METHIONINE SUPPLEMENTATION INDUCES THYMUS VEGF-A EXPRESSION AND HEMATOLOGICAL CHANGES IN RATS

Authors

  • Aggoun Cherifa Constantine1 university
  • Lamda Souad
  • Naimi Dalila

Abstract

Objective: The present study evaluates the effects of methionine supplementation on the thymus histology and the peripheral blood in albino Wistar rats.

Methods: The animals were divided into two groups. The experimental group (Met)(500mg/Kg /day, orally) and the control (C). Blood was collected for C reactive protein (CRP), total protein, Malondialdehyde (MDA) and blood smear tests, then thymuses were harvested for Histology and immune histochemistry.

Results: Methionine intake caused an increase in CRP (P<0, 01), total protein (P<0,001) and MDA levels (P<0, 01) in addition to several hematological changes expressed by crenation of red blood cell membranes and irregular leucocyte nuclei. Histological investigation of experimental thymus gave dramatic involution of lobules and presented of apoptotic zones especially in the medulla. Immuno histochemical expression of VEGF- A were positive in septa and blood vessels at the corticomedullary junction.

Conclusion: Methionine supplementation produces hematological changes, a thymic involution, and seemed to promote the angiogenesis process in the thymus of adult rats.

Keywords: Methionine, Thymus, Blood cells, VEGF-A, Histopathology, Involution, Angiogenesis.

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Author Biography

Aggoun Cherifa, Constantine1 university

Département de biologie animale, faculté de science de la nature et de la vie

References

Hardwick DF, Applegarth DA, Cockcroft DM, Ross PM, Calder RJ. Pathogenesis of methionine-induced toxicity. Metab-Clin Exp 1970;19(5):381-91.

Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia; an effect reversible with vitamin C therapy. Cir 1999;99:1156-60.

Domagala TB, Libura M, Szczeklik A. Hyperhomocysteinemia following oral methionine load is associated with increased lipid peroxidation. Thromb Res 1997;87(4):411-6.

Toborek M, Hemrig B. Dietary methionine imbalance, endothelial cell dysfunction and atherosclerosis. Nut Res 1996;16(7):1251-66.

Fujimoto S, Togane Y, Matsuzaki C, Yamashina S, Nakano H, Yamasaki J, et al. Effects of long-term administrationof methionine on vascular endotheliumin rabbits. Nutr Metab Cardiovasc Dis 2003;13:20-7.

Caro P, Gomez J, Lopez-Torres M, Sanchez I, Naudı A, Jove M, et al. Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver. Biogerontol 2008;9:183-96.

Yalcinkaya S, Unlucerci Y, Giris M, Olgac V, Dogru-Abbasoglu S, Uysal M. Oxidative and nitrosative stress and apoptosis in the liver of rats fed on hight methionine diet: Protective effect of taurine. Nutr 2009;25:436-44.

Dunlevy LPE, Burren KA, Chitty LS, Copp AJ, Greene NDE. Excess methionine suppresses the methylation cycle and inhibits neural tube closure in mouse embryos. FEBS Lett 2006;580:2803-7.

Gomez J, Caro P, Sanchez, Naudi A, Jove M, Portero-Otin M, et al. Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and oxidative DNA damage in rat liver and heart. J Bioenerg Biomembr 2009;41:309-21.

Miller A, Mujumdar V, Shek E, Guillot J, Angelo M, Palmer L, et al. Hyperhomocysteinemia induces multiorgan damage. Heart Vessels 2000;15:135-43.

Webb RE, Leslie Jr DM, Lochmiller RL, Masters RE. Immune function and hematology of male cotton rats (Sigmodonhispidus) in response to food supplementation and methionine. Comp Biochem Physiol Part A 2003;136:577-89.

AL-Mayah AAS. Immune response of broiler chicks to DL-methionine supplementation at different ages. Int J Poult Sci 2006;5(2):169-72.

Wu BY, Cui HM, Peng X, Fang J, Cui W, Liu XD. Effect of methionine deficiency on thymus and the subsets and proliferation of peripheral blood T-cell, and serum IL-2 contents in broilers. J Integr Agric 2012;11(6):1009-19.

Anderson M, Anderson SK, Farr AG. Thymic vasculature: organizer of the medullary epithelial compartments? Int Immunol 2000;12(7):1105-10.

Garlick PJ. Toxicity of methionine in humans. J Nutr 2006;136:1722-5.

Spindel E, Mccully KS. Conversion of methionine to homocysteine thiolactone in liver. Biochim Biophys Acta 1974;343:687-91.

Boldyrev AA. Molecular mechanisms of homocysteine toxicity. Biochem (Moscow) 2009;74(6):589-98.

Cook JW, Taylor LM, Orloff SL, Landry GJ, Landry GJ, Moneta GL, et al. Homocysteine and arterial diseaseexperimental mechanisms. Vascular Pharmacol 2002;38:293-300.

Hussein MA, Mahmoud AE, Salama AR, Abdel Moneim FG. Lowering homocysteine decreases levels and expression of VEGF165 and endostatin. J Surg Res 2008;146:202-10.

Oosterbaan AM, Steegers E AP, Ursem NTC. The effects of homocysteine and folic acid on angiogenesis and VEGF expression during chicken vascular development. Micro Res 2012;83:98-104.

Mullur SM, Terszowski G, Blum C, Haller C, Anquez V, Kuschert S, et al. Gene targeting of VEFG-A in thymus epithelium disrupts thymus blood vessel architecture. PNAS 2005;102(30):10587-92.

Joory KD, Levik JR, Mortimer PS, Bates DO. Vascular endothelial growth factor C (VEGF-C) in normal human tissues. Lymph Res Biol 2006;4:73-82.

Ansari MN, Nigam GK, Bhandari U. Effect of folic acid on hematological changes in methionine-induced hyperhomocysteinemia in rats. Indian J Pharm Sci 2009;71(3):270-5.

Rasouli M, Kiasari AM, Bagheri B. Total and differential leukocytes counts, but not hsCRP, ESR, and five fractioned serum proteins have significant potency to predict stable coronary artery disease. Clin Chim Acta 2007;377:127-32.

Bradford MM. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye-binding. Anal Biochem 1976;72:248-54.

Lqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S. Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing perzymes in doly malemia: possible role in protection against chemical carcinogenesis and toxicity. Pharmacol Toxicol 2003;92(1):33-8.

Lefèvre G, Beljean-Leymarie M, Beyerle F, Bonnefont-Rousselot D, Cristol JP, Therond P, et al. Evaluation dela peroxydation lipidique par le dosage des substances réagissant avec l'acide thiobarbiturique. Annales Biol Clin 1998;56(3):305-19.

Gilani GS, Peace RW, Botting HG. Effects of folate, vitamin B-12 and vitamin B-6 supplementation on methionine-induced hyperhomocysteinemia in rats. Nut Res 2001;21:1501-7.

Robin S, Courderot-Masuyer C, Nicod L, Jacqueson A, Richert L, Berthelot A. Opposite effect of methionine supplemented diet, a model of hyperhomocysteinemia, on plasma and liver antioxidant status in normotensive and spontaneously hypertensive rats. J Nutr Biochem 2004;15:80-9.

Youngsun S, Mikyung C, Chungwon C, Rosenfeld ME. Methionine-induced hyperhomocysteinemia modulates lipoprotein profile and oxidative stress but not progression of atherosclerosis in aged apolipoprotein E knockout mice. J Med Food 2009;12(1):137-44.

Meenakshi S, Santosh KR, Manisha T, Ramesh C. Effect of hyperhomocysteinemia on cardiovascular risk factors and initiation of atherosclerosis in Wistar rats. Eur J Pharm 2007;574(1):49-60.

Ahmed MA, Elosaily GM. Role of oxytocin in deceleration of early atherosclerotic inflammatory processes in adult male rats. Int J Clin Exp Med 2011;4(3):169-78.

Da Cunha AA, Ferreira AGK, Wyse ATS. Increased inflammatory markers in brain and blood of rats subjected to acute homocysteine administration. Metab Brain Dis 2010;25:199-206.

Yalçınkaya S, ÜnlÜcerci Y, Uysal M. Methionine-supplemented diet augments hepatotoxicity and prooxidant status in chronically ethanol-treated rats. Exp Toxicol Pathol 2007;58:455-9.

Park CM, Cho CW, Rosenfeld ME, Song YS. Methionine supplementation accelerates oxidative stress and nuclear factor κB activation in livers of C57BL/6 mice. J Med Food 2008;11(4):667-74.

Gomez J, Sanchez-Roman I, Gomez A, Sanchez C, Suarez H, Lopez-Torres M, et al. Methionine and homocysteine modulate the rate of ROS generation of isolated mitochondria in vitro. J Bioenerg Biomembr 2011;43(4):377-86.

Benevenga NJ, Steele RD. Adverse effects of excessive consumption of amino acids. Ann Rev Nutr 1984;4:157-81.

Nigam GK, Ansari MN, Bhandari U. Effect of rosuvastatin on methionine-induced hyperhomocysteinemia and haematological Changes in Rats. Basic Clin Pharmacol Toxicol 2008;103:287-92.

Mashkina AP, Cizkova D, Vanicky I, Boldyrev AA. NMDA Receptors are expressed in lymphocytes activated both in vitro and in vivo. Cell Mol Neurobiol 2010;30:901-7.

Boldyrev AA, Bryushkova EA, Vladychenskaya EA. NMDA receptors in immune competent cells. Biochem (Moscow) 2012;77(2):128-34.

Makhro A, Wang J, Vogel J, Boldyrev AA, Gassmann M, Kaestner L, et al. Functional NMDA receptors in rat erythrocytes. Am J Physiol Cell Biol 2010;298:1315-25.

Vladychenskaya EA, Tyulina OV, Boldyrev AA. Effect of homocysteine and homocysteic acid on glutamate receptors on rat lymphocytes. Bull Exp Biol Med 2006;142(7):55-8.

Bryushkova EA, Vladychenskaya EA, Stepanova MS, Boldyrev AA. Effect of homocysteine on properties of neutrophils activated in vivo. Biochem (Moscow) 2011;76(4):467-72.

Zainullina LF, Yamidanov RS, Vakhitov VA, Vakhitova YV. NMDA receptors as a possible component of store-operated Ca2+ entry in human T-lymphocytes. Biochem (Moscow) 2011;76(11):1220-6.

Quaglino D, Ronchetti IP. Cell death in the rat thymus: a minireview. Apop 2001;6:389-401.

Picerno I, Chirico C, Condello S, Visalli G, Ferlazzo Nadia, Gorgone G, et al. Homocysteine induces DNA damage and alterations in proliferative capacity of T-lymphocytes: a model for immunosenescence? Biogerontol 2007;8:111-9.

Zhang X-Y, Jianati, Aihua. Changes of plasma nitric oxide and plasma endothelin-1 levels in hyperhomocysteinemia rats: verification of endothelial dysfunction. J Clin Rehab T Eng Res 2007;11(41):8242-6.

Andrew RC, Shundi G, Judy Z, Julie J, Ann C, Gavin T, et al. VEGF-mediated cross-talk within the neonatal murine thymus. Blood 2009;113:2723-31.

Andrew RC, Batul T S, Shundi G, Lisa AK, Julie J, Jacob A, et al. Rapid thymic reconstitution following bone marrow transplantation in neonatal mice is VEGF-dependent. Biol Blood Marrow Transplant 2012;18:683-9.

Chinn IK, Blackburn CC, Manley NR, Sempowsk GD. Changes in primary lymphoid organs with aging. Semin Immunol 2012;24:309-20.

Cimpeana AM, Raicaa M, Encicab S, Corneac R, Bocana V. Immunohistochemical expression of vascular endothelial growth factor A (VEGF), and its receptors (VEGFR1, 2) in normal and pathologic conditions of the human thymus. Ann Anat 2008;190:238-45.

Hyun-Joo P, Mi NK, Jong-Gab K, Yun-Hee B, Moon-Kyoung B, Hee-Jun W, et al. 2731Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat. Biochem Biophys Acta 2007;1773:1462-72.

Guerzoni AR, Biselli PM, Godoy MF, Souza DR, Haddad R, Eberlin MN. et al. Homocysteine and MTHFR and VEGF gene polymorphisms: impact on coronary artery disease. Arq Bras Cardiol 2009;92(4):263-8.

Published

01-02-2015

How to Cite

Cherifa, A., L. Souad, and N. Dalila. “METHIONINE SUPPLEMENTATION INDUCES THYMUS VEGF-A EXPRESSION AND HEMATOLOGICAL CHANGES IN RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 2, Feb. 2015, pp. 234-8, https://journals.innovareacademics.in/index.php/ijpps/article/view/3875.

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