Effect of proteasome inhibitor on serum 8-OHdG and aortic SOD2  in a rat model of atherosclerosis

ismawati ismawati; Ilhami Romus; Mukhyarjon; Jihan Salsabilqis; Nadia Wulandari

doi:10.15562/bmj.v11i1.3126

Effect of proteasome inhibitor on serum 8-OHdG and aortic SOD2 in a rat model of atherosclerosis

ismawati ismawati ,

Ilhami Romus ,

Mukhyarjon ,

Jihan Salsabilqis ,

Nadia Wulandari ,

pdf |
DOI: https://doi.org/10.15562/bmj.v11i1.3126 |
Published: 2022-04-30

Abstract

Background: Numerous studies have been performed to analyze the effect of proteasome inhibitors on atherosclerosis. However, there is still controversy and the mechanism of action of proteasome inhibitors is still not clearly understood. This study aimed to analyze the effect of proteasome inhibitor on 8-hydroxy-2′-deoxyguanosine (8-OHdG) level in the serum of atherosclerotic rats and the antioxidant expression of Superoxide Dismutase 2 (SOD2) in the aorta.

Methods: The sample was 18 rats with the strain Wistar rats aged 2-3 months. The sample was grouped into normal (N) group got a standard feed, A1 induced by atherosclerosis, and A2 induced by atherosclerosis and given proteasome inhibitor. The proteasome inhibitor was a bortezomib dose of 50 µg/kg BW/day given on days one and three. After four days of treatment, rats were sacrificed, and the aorta removal was done for analyzing the tunica intima-media thickness (IMT) and SOD2 expression assessment using immunohistochemistry, and serum 8-OHdG measurement was done using the ELISA method. SOD2 expression assessment was carried out quantitatively using Adobe Photoshop.

Results: We established a decrease in IMT in the A2 group compared to the A1 group and an enhancement of SOD2 expression and a decrease in 8-OHdG levels in the A2 group compared to the A1 group, although not statistically significant.

Conclusion: In our findings showed bortezomib can prevent thickening tunica intima-media in the aorta, although does not reduce serum 8-OHdG levels and did not significantly increase SOD2 expression in the aorta.

References

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Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid Intima-Media Thickness for Atherosclerosis. :18–31.
Wilck N, Ludwig A. Targeting the ubiquitin-proteasome system in atherosclerosis: Status Quo, challenges, and perspectives. Antioxidants and Redox Signaling. 2014.
Shukla SK, Rafiq K. Proteasome biology and therapeutics in cardiac diseases. Transl Res. 2019;205:64–76.
Ismawati, Oenzil F, Yanwirasti, Yerizel E. Changes in expression of the proteasome in rats at different stages of atherosclerosis. Anat Cell Biol. 2016;49(2):99.
Wilck N, Fechner M, Dan C, Stangl V, Stangl K, Ludwig A. The Effect of Low-Dose Proteasome Inhibition on Pre-Existing Atherosclerosis in LDL Receptor-Deficient Mice. Int J Mol Sci [Internet]. 2017 Apr 7;18(4):781. Available from: https://pubmed.ncbi.nlm.nih.gov/28387708
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Wilck N, Fechner M, Dreger H, Hewing B, Arias A, Meiners S, et al. Attenuation of early atherogenesis in low-density lipoprotein receptor-deficient mice by proteasome inhibition. Arterioscler Thromb Vasc Biol. 2012;32(6):1418–26.
Gimbrone MA, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4):620–36.
Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021;20(9):689–709.
Sharifi-Rad M, Anil Kumar N V., Zucca P, Varoni EM, Dini L, Panzarini E, et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front Physiol. 2020;11(July):1–21.
Halliwell, Barry; Gutteridge JMC. Free Radicals in Biology and Medicine. 5th ed. Oxford University Press; 2015.
Kroese LJ, Scheffer PG. 8-Hydroxy-2′-Deoxyguanosine and Cardiovascular Disease: a Systematic Review. Curr Atheroscler Rep. 2014;16(11):1–8.
Di Minno A, Turnu L, Porro B, Squellerio I, Cavalca V, Tremoli E, et al. 8-Hydroxy-2-deoxyguanosine levels and cardiovascular disease: a systematic review and meta-analysis of the literature. Antioxid Redox Signal. 2016;24(10):548–55.
Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res. 2017;120(4):713–35.
Dreger H, Westphal K, Wilck N, Baumann G, Stangl V, Stangl K, et al. Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2. Cardiovasc Res. 2010 Jan;85(2):395–403.
Al-Joufi F, Al-Ani IM, Saxena AK, Talib NA, Mokhtar RH, Ku-Zaifah N. Assessment of the anti-atherosclerotic effect of Eurycoma longifolia extract on high-fat diet model in rats. I: Histological study. Eur J Anat. 2016;20:131–6.
Lehr HA, Mankoff DA, Corwin D, Santeusanio G, Gown AM. Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer. J Histochem Cytochem. 1997;
Xiang F, Shuanglun X, Jingfeng W, Ruqiong N, Yuan Z, Yongqing L, et al. Association of serum 8-hydroxy-2′-deoxyguanosine levels with the presence and severity of coronary artery disease. Coron Artery Dis. 2011;22(4):223–7.
Mahat RK, Singh N, Rathore V, Arora M, Yadav T. Cross-sectional correlates of oxidative stress and inflammation with glucose intolerance in prediabetes. Diabetes Metab Syndr Clin Res Rev. 2019;13(1):616–21.
Tabas I, Wang Y. Emerging roles of mitochondria ROS in atherosclerotic lesions: causation or association? J Atheroscler Thromb. 2014;23929.
Dennis JM, Stocker R. Actions of antioxidants in the protection against atherosclerosis. Free Radical Biology and Medicine. 2012;53:863–84.
Kim JM, Kim HG, Son CG. Tissue-specific profiling of oxidative stress-associated transcriptome in a healthy mouse model. Int J Mol Sci. 2018;19(10).

[1] Barquera S, Pedroza-Tobías A, Medina C, Hernández-Barrera L, Bibbins-Domingo K, Lozano R, et al. Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease. Arch Med Res. 2015;46(5):328–38.

[2] Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019;234(10):16812–23.

[3] Mensah GA, Wei GS, Sorlie PD, Fine LJ, Rosenberg Y, Kaufmann PG, et al. Decline in Cardiovascular Mortality: Possible Causes and Implications. Circ Res [Internet]. 2017 Jan 20;120(2):366–80. Available from: https://pubmed.ncbi.nlm.nih.gov/28104770

[4] Robbin basic pathology. 9th ed. 2013.

[5] Andreou I, Sun X, Stone PH, Edelman ER, Feinberg MW. miRNAs in atherosclerotic plaque initiation, progression, and rupture. Trends in Molecular Medicine. 2015.

[6] Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid Intima-Media Thickness for Atherosclerosis. :18–31.

[7] Wilck N, Ludwig A. Targeting the ubiquitin-proteasome system in atherosclerosis: Status Quo, challenges, and perspectives. Antioxidants and Redox Signaling. 2014.

[8] Shukla SK, Rafiq K. Proteasome biology and therapeutics in cardiac diseases. Transl Res. 2019;205:64–76.

[9] Ismawati, Oenzil F, Yanwirasti, Yerizel E. Changes in expression of the proteasome in rats at different stages of atherosclerosis. Anat Cell Biol. 2016;49(2):99.

[10] Wilck N, Fechner M, Dan C, Stangl V, Stangl K, Ludwig A. The Effect of Low-Dose Proteasome Inhibition on Pre-Existing Atherosclerosis in LDL Receptor-Deficient Mice. Int J Mol Sci [Internet]. 2017 Apr 7;18(4):781. Available from: https://pubmed.ncbi.nlm.nih.gov/28387708

[11] Nunes AT, Annunziata CM. Proteasome inhibitors: structure and function. Semin Oncol. 2017;44(6):377–80.

[12] Wilck N, Fechner M, Dreger H, Hewing B, Arias A, Meiners S, et al. Attenuation of early atherogenesis in low-density lipoprotein receptor-deficient mice by proteasome inhibition. Arterioscler Thromb Vasc Biol. 2012;32(6):1418–26.

[13] Gimbrone MA, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4):620–36.

[14] Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021;20(9):689–709.

[15] Sharifi-Rad M, Anil Kumar N V., Zucca P, Varoni EM, Dini L, Panzarini E, et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front Physiol. 2020;11(July):1–21.

[16] Halliwell, Barry; Gutteridge JMC. Free Radicals in Biology and Medicine. 5th ed. Oxford University Press; 2015.

[17] Kroese LJ, Scheffer PG. 8-Hydroxy-2′-Deoxyguanosine and Cardiovascular Disease: a Systematic Review. Curr Atheroscler Rep. 2014;16(11):1–8.

[18] Di Minno A, Turnu L, Porro B, Squellerio I, Cavalca V, Tremoli E, et al. 8-Hydroxy-2-deoxyguanosine levels and cardiovascular disease: a systematic review and meta-analysis of the literature. Antioxid Redox Signal. 2016;24(10):548–55.

[19] Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res. 2017;120(4):713–35.

[20] Dreger H, Westphal K, Wilck N, Baumann G, Stangl V, Stangl K, et al. Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2. Cardiovasc Res. 2010 Jan;85(2):395–403.

[21] Al-Joufi F, Al-Ani IM, Saxena AK, Talib NA, Mokhtar RH, Ku-Zaifah N. Assessment of the anti-atherosclerotic effect of Eurycoma longifolia extract on high-fat diet model in rats. I: Histological study. Eur J Anat. 2016;20:131–6.

[22] Lehr HA, Mankoff DA, Corwin D, Santeusanio G, Gown AM. Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer. J Histochem Cytochem. 1997;

[23] Xiang F, Shuanglun X, Jingfeng W, Ruqiong N, Yuan Z, Yongqing L, et al. Association of serum 8-hydroxy-2′-deoxyguanosine levels with the presence and severity of coronary artery disease. Coron Artery Dis. 2011;22(4):223–7.

[24] Mahat RK, Singh N, Rathore V, Arora M, Yadav T. Cross-sectional correlates of oxidative stress and inflammation with glucose intolerance in prediabetes. Diabetes Metab Syndr Clin Res Rev. 2019;13(1):616–21.

[25] Tabas I, Wang Y. Emerging roles of mitochondria ROS in atherosclerotic lesions: causation or association? J Atheroscler Thromb. 2014;23929.

[26] Dennis JM, Stocker R. Actions of antioxidants in the protection against atherosclerosis. Free Radical Biology and Medicine. 2012;53:863–84.

[27] Kim JM, Kim HG, Son CG. Tissue-specific profiling of oxidative stress-associated transcriptome in a healthy mouse model. Int J Mol Sci. 2018;19(10).

Effect of proteasome inhibitor on serum 8-OHdG and aortic SOD2 in a rat model of atherosclerosis

Abstract

References

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