Effect of bortezomib on fatty liver in a rat model of atherosclerosis
Keywords:atherosclerosis, bortezomib, fatty liver, interleukin-6, proteasome
Introduction and Aim: Fatty liver is associated with atherosclerosis even though the exact mechanism remains unknown. Fatty liver and atherosclerosis correlate with inflammation. Interleukin 6 (IL-6) is recognized as an inflammatory marker. Bortezomib is a proteasome inhibitor that will inhibit the proteasome pathway and is expected to inhibit inflammation in atherosclerosis. The current research aimed to investigate the effect of bortezomib on the fatty liver of atherosclerosis rats and to analyze its correlation with serum IL-6 concentration.
Materials and Methods: Experimental subjects were 18 male Wistar rats (Rattus novergicus) divided into three treatment groups, namely atherosclerosis group (I), atherosclerosis + bortezomib group (II), and control group (III). Bortezomib (50 ?g/kg BW) was given twice intraperitoneally, on day 1 and day 3. The presence of fatty liver was evaluated using the percentage system. Serum IL-6 concentrations were measured using enzyme-linked immunosorbent assay kits.
Results: The highest amount of fatty liver was found in the atherosclerosis group (group I) (38.33%), while the lowest was in the control group (group III) (5.83%). There was a decreasing fatty liver percentage due to bortezomib administration (group II) (29.17%), and it was statistically significant. There is a significant correlation between the degree of fatty liver and serum IL-6 concentration.
Conclusion: The administration of bortezomib 50 ?g/kg BW in atherosclerosis model rats can reduce the occurrence of fatty liver by reducing the inflammatory process.
Pallavi, M., Suchitra, M., Rao, S.P.V.L. Role of adipokines in the pathogenesis of nonalcoholic fatty liver disease. J Clin Sci Res. 2015;4(1):31. DOI: https://doi.org/10.15380/2277-5706.JCSR.14.072
Xu, X., Lu, L., Dong, Q., Li, X., Zhang, N., Xin, Y., et al., Research advances in the relationship between nonalcoholic fatty liver disease and atherosclerosis. Lipids Health Dis [Internet]. 2015;14(1):1-8. DOI: https://doi.org/10.1186/s12944-015-0141-z
Geovanini, G.R., Libby, P. Atherosclerosis and inflammation?: overview and updates. 2018;(June):1243-1252. DOI: https://doi.org/10.1042/CS20180306
Hedin, U., Matic, L.P. Recent advances in therapeutic targeting of inflammation in atherosclerosis. Journal of Vascular Surgery. 2019. DOI: https://doi.org/10.1016/j.jvs.2018.10.051
Ismawati, Oenzil, F., Yanwirasti, Yerizel, E. Changes in expression of proteasome in rats at different stages of atherosclerosis. Anat Cell Biol [Internet]. 2016;49(2):99. DOI: https://doi.org/10.5115/acb.2016.49.2.99
Eldridge, A.G., O’Brien, T. Therapeutic strategies within the ubiquitin proteasome system. Cell Death Differ. 2010;17(1):4-13. DOI: https://doi.org/10.1038/cdd.2009.82
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):1418-1426. DOI: https://doi.org/10.1161/ATVBAHA.112.249342
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. 2017;18(4). DOI: https://doi.org/10.3390/ijms18040781
Wilck, N., Ludwig, A. Targeting the ubiquitin-proteasome system in atherosclerosis: Status Quo, challenges, and perspectives. Antioxidants and Redox Signaling. 2014;21(17):2344-2363. DOI: https://doi.org/10.1089/ars.2013.5805
Oliva, J., French, S.W., Li, J., Gorce, F.B. Proteasome inhibitor treatment reduced fatty acid, triacylglycerol and cholesterol synthesis. Exp Mol Pathol. 2012;93(1):26-34. DOI: https://doi.org/10.1016/j.yexmp.2012.03.006
Ludwig, A., Fechner, M., Wilck, N., Meiners, S., Grimbo, N., Baumann, G., et al. Potent anti-inflammatory effects of low-dose proteasome inhibition in the vascular system. J Mol Med. 2009;87(8):793-802. DOI: https://doi.org/10.1007/s00109-009-0469-9
Ambarwati, L. 2020. Effect of extracts of Eleutherine bulbosa and Cinnamomum burmanii on cholesterol, triglyceride levels and features of HFD-induced fatty liver. Thesis, The State Islamic University of Maulana Malik Ibrahim Malang, Malang.
Sasso, M., Barna, I.T., Ziol, M., Miette, V., Fournier, C., Sandrin, L., et al. Novel controlled attenuation parameter for noninvasive assessment of steatosis using Fibroscan®: Validation in chronic hepatitis C. J Viral Hepat. 2012;19(4):244-253. DOI: https://doi.org/10.1111/j.1365-2893.2011.01534.x
Kampschulte, M., Stöckl, C., Langheinrich, A.C., Althöhn, U., Bohle, R.M., Krombach, G.A., et al. Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis. Lab Investig. 2014;94(11):1273-1282. DOI: https://doi.org/10.1038/labinvest.2014.112
Rinella, M.E. Nonalcoholic fatty liver disease a systematic review. JAMA - J Am Med Assoc. 2015;313(22):2263-2273. DOI: https://doi.org/10.1001/jama.2015.5370
Tousoulis, D., Oikonomou, E., Economou, E.K., Crea, F., Kaski, J.C. Inflammatory cytokines in atherosclerosis: Current therapeutic approaches. Eur Heart J. 2016;37(22):1723-1735. DOI: https://doi.org/10.1093/eurheartj/ehv759
Reiss, A.B., Siegart, N.M., Leon, J.D. Interleukin-6 in atherosclerosis: atherogenic or atheroprotective? Clin Lipidol [Internet]. 2017;12(1):14-23.
Mohamed, A. Role of Serum Adiponectin, IL-6 and Hs CRP in Nonalcoholic Fatty Liver Egyptian Patients. Int J Biochem Res Rev. 2014;4(6):493-504. DOI: https://doi.org/10.9734/IJBCRR/2014/10240
How to Cite
Copyright (c) 2022 Biomedicine
This work is licensed under a Creative Commons Attribution 4.0 International License.