Research Article
BibTex RIS Cite

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

Year 2021, , 151 - 157, 24.04.2021
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

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.
Year 2021, , 151 - 157, 24.04.2021
https://doi.org/10.38053/acmj.880037

Abstract

Thanks

Teşekkürler.

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.
There are 37 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Articles
Authors

Melek Yılmaz 0000-0001-6018-4962

Hüseyin Gemalmaz 0000-0003-3995-3557

Cihan Yücel 0000-0002-1941-0873

Serkan Ketenciler 0000-0003-1528-6788

Uğur Gürcün This is me

Berent Dişçigil This is me 0000-0003-4746-3400

Publication Date April 24, 2021
Published in Issue Year 2021

Cite

AMA Yılmaz M, Gemalmaz H, Yücel C, Ketenciler S, Gürcün U, Dişçigil B. The effects of folic acid on vascular reactivity in a hyperhomocysteinemic rat model. Anatolian Curr Med J / ACMJ / acmj. April 2021;3(2):151-157. doi:10.38053/acmj.880037

TR DİZİN ULAKBİM and International Indexes (1b)

Interuniversity Board (UAK) Equivalency:  Article published in Ulakbim TR Index journal [10 POINTS], and Article published in other (excuding 1a, b, c) international indexed journal (1d) [5 POINTS]

Note: Our journal is not WOS indexed and therefore is not classified as Q.

You can download Council of Higher Education (CoHG) [Yüksek Öğretim Kurumu (YÖK)] Criteria) decisions about predatory/questionable journals and the author's clarification text and journal charge policy from your browser. https://dergipark.org.tr/tr/journal/3449/file/4924/show

Journal Indexes and Platforms: 

TR Dizin ULAKBİM, Google Scholar, Crossref, Worldcat (OCLC), DRJI, EuroPub, OpenAIRE, Turkiye Citation Index, Turk Medline, ROAD, ICI World of Journal's, Index Copernicus, ASOS Index, General Impact Factor, Scilit.


The indexes of the journal's are;

18596


asos-index.png

f9ab67f.png

WorldCat_Logo_H_Color.png

      logo-large-explore.png

images?q=tbn:ANd9GcQgDnBwx0yUPRKuetgIurtELxYERFv20CPAUcPe4jYrrJiwXzac8rGXlzd57gl8iikb1Tk&usqp=CAU

index_copernicus.jpg


84039476_619085835534619_7808805634291269632_n.jpg





The platforms of the journal's are;

COPE.jpg

images?q=tbn:ANd9GcTbq2FM8NTdXECzlOUCeKQ1dvrISFL-LhxhC7zy1ZQeJk-GGKSx2XkWQvrsHxcfhtfHWxM&usqp=CAUicmje_1_orig.png

cc.logo.large.png

ncbi.png

ORCID_logo.pngimages?q=tbn:ANd9GcQlwX77nfpy3Bu9mpMBZa0miWT2sRt2zjAPJKg2V69ODTrjZM1nT1BbhWzTVPsTNKJMZzQ&usqp=CAU


images?q=tbn:ANd9GcTaWSousoprPWGwE-qxwxGH2y0ByZ_zdLMN-Oq93MsZpBVFOTfxi9uXV7tdr39qvyE-U0I&usqp=CAU






The
 
indexes/platforms of the journal are;

TR Dizin Ulakbim, Crossref (DOI), Google Scholar, EuroPub, Directory of Research Journal İndexing (DRJI), Worldcat (OCLC), OpenAIRE, ASOS Index, ROAD, Turkiye Citation Index, ICI World of Journal's, Index Copernicus, Turk Medline, General Impact Factor, Scilit 


EBSCO, DOAJ, OAJI is under evaluation.

Journal articles are evaluated as "Double-Blind Peer Review"