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Effect of L-Methionine Feeding on Serum Homocysteine and Glutathione Levels in Male and Female Wistar Rats
Advances in Biochemistry
Volume 8, Issue 1, March 2020, Pages: 21-25
Received: Feb. 19, 2020; Accepted: Mar. 10, 2020; Published: Mar. 23, 2020
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Shatha Ahmad Demerchi, School of Science and Technology, University of New England, Armidale, Australia; Technical College/Kirkuk, Northern Technical University, Kirkuk, Iraq
James Robert McFarlane, School of Science and Technology, University of New England, Armidale, Australia
Pierre Dominique Jean Moens, School of Science and Technology, University of New England, Armidale, Australia
Nicola King, School of Biomedical Sciences, University of Plymouth, Plymouth, UK
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Homocysteine (Hcy) is a critical indicator of cardiovascular disease. High levels of Hcy have now been recognised as a risk factor for the development of a wide range of diseases. Hyperhomocysteinemia (Hhcy) can be induced by methionine or Hcy supplementation. On the other hand, Glutathione (GSH) is a major antioxidant in the body and also an important compound for oxidative defence. It is composed of 3 amino acids: cysteine, glutamate, and glycine. Interestingly, methionine is also a crucial compound in GSH synthesis. This study aims to assess the impact of 1% L-methionine feeding (10 or 30 weeks) on the body weight and serum Hcy and GSH levels of young adult (16 weeks) and middle-aged (36 weeks) Wistar rats of both sexes. Serum was analysed for Hcy and reduced GSH levels by liquid chromatography mass spectrometry (LCMS) in response to 1% L-methionine feeding. One percent L-methionine feeding decreased body weight in all conditions investigated, although this only reached significance in males after 10 weeks supplementation and females after 30 weeks supplementation. It also induced a significant increase in the serum Hcy levels of male Wistar rats, whilst having no significant effect on Hcy serum levels in female rats. Finally, we also observed a small increase in serum GSH levels in female Wistar rats but no change in serum GSH levels in the males. These results suggest that methionine feeding affects body weight homeostasis and alters by products of methionine catabolism.
Methionine, Homocysteine, Reduced Glutathione, Body Weight
To cite this article
Shatha Ahmad Demerchi, James Robert McFarlane, Pierre Dominique Jean Moens, Nicola King, Effect of L-Methionine Feeding on Serum Homocysteine and Glutathione Levels in Male and Female Wistar Rats, Advances in Biochemistry. Vol. 8, No. 1, 2020, pp. 21-25. doi: 10.11648/j.ab.20200801.14
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ma Y., Peng D., Liu C., Huang C and Luo J (2017). Serum high concentrations of homocysteine and low levels of folic acid and vitamin B12 are significantly correlated with the categories of coronary artery diseases. BMC Cardiovasc Disorders 17: 37.
Austin R., Lentz S., and Werstuck G (2004). Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differentiation 11: S56-S64.
Selhub J. (1999). Homocysteine metabolism. Ann Rev Nutr 19: 217-246.
Toborek M., and Hennig B (1996). Dietary methionine imbalance, endothelial cell dysfunction and atherosclerosis. Nutr Res 16: 1251-1266.
Troen A. M., Lutgens E., Smith D. E., Rosenberg I. H., and Selhub J (2003). The atherogenic effect of excess methionine intake. PNAS, 100: 15089-15094.
McCully K. S. (1997). Homocysteine Revolution: Keats Publishing.
Allen R. H., Stabler S. P., Savage D. G., and Lindenbaum J (1993). Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J 7: 1344-1353.
Brustolin S., Giugliani R., Félix T. (2010). Genetics of homocysteine metabolism and associated disorders. Braz J Med Biol Res 43: 1-7.
Refsum M. H., Ueland M., Nygård M., and Vollset M. (1998). Homocysteine and cardiovascular disease. Ann Rev Med 49: 31-62.
van Guldener C., and Robinson K. (2000). Homocysteine and renal disease. Semin Thromb Hemost 26: 313-324.
Strain J., Dowey L., Ward M., Pentieva K., and McNulty H. (2004). B-vitamins, homocysteine metabolism and CVD. Proc Nutr Soc, 63: 597-604.
Durand P., Lussier-Cacan S., and Blache D. (1997). Acute methionine load-induced hyperhomocysteinemia enhances platelet aggregation, thromboxane biosynthesis, and macrophage-derived tissue factor activity in rats. FASEB J 11: 1157-1168.
Robin S., Courderot-Masuyer C., Nicod L., Jacqueson A., Richert L., Berthelot A. (2004). Opposite effect of methionine-supplemented diet, a model of hyperhomocysteinemia, on plasma and liver antioxidant status in normotensive and spontaneously hypertensive rats. J Nutrl Biochem 15: 80-89.
Moselhy S., and Demerdash S. (2003). Plasma homocysteine and oxidative stress in cardiovascular disease. Disease markers 19: 27-31.
Boushey C. J., Beresford S. A., Omenn G. S., and Motulsky A. G. (1995). A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 274: 1049-1057.
El-Saleh S. C., Al-Sagair O. A., Al-Khalaf M. I. (2004). Thymoquinone and Nigella sativa oil protection against methionine-induced hyperhomocysteinemia in rats. Intl J Cardiol 93: 19-23.
Ventura P., Panini R., Verlato C., Scarpetta G., and Salvioli G. (2000). Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading. Metab 49: 225-228.
Holford P., and Burne J. (2012). The 10 Secrets Of Healthy Ageing: How to live longer, look younger and feel great: Hachette UK.
Bottiglieri T. (2002). S-Adenosyl-L-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotrophic molecule. Am J Clin Nutr 76: 1151S-1157S.
Aleynik S., and Lieber C. S. (2000). Role of S-adenosylmethionine in hyperhomocysteinemia and in the treatment of alcoholic liver disease. Nutr 16: 1104-1108.
Lu S. C. (2000). S-adenosylmethionine. Intl J Biochem Cell Biol 32: 391-395.
Bostom A. G., Silbershatz H., Rosenberg I. H., Selhub J., D'Agostino R. B., Wolf P. A., Jacques P. F., and Wilson P. W. (1999) Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Int Med 159: 1077-1080.
Diaz V. P., Wolff T., Markovic J., Pallardó F., and Foyer C. (2010). A nuclear glutathione cycle within the cell cycle. Biochem J 431: 169-178.
Maher P. (2005). The effects of stress and aging on glutathione metabolism. Ageing Res Rev 4: 288-314.
Lu S. C. (2009). Regulation of glutathione synthesis. Mol Aspects Med 30: 42-59.
Fukada S. I., Shimada Y., Morita T., and Sugiyama K. (2006). Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in rats. Biosci Biotech Biochem 70: 2403-2409.
Mori N., and Hirayama K. (2000). Long-term consumption of a methionine-supplemented diet increases iron and lipid peroxide levels in rat liver. J Nutr 130: 2349-2355.
Norsidah K-Z., Asmadi A. Y., Azizi A., Faizah O., Kamisah Y. (2013). Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet. J Physiol Biochem 69: 441-449.
Suckow M. A., Weisbroth S. H., and Franklin C. L. (2005). The laboratory rat: Academic Press.
Benevenga N. J. (1974). Toxicities of methionine and other amino acids. J Agricult Food Chem 22: 2-9.
Herrmann M., Taban-Shoma O., Hübner U., Pexa A., Kilter H., Umanskaya N., Straub R. H., Böhm M., and Herrmann W. (2007). Hyperhomocysteinemia and myocardial expression of brain natriuretic peptide in rats. Clin Chem 53: 773-780.
El Aty N. A., Ibrahim H. S., Ramadan R. S. (2012). Does Methionine Supplementation Alters Beta Amyloid Levels in Brain Cells, Liver and kidney Functions? Available at
Hegedüs M., Fekete S., Andrásofszky E., Hullár I. (1998). Effect of methionine and its derivatives on the weight gain and protein utilisation of growing rats. Acta Veterinaria Hungarica 46: 421-429.
Meng B., Gao W., Wei J., Pu L., Tang Z., Guo C. (2015). Quercetin Increases Hepatic Homocysteine Remethylation and Transsulfuration in Rats Fed a Methionine-Enriched Diet. BioMed Res Intl Article ID: 815210.
de Rezende M. M., and D’Almeida V. (2014). Central and systemic responses to methionine-induced hyperhomocysteinemia in mice. PloS one, 9: e105704.
Zhou J., Møller J., Danielsen C. C., Bentzon J., Ravn H. B., Austin R. C., and Falk E. (2001). Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 21: 1470-1476.
Nygård O., Vollset S. E., Refsum H., Stensvold I., Tverdal A., Nordrehaug J. E., Ueland P. M., and Kvåle G. (1995). Total plasma homocysteine and cardiovascular risk profile: the Hordaland Homocysteine Study. JAMA 274: 1526-1533.
Fukagawa N. K., Martin J. M., Wurthmann A., Prue A. H., Ebenstein D., and O’Rourke B. (2000). Sex-related differences in methionine metabolism and plasma homocysteine concentrations. Am J Clin Nutr 72: 22–29.
Bianchi G., Brizi M., Rossi B., Ronchi M., Grossi G., and Marchesini G. (2000). Synthesis of glutathione in response to methionine load in control subjects and in patients with cirrhosis. Metabolism 49: 1434-1439.
Mosharov E., Cranford M. R., and Banerjee R. (2000). The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes. Biochem 39: 13005-13011.
Vyas S., Sharma H., and Vyas R. (2015). Oxidative stress and Antioxidant level in the serum of osteoarthritis patients. Intl J Scientific Res Pub 5: 1-4.
Pastore A., Alisi A., di Giovamberardino G., Crudele A., Ceccarelli S., Panera N., Dionisi-Vici C., and Nobili V. (2014). Plasma Levels of Homocysteine and Cysteine Increased in Pediatric NAFLD and Strongly Correlated with Severity of Liver Damage. Intl J Mol Sci 15: 21202-21214.
Ballatori N., Krance S. M., Notenboom S., Shi S., Tieu K., and Hammond C. L. (2009). Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 390: 191-214.
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