Administration of valine, leucine, and isoleucine improved plasma cholesterol and mitigated the preatherosclerotic lesions in rats fed with hypercholesterolemic diet

Open access

Abstract

Hypercholesterolemia has a major contribution to the occurrence and progression of atherosclerotic lesions. Recent studies report the involvement of branched-chain amino acids in cholesterol methabolism. The aim of this research was to evaluate the role of valine, leucine and isoleucine on the occurrence and progression of atherosclerosis in rats receiving hypercholesterolic diet. Material and methods: 50 male Wistar rats distributed into five groups with the following type of diets: group I (control) received standard diet; group II - cholesterol; group III - cholesterol and valine; group IV - cholesterol and leucine; group V - cholesterol and isoleucine. The experimental study was conducted over a period of 2 months. The animals were evaluated for the serum levels of total cholesterol at the beginning of the experiment, after 1 month and after 2 months. The collected tissue fragments of heart and aorta were prepared for the examination by optical microscopy in order to identify the atherosclerotic changes. Results: The most increased values of serum cholesterol were recorded in rats from group II (p=0.001), for the second and third evaluation. The histological examination showed early histopathological lesions on the vascular intima for the groups treated with cholesterol, valine, leucine, and isoleucine. These early changes (the occurrence of some superficial endothelial erosions, adhesion of erythrocytes and platelets) were correlated with the degree of the arterial wall damage, of the leukocytes adhesion to the arterial intima, and the discontinuities of the internal elastic lamina. Conclusion: The comparative study of the effects of the three essential amino acids revealed that valine induced a faster response than leucine and isoleucine on the improvement of biochemical parameters, but there were no significant differences between the three amino acids in terms of their protective ability, demonstrated by the histopathological lesion assessment.

1. Mc Nair E, Qureshi M, Prasad K, Pearce C. Atherosclerosis and hypercholesterolemic Age-Rage axis. Int J Angiol. 2016 Jun;25(2):110-6. DOI: 10.1055/s-0035-1570754

2. Li Q, Gu W, Ma X, Liu Y, Jiang L, Feng R, et al. Amino acid and biogenic amine profile deviations in an oral glucose tolerance test: a comparison between healthy and hyperlipidaemia individuals based on targeted metabolomics. Nutrients. 2016 Jun;8(6):379. DOI: 10.3390/nu8060379

3. Vergeer M, Holleboom AG, Kastelein JJP, Kuivenhoven JA. The HDL hypothesis: does highdensity lipoprotein protect from atherosclerosis? J Lipid Res. 2010 Aug;51(8):2058-73. DOI: 10.1194/jlr.R001610

4. Zhao Y, Dai XY, Zhou Z, Zhao GX, Wang X, Xu MJ. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice. Acta Pharmacol Sin. 2016 Feb;37(2):196-203. DOI: 10.1038/aps.2015.88

5. Badimon L, Vilahur G. LDL-cholesterol versus HDL-cholesterol in the atherosclerotic plaque: inflammatory resolution versus thrombotic chaos. Ann N Y Acad Sci. 2012 Apr;1254:18-32. DOI: 10.1111/j.1749-6632.2012.06480.x

6. Zhang S, Zeng X, Ren M, Mao X, Qiao S. Novel metabolic and physiological function of branched chain amino acids: a review. J Anim Sci Biotechnol. 2017 Jan;8:10. DOI: 10.1186/s40104-016-0139-z

7. Cojocaru E, Zamfir C, Zamosteanu N, Trandafirescu M, Cotuţiu C. The effects of branched chain aminoacids on LDL-cholesterol in experimental animals subjected to dietary hypercholesterolemia. Rev Med Chir Soc Med Nat Iasi. 2012 Jan-Mar;116(1):200-6.

8. Yang R, Dong J, Zhao H, Li H, Guo H, et al. Association of Branched-Chain Amino Acids with Carotid Intima-Media Thickness and Coronary Artery Disease Risk Factors. PLoS ONE. 2014 Jun;9(6):e99598. DOI: 10.1371/journal.pone.0099598

9. Cojocaru E, Zamfir C, Amihăesei C, Trandafirescu M, Leon M, Mitu F. The influence of branched amino acids on LDL-cholesterol levels in a model of experimental atherosclerosis. Romanian Journal of Functional and Clinical, Macro- and Microscopical Anatomy and of Anthropology 2012;11(1):35-40.

10. *** National Research Council of the National Academies. Guide for the Care and Use of laboratory animals. 8th edition. The National Academies Press, Washington, USA, 2011.

11. *** Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDF

12. *** The ARRIVE Guidelines - Animal Research: Reporting In Vivo Experiments. Available at http://www.nc3rs.org.uk/page.asp?id=1357.

13. Festing MFW, Overend P, Gaines Das R, Cortina Borja M, Berdoy M. The design of animal experiments: reducing the number of animals in research through better experimental design, Laboratory Animal Handbooks Series 14. Royal Society of Medicine Press, London, 2002.

14. Richmond W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of the total cholesterol serum. Clin Chem. 1973 Dec;19(12):1350-6.

15. Bennett BJ, Davis RC, Civelek M, Orozco L, Wu J, Qi H et al. Genetic architecture of atherosclerosis in mice: A Systems Genetics Analysis of Common Inbred Strains. PLoS Genet. 2015 Dec;11(12):e1005711. DOI: 10.1371/journal.pgen.1005711

16. Anandhi R, Thomas PA, Geraldine P. Evaluation of the anti-atherogenic potential of chrysin in Wistar rats. Mol Cell Biochem. 2014 Jan;385(1-2):103-13. DOI: 10.1007/s11010-013-1819-z

17. Xiao F, Du Y, Ly Z, Chen S, Zhu J, Sheng H, et al. Effects of essential amino acids on lipid metabolism in mice and humans. J Mol Endocrinol. 2016 Nov;57(4):223-231. DOI: 10.1530/JME-16-0116

18. Kitsy A, Carney S, Vivar JC, Knight MS, Pointer MA. Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes. PLoS One. 2014 Jul;9(7):102615. DOI: 10.1371/journal.pone.0102615

19. Miasoedov NF, Shubina TA, Obergan T, Grigorieva ME, Andreeva LA, Liapina LA. Cholesterol-lowering effect of the regulatory peptide Pro-Gly-Pro-Leu. Vopr Pitan. 2013;82(5):41-5.

20. Matoba T, Sato K, Egashira K. Mouse models of plaque rupture. Curr Opin Lipidol. 2013 Oct;24(5):419-25. DOI: 10.1097/MOL.0b013e3283646e4d

21. Garjani A, Azarmiy Y, Zakheri A, Allaf Akbari N, Andalib S, Maleki-Dizaji N. Vascular Dysfunction in Short-Term Hypercholesterolemia despite the Absence of Atherosclerotic Lesions. J Cardiovasc Thorac Res. 2011 Aug;3(3):73-7.

22. De Brito FCF. Inhibition of inflammatory pathways promotes an improving effect on endothelial dysfunction: The effects of Longxuetongluo capsule in an experimental model of atherosclerosis. Atherosclerosis. 2016 Oct;255:111-2. DOI: 10.1016/j.atherosclerosis. 2016.10.040

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information


IMPACT FACTOR 2017: 0.400
5-year IMPACT FACTOR: 0.320



CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2017: 0.144
Source Normalized Impact per Paper (SNIP) 2017: 0.195

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 135 135 8
PDF Downloads 52 52 1