The reduction of aorta histopathological images through inhibition of reactive oxygen species formation in hypercholesterolemia rattus norvegicus treated with polysaccharide peptide of Ganoderma lucidum

Document Type : Original Article

Authors

1 Department of Biomedical, Faculty of Medicine, Brawijaya University, Malang, Indonesia

2 Department of Cardiology, Faculty of Medicine, Brawijaya University, Malang, Indonesia

3 Department of Cardiology, Faculty of Medicine, Syiah Kuala University, Aceh, Indonesia

4 Bachelor Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia

Abstract

Objective(s):Atherosclerosis is chronic inflammatory process triggered by oxidative stress. Oxidative stress can increase hydrogen peroxide (H2O2)level, which induce atherosclerosis through the processes such as formation of perivascular adipose tissue (PVAT), foam cells, and atherosclerotic plaque. Antioxidant is needed to control negative effects of oxidative stress. One source of antioxidant, which has potential to be developed, is PsP from Ganoderma lucidum. This study aims to prove the effect of PsP in decreasing H2O2, PVAT, foam cells and atherosclerotic plaque.
Materials and Methods: This study was experimental randomized post-test with control group design using 25 Rattus norvegicus Wistar strain rats. Rats were divided into 5 groups (negative control, positive control, and 3 high-fat diet group with PsP dose: 50, 150, 300 mg/kgBW). Measured parameters were H2O2, PVAT, foam cell, and atherosclerotic plaques. Analysis of variance (ANOVA) was used for statistical analysis, followed by post hoc test.
Results: Mean H2O2 levels, PVAT thickness, foam cell numbers, and atherosclerotic plaque were low in negative control group. ANOVA showed that PsP significantly (P<0.05) reduced H2O2 levels, PVAT thickness, foam cells numbers and atherosclerotic plaque width.
Conclusion: PsP dose of 300 mg/kgBW has the most significant effect in decreasing H2O2 levels, PVAT thickness, number of foam cells, and atherosclerotic plaque width. Based on the results of this research, PsP can be recommended as antioxidant to control pathogenesis of atherosclerosis.

Keywords


1. Frostegard J. SLE, Atherosclerosis and Cardiovascular Disease. J Intern Med 2005; 257:485-495.
2. World Health Organization. Integrated management of cardiovascular risk. geneva: World Health Organization; 2011.
3. Abbass S, Yazdi T, Rezaei A, Azari JB, Hejazi A, Shakeri MT, et al. Prevalence of atherosclerotic plaques in autopsy cases with noncardiac death. Iran J Pathol 2009; 4:101- 104.
4. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473:317-325.
5. Frostegard J. Immunity, atherosclerosis, and cardiovascular disease. BMC Med 2013; 11:117.
6. American Heart Association. Atherosclerosis. Available at: http://www.heart.org/HEARTORG/ Conditions/Cholesterol/WhyCholesterolMatters/Atherosclerosis_UCM_305564_Article.jsp. Accessed on November 18th 2013.
7. Joanne LR, Christopher T, Richard CMS, Giovanni EM, Mark AH, Geraldine FC. Endothelial dysfunction and reduced antioxidant protection in an animal model of the developmental origins of cardiovascular disease. J Physiol 2008; 4709-4720.
8. Bahorun T, Soobrattee MA, Luximon-Ramma V, Aruoma OI. Free Radicals and Antioxidants in Cardiovaskular Health and Disease. Internet J Med Update 2006; 1:1-17.
9. Göran K. Inflammation and immune response in atherosclerosis. Curr Atheroscler Rep 2009; 1:150-155.
10. Kustiyah I, Prasetyo A, Sarjadi. Pengaruh Berbagai Variasi Dosis Ekstrak Morinda citrifolia terhadap Kadar Lipid Serum dan Perkembangan Lesi Atherosklerotik pada Aorta Abdominalis Tikus Wistar. Media Medika Indonesiana 2003; 38:193-202.
11. Suryohudoyo P. Kapita Selekta Ilmu Kedokteran Molekuler. CV Sagung Seto. Jakarta: 2000.
12. Mansjoer A, Triyanti K, Savitri R, Wardhani WI, Setiowulan W. editors. Kapita Selekta Kedokteran Jilid 1. Jakarta: Media Aesculapius; 2005; 588.
13. Lee HY, Després JP, Koh KK. Perivascular adipose tissue in the pathogenesis of cardiovascular disease. Atherosclerosis 2013; 230:177-184.
14. Verhagen SN, Visseren F. Perivascular adipose tissue as a cause of atherosclerosis. Atherosclerosis 2011; 214:3-10.
15. Liu GS, Chan EC, Higuchi M, Dusting GJ, Jiang F. Redox mechanism in regulation of adipocyte differentiation : beyond a general stress esponse. Cells 2012; 1:976-993.
16. Meijer RI, Serne EH, Smulders YM, van Hinsbergh V, Yudkin JS, Eringa EC. Perivascular adipose tissue and its role in type 2 diabetes and cardiovascular disease. Curr Diab Rep 2011; 11:211–217.
17. Eringa EC, Bakker W, Van Hinsbergh V. Paracrine regulation of vascular tone, inflammation and insulin sensitivity by perivascular adipose tissue. Vasc Pharmacol 2012; 56:204–209.
18. Douglas G, Channon KM. The pathogenesis of atherosclerosis. Medicine 2010; 38:8.
19. Shworak, NW. Canonical Nuclear Factor-Kappa B Signaling in Atherosclerosis. 2010. Available at: http://www.abcam.com. Accessed on November 23th 2013.
20. Crowther MA. Pathogenesis of atherosclerosis. ASH Education Book 2005; 1:436-441.
21. Kabo, Peter. Atherosklerosis. Mengungkap Pengobatan Penyakit Jantung Koroner. Jakarta: Gramedia Pustaka Utama 2008.
22. Wei-Ting Hung, Shwu-Huey Wang, Chung-Hsuan Chen, Wen-Bin Yang. Structure Determination of β-Glucans from Ganoderma lucidum with Matrix-assisted Laser Desorption/ionization (MALDI) Mass Spectrometr. Molecules 2008; 13:1538-1550.
23. You YH, Lin ZB. Protective effects of G. lucidum polysaccharides peptide on injury of macrophages induced by reactive oxygen species. Acta Pharmacol Sin 2002; 23:787-791.
24. Jia J, Zhang X, Hua YS, Wua Y, Wang QZ, Li N, et al. Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats. Food Chem 2008; 115:32–36.
25. Hyam P. Understanding and Maintaining the Cryostat; A Practical Guide to Frozen Section Technique. Springer Science+Business Media; LLC 2010.
26. Peter SR, Delia CS. Fixation, Staining and Coverslipping of Frozen Section Slides; A Practical Guide to Frozen Section Technique. Springer Science+Business Media; LLC 2010.
27. Julia AR, Primaningtyas K, Putri VD. Pengaruh Pemberian Bubuk Jamur Tiram Putih (Pleourotus ostreatus) Per Sonde terhadap Jumlah Foam Cell pada Dinding Aorta Tikus Putih Galur Wistar (Rattus Norvegicus) yang Diberi Diet Aterogenik. Malang: Fakultas Kedokteran Universitas Brawijaya; 2012.
28. Mitchell R. Pocket Companion to Robbins and Cotran Pathologic Basis of Disease. 7th ed. 2006.
29. Widiastuti N. Penggunaan Fraksi Etil Asetat Ekstrak Metanolik Buah Merah (Pandanusconoideus Lam.) sebagai Antioksidan dengan Parameter Aktivitas Glutation S-Transferase Sitosol Hepar Tikus. Yogyakarta: Fakultas Farmasi Universitas Gajah Mada; 2010.
30. Sesso HD, Gaziano JM, Liu S, Julie EB. Flavonoid intake and the risk of cardiovascular disease in women. Am J Clin Nutr 2003; 77:1400-1408.
31. Suyoso, H. Uji Antioksidan dan Identifikasi Senyawa Aktif dari Ekstrak Tanaman Anting-Anting (Acalyphaindica L.). Malang: Universitas Islam Negeri Maulana Malik Ibrahim; 2011.
32. Ramprasath VR, Shanthi P, Sachdanandam P. Immunomodulatory and anti-inflammatory effects of Semecarpus Anacardium LINN. nut milk extract in experimental inflammatory conditions. Biol Pharm Bull 2006; 29:693–700.
33. Rodríguez-Martínez MA, García-Cohen EC, Baena AB, González R, Salaíces M, Marín J. Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats; endothelial modulation and mechanism involved. Br J Pharmacol 2009; 125:1329–1335.
34. Collins T, Cybulsky MI. NF-KB : Pitoval mediator or innocent bystander in atherogenesis. J Clin Investn 2001; 107:255-263.
35. Char MD. The pathophysiology of acute coronary syndrome. J Emergency Med Cardiac Research 2005; 1:1-6.