Gynaecol 2000; 107: 581–93.
• Ungvari Z, Pacher P, Rischák K, Szollár L, Koller A. Dysfunction of nitric oxide mediation in isolated rat arterioles with methionine diet-induced hyperhomocysteinemia. Arterioscler Thromb Vasc Biol 1999; 19: 1899–904.
• Chauveau P, Chadefaux B, Coudé M, Aupetit J, Kamoun P, Jungers P. Long-term folic acid (but not pyridoxine) supplementation lowers elevated plasma homocysteine level in chronic renal failure. Miner Electrolyte Metab 1996; 22: 106-9.
• Li N, Chen Y-F, Zou A-P. Implications of hyperhomocysteinemia in glomerular sclerosis in hypertension. Hypertens (Dallas, Tex 1979) 2002; 39: 443–8.
• Burtis CA, Ashwood ER. Tietz textbook of clinical chemistry. Philadelphia 1999; 1999: 1654–5.
• Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990; 36: 1440–3.
• Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497–500.
• Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158–69.
• Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol 1985; 113: 484–90.
• Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121–6.
• Discigil B, Evora PRB, Pearson PJ, Viaro F, Rodrigues AJ, Schaff H V. Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion. Brazilian J Med Biol Res 2004; 37: 259–65.
• Evora PRB, Pearson PJ, Discigil B, Oeltjen MR, Schaff H V. Pharmacological studies on internal mammary artery bypass grafts: Action of endogenous and exogenous vasodilators and vasoconstrictors. J Cardiovasc Surg (Torino) 2002; 43: 761.
• Evora PRB, Pearson PJ, Chua YL, Discigil B, Schaff H V. Exogenous hyaluronidase induces release of nitric oxide from the coronary endothelium. J Thorac Cardiovasc Surg 2000; 120: 707–11.
• Lenth R. Java Applets for Power and Sample Size [Computer software] [Internet] 2009 [cited 2018 May 24]. Available from: https: //homepage.divms.uiowa.edu/~rlenth/Power/
• Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J 2015; 14: 6.
• Cao H, Hu X, Zhang Q, et al. Homocysteine level and risk of abdominal aortic aneurysm: a meta-analysis. PLoS One 2014; 9: e85831.
• Wu G, Xian J, Yang X, al. Association between homocysteine levels and calcific aortic valve disease: a systematic review and meta-analysis. Oncotarget 2018; 9: 8665–74.
• Berwanger CS, Jeremy JY, Stansby G. Homocysteine and vascular disease. Br J Surg 1995; 82: 726–31.
• Tasatargil A, Sadan G, Karasu E. Homocysteine-induced changes in vascular reactivity of guinea-pig pulmonary arteries: role of the oxidative stress and poly (ADP-ribose) polymerase activation. Pulm Pharmacol Ther 2007; 20: 265–72.
• Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993; 57: 47–53.
• Lubos E, Loscalzo J, Handy DE. Homocysteine and glutathione peroxidase-1. Antioxid Redox Signal 2007; 9: 1923–40.
• GM C. Peroxisomes. In: The Cell: A Molecular Approach 2nd edition 2000.
• Milton NGN. Homocysteine inhibits hydrogen peroxide breakdown by catalase. Open Enzym Inhib J 2008; 1.
• Eken A. Rat kan ve doku örneklerinde oksidatif stres parametreleri. J Clin Anal Med 2017: 1-5.
• Aghamohammadi V, Gargari BP, Aliasgharzadeh A. Effect of folic acid supplementation on homocysteine, serum total antioxidant capacity, and malondialdehyde in patients with type 2 diabetes mellitus. J Am Coll Nutr 2011; 30: 210–5.
• Liu J, Yeo HC, Doniger SJ, Ames BN. Assay of aldehydes from lipid peroxidation: gas chromatography-mass spectrometry compared to thiobarbituric acid. Anal Biochem 1997; 245: 161–6.
• Wang Y, Chen S, Yao T, et al. Homocysteine as a risk factor for hypertension: a 2-year follow-up study. PLoS One 2014; 9.
• de Bree A, van Mierlo LA, Draijer R. Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2007; 86: 610–7.
• Cianciolo G, De Pascalis A, Di Lullo L, Ronco C, Zannini C, La Manna G. folic acid and homocysteine in chronic kidney disease and cardiovascular disease progression: which comes first? Cardiorenal Med 2017; 7: 255–66.
• Tice JA, Ross E, Coxson PG, 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. JAMA 2001; 286: 936–43.