Skip to main content Skip to main navigation menu Skip to site footer

Exploring the role of the combination of propolis and vitamin D3 on VCAM-1 and Caspase-3 expression in preventing atherosclerosis in chronic kidney disease rats

  • Darmawan Ismail ,
  • Bambang Purwanto ,
  • Brian Wasita ,
  • Supomo ,
  • Ketut Putu Yasa ,
  • Soetrisno ,


Abstract

Background: Increased blood pressure that occurs in chronic kidney disease (CKD) is influenced by the occurrence of thickening of blood vessels. This study evaluates the utilization of propolis which acts as an anti-inflammatory and vitamin D3 which plays a role in calcium-phosphate metabolism, that when combined are expected to prevent atherosclerosis.

Methods: This experimental research used a post-test only group design with a total of 24 male rats divided into 3 groups. Subjects were induced to develop CKD with unilateral ureteral obstruction. A combination of 50mg/kgBW of propolis and 0.126mcg/kgBW of vitamin D3 was given orally every morning in the intervention group. Hemodynamics and atherosclerosis status were observed using sonography until week 4. Inflammatory markers with vascular cell adhesion molecule 1 (VCAM-1) and Caspase-3 were evaluated weekly via plasma and target organ samples were immunohistochemically examined at the study’s end.

Results: Propolis and vitamin D3 significantly reduced blood pressure from 156 mmHg at the beginning of the study to 117mmHg at week 4 (p=0.000). Thickening of the aorta occurred in the control and intervention groups but the thickening in the control group (0.90mm) was statistically significantly (p=0.000) higher than the intervention group (0.30mm). There were decreased VCAM-1 and Caspase-3 levels in the intervention group compared to the control group, both in plasma and target organ levels

Conclusion: Utilization of propolis and vitamin D3 combined has a good effect on lowering inflammation, improving hemodynamics and preventing atherosclerosis in chronic kidney disease rat models.

Keywords: Chronic kidney disease Atherosclerosis Propolis Vitamin D3 Inflammation Rat models.

References

  1. Lyngdoh L, Banerjee B, Chowdhury S, Mukherjee R, Naiya SB, Bhattacharya R. Evaluation of atherosclerosis in patients with chronic kidney disease by measuring carotid intima media thickness: An observational study from a tertiary care center in India. Asian J Med Sci. 2021;12(12):50–7. Available from: http://dx.doi.org/10.3126/ajms.v12i12.39547
  2. Iwai T, Kataoka Y, Otsuka F, Asaumi Y, Nicholls SJ, Noguchi T, et al. Chronic kidney disease and coronary atherosclerosis: evidences from intravascular imaging. Expert Rev Cardiovasc Ther. 2019;17(10):707–16. Available from: http://dx.doi.org/10.1080/14779072.2019.1676150
  3. Ku E, Lee BJ, Wei J, Weir MR. Hypertension in CKD: Core Curriculum 2019. Am J Kidney Dis. 2019;74(1):120–31. Available from: http://dx.doi.org/10.1053/j.ajkd.2018.12.044
  4. Stenvinkel P, Chertow GM, Devarajan P, Levin A, Andreoli SP, Bangalore S, et al. Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2. Kidney Int reports. 2021;6(7):1775–87. Available from: https://pubmed.ncbi.nlm.nih.gov/34307974
  5. Mathew RO, Bangalore S, Lavelle MP, Pellikka PA, Sidhu MS, Boden WE, et al. Diagnosis and management of atherosclerotic cardiovascular disease in chronic kidney disease: a review. Kidney Int. 2017;91(4):797–807. Available from: http://dx.doi.org/10.1016/j.kint.2016.09.049
  6. Choi IJ, Lim S, Choo E-H, Kim J-J, Hwang B-H, Kim T-H, et al. Differential Impact of Chronic Kidney Disease on Coronary Calcification and Atherosclerosis in Asymptomatic Individuals with or without Diabetes: Analysis from a Coronary Computed Tomographic Angiography Registry. Cardiorenal Med. 2018/06/29. 2018;8(3):228–36. Available from: https://pubmed.ncbi.nlm.nih.gov/29961069
  7. Kon V, Linton MF, Fazio S. Atherosclerosis in chronic kidney disease: the role of macrophages. Nat Rev Nephrol. 2010/11/23. 2011;7(1):45–54. Available from: https://pubmed.ncbi.nlm.nih.gov/21102540
  8. Martinet W, Coornaert I, Puylaert P, De Meyer GRY. Macrophage Death as a Pharmacological Target in Atherosclerosis. Front Pharmacol. 2019;10:306. Available from: https://pubmed.ncbi.nlm.nih.gov/31019462
  9. Grootaert MOJ, Schrijvers DM, Hermans M, Van Hoof VO, De Meyer GRY, Martinet W. Caspase-3 Deletion Promotes Necrosis in Atherosclerotic Plaques of ApoE Knockout Mice. Oxid Med Cell Longev. 2016/10/26. 2016;2016:3087469. Available from: https://pubmed.ncbi.nlm.nih.gov/27847551
  10. Wang X, Sun Z, Yuan R, Zhang W, Shen Y, Yin A, et al. K-80003 Inhibition of Macrophage Apoptosis and Necrotic Core Development in Atherosclerotic Vulnerable Plaques. Cardiovasc Drugs Ther. 2021; Available from: http://dx.doi.org/10.1007/s10557-021-07237-4
  11. Thayse K, Kindt N, Laurent S, Carlier S. VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques. Biology (Basel). 2020;9(11):368. Available from: https://pubmed.ncbi.nlm.nih.gov/33138124
  12. Fang Y, Sang H, Yuan N, Sun H, Yao S, Wang J, et al. Ethanolic extract of propolis inhibits atherosclerosis in ApoE-knockout mice. Lipids Health Dis. 2013;12:123. Available from: https://pubmed.ncbi.nlm.nih.gov/23941539
  13. Silva H, Francisco R, Saraiva A, Francisco S, Carrascosa C, Raposo A. The Cardiovascular Therapeutic Potential of Propolis-A Comprehensive Review. Biology (Basel). 2021;10(1):27. Available from: https://pubmed.ncbi.nlm.nih.gov/33406745
  14. Trusheva B, Trunkova D, Bankova V. Different extraction methods of biologically active components from propolis: a preliminary study. Chem Cent J. 2007;1:13. Available from: https://pubmed.ncbi.nlm.nih.gov/17880743
  15. Oroian M, Dranca F, Ursachi F. Comparative evaluation of maceration, microwave and ultrasonic-assisted extraction of phenolic compounds from propolis. J Food Sci Technol. 2019/08/16. 2020;57(1):70–8. Available from: https://pubmed.ncbi.nlm.nih.gov/31975709
  16. Song J, Liu J, Luo J, Zhang Q, Xia Y, Shao Q, et al. A modified relief of unilateral ureteral obstruction model. Ren Fail. 2019;41(1):497–506. Available from: https://pubmed.ncbi.nlm.nih.gov/31215300
  17. Martínez-Klimova E, Aparicio-Trejo OE, Tapia E, Pedraza-Chaverri J. Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments. Biomolecules. 2019;9(4):141. Available from: https://pubmed.ncbi.nlm.nih.gov/30965656
  18. Gu L-F, Ge H-T, Zhao L, Wang Y-J, Zhang F, Tang H-T, et al. Huangkui Capsule Ameliorates Renal Fibrosis in a Unilateral Ureteral Obstruction Mouse Model Through TRPC6 Dependent Signaling Pathways. Front Pharmacol. 2020;11:996. Available from: https://pubmed.ncbi.nlm.nih.gov/32719603
  19. Archakova T, Nedosugova L. Risk factors for atherosclerosis and vascular calcification in patients with type 2 diabetes on long-term hemodialysis. Vessel Plus. 2018;2(10):34. Available from: http://dx.doi.org/10.20517/2574-1209.2018.52
  20. Drüeke TB, Floege J. Cardiovascular complications of chronic kidney disease: pioneering studies. Kidney Int. 2020;98(3):522–6. Available from: http://dx.doi.org/10.1016/j.kint.2020.07.001
  21. Silva EH, Wickramatilake CM, Lekamwasam S, Mudduwa LKB, Ubayasiri RA. Vascular dysfunction and atherosclerosis in chronic kidney disease; A distinct entity. J Nephropathol. 2019;8(2):17. Available from: http://dx.doi.org/10.15171/jnp.2019.17
  22. Valdivielso JM, Rodríguez-Puyol D, Pascual J, Barrios C, Bermúdez-López M, Sánchez-Niño MD, et al. Atherosclerosis in Chronic Kidney Disease. Arterioscler Thromb Vasc Biol. 2019;39(10):1938–66. Available from: http://dx.doi.org/10.1161/atvbaha.119.312705
  23. Hiemstra T, Lim K, Thadhani R, Manson JE. Vitamin D and Atherosclerotic Cardiovascular Disease. J Clin Endocrinol Metab. 2019;jc.2019-00194. Available from: https://pubmed.ncbi.nlm.nih.gov/30946457
  24. Carracedo J, Alique M, Vida C, Bodega G, Ceprián N, Morales E, et al. Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence. Front cell Dev Biol. 2020;8:185. Available from: https://pubmed.ncbi.nlm.nih.gov/32266265
  25. Kim J-Y, Shim SH. Medicinal Herbs Effective Against Atherosclerosis: Classification According to Mechanism of Action. Biomol Ther (Seoul). 2019;27(3):254–64. Available from: https://pubmed.ncbi.nlm.nih.gov/30917628
  26. Daleprane JB, Abdalla DS. Emerging roles of propolis: antioxidant, cardioprotective, and antiangiogenic actions. Evid Based Complement Alternat Med. 2013/04/08. 2013;2013:175135. Available from: https://pubmed.ncbi.nlm.nih.gov/23662115
  27. Di Lullo L, House A, Gorini A, Santoboni A, Russo D, Ronco C. Chronic kidney disease and cardiovascular complications. Heart Fail Rev. 2014;20(3):259–72. Available from: http://dx.doi.org/10.1007/s10741-014-9460-9
  28. Choy KW, Murugan D, Leong X-F, Abas R, Alias A, Mustafa MR. Flavonoids as Natural Anti-Inflammatory Agents Targeting Nuclear Factor-Kappa B (NFκB) Signaling in Cardiovascular Diseases: A Mini Review. Front Pharmacol. 2019;10:1295. Available from: https://pubmed.ncbi.nlm.nih.gov/31749703
  29. A IA-JT, A DAK. Effects of Bee Propolis on Blood Pressure Record and Certain Biochemical Parameter in Healthy Volunteers. Ann Coll Med Mosul. 2018;40(1):20–6. Available from: http://dx.doi.org/10.33899/mmed.2018.159191
  30. Silveira MAD, Teles F, Berretta AA, Sanches TR, Rodrigues CE, Seguro AC, et al. Effects of Brazilian green propolis on proteinuria and renal function in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled trial. BMC Nephrol. 2019;20(1):140. Available from: https://pubmed.ncbi.nlm.nih.gov/31023272
  31. Xu X, Yang B, Wang D, Zhu Y, Miao X, Yang W. The Chemical Composition of Brazilian Green Propolis and Its Protective Effects on Mouse Aortic Endothelial Cells against Inflammatory Injury. Molecules. 2020;25(20):4612. Available from: https://pubmed.ncbi.nlm.nih.gov/33050458
  32. Daleprane JB, da Silva Freitas V, Pacheco A, Rudnicki M, Faine LA, Dörr FA, et al. Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis. J Nutr Biochem. 2012;23(6):557–66. Available from: http://dx.doi.org/10.1016/j.jnutbio.2011.02.012
  33. Campos JF, Dos Santos UP, da Rocha PDS, Damião MJ, Balestieri JBP, Cardoso CAL, et al. Antimicrobial, Antioxidant, Anti-Inflammatory, and Cytotoxic Activities of Propolis from the Stingless Bee Tetragonisca fiebrigi (Jataí). Evid Based Complement Alternat Med. 2015/06/22. 2015;2015:296186. Available from: https://pubmed.ncbi.nlm.nih.gov/26185516
  34. Kong D-H, Kim YK, Kim MR, Jang JH, Lee S. Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. Int J Mol Sci. 2018;19(4):1057. Available from: https://pubmed.ncbi.nlm.nih.gov/29614819
  35. Menezes AR, Lamb MC, Lavie CJ, DiNicolantonio JJ. Vitamin D and atherosclerosis. Curr Opin Cardiol. 2014;29(6):571–7. Available from: http://dx.doi.org/10.1097/hco.0000000000000108
  36. Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014;7:69–87. Available from: https://pubmed.ncbi.nlm.nih.gov/24971027

How to Cite

Ismail, D., Purwanto, B., Wasita, B., Supomo, Yasa, K. P., & Soetrisno. (2022). Exploring the role of the combination of propolis and vitamin D3 on VCAM-1 and Caspase-3 expression in preventing atherosclerosis in chronic kidney disease rats. Bali Medical Journal, 11(1), 160–165. https://doi.org/10.15562/bmj.v11i1.3194
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver
Download Citation
Endnote/Zotero/Mendeley (RIS) BibTeX

HTML
1

Total
22

Share