Investigation of the Pathogenesis and Treatment Efficiency of Bevacizumab-Induced Hypertension in the Rat Model
Keywords:Bevacizumab, hypertension, valsartan, rat model
AbstractBevacizumab is known to reduce Vascular Endothelial Growth Factor (VEGF) to undetectable levels when used in conjunction with chemotherapy. Hypertension is a frequent adverse effect of bevacizumab, although its mechanism(s) remain unclear. In this study, our aim was to examine the pathogenesis of bevacizumab-induced hypertension and to investigate the treatment efficacy of valsartan. A total of 24 Wistar Albino female rats were included in the study. Rats were divided into three groups with 8 rats in each, as follows: The control group, bevacizumab group and bevacizumab + valsartan group. Blood pressure, blood urea nitrogen and serum creatinine levels were measured, urine samples were collected for 24 hours statistical analyses were performed using IBM SPSS 20 software pack. Nephrectomy specimens in bevacizumab and bevacizumab + valsartan groups exhibited varying degrees of renal injury. Although valsartan was able to reduce the bevacizumab-induced rise in blood pressure, it could not prevent the development of nephropathy. Conclusions these findings suggest that hypertension occurring secondary to bevacizumab treatment in rats may be associated with mechanisms involving renal injury.
George, B. A., Zhou, X. J., & Toto, R. (2007). Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis, 49(2), e23-29. doi:10.1053/j.ajkd.2006.11.024
Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., . . . Kabbinavar, F. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med, 350(23), 2335-2342. doi:10.1056/NEJMoa032691
Izzedine, H., Rixe, O., Billemont, B., Baumelou, A., & Deray, G. (2007). Angiogenesis inhibitor therapies: focus on kidney toxicity and hypertension. Am J Kidney Dis, 50(2), 203-218. doi:10.1053/j.ajkd.2007.04.025
Johnson, D. H., Fehrenbacher, L., Novotny, W. F., Herbst, R. S., Nemunaitis, J. J., Jablons, D. M., . . . Kabbinavar, F. (2004). Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol, 22(11), 2184-2191. doi:10.1200/JCO.2004.11.022
Miller, K. D., Chap, L. I., Holmes, F. A., Cobleigh, M. A., Marcom, P. K., Fehrenbacher, L., . . . Rugo, H. S. (2005). Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol, 23(4), 792-799. doi:10.1200/JCO.2005.05.098
Sugimoto, H., Hamano, Y., Charytan, D., Cosgrove, D., Kieran, M., Sudhakar, A., & Kalluri, R. (2003). Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem, 278(15), 12605-12608. doi:10.1074/jbc.C300012200
Syrigos, K. N., Karapanagiotou, E., Boura, P., Manegold, C., & Harrington, K. (2011). Bevacizumab-induced hypertension: pathogenesis and management. BioDrugs, 25(3), 159-169. doi:10.2165/11590180-000000000-00000
Touyz, R. M., Lang, N. N., Herrmann, J., van den Meiracker, A. H., & Danser, A. H. J. (2017). Recent Advances in Hypertension and Cardiovascular Toxicities With Vascular Endothelial Growth Factor Inhibition. Hypertension, 70(2), 220-226. doi:10.1161/HYPERTENSIONAHA.117.08856
Zhao, T., Wang, X., Xu, T., Xu, X., & Liu, Z. (2017). Bevacizumab significantly increases the risks of hypertension and proteinuria in cancer patients: A systematic review and comprehensive meta-analysis. Oncotarget, 8(31), 51492-51506. doi:10.18632/oncotarget.18190
How to Cite
Publishing your paper with Medical Laboratory Technology Journal (MLTJ) means that the author or authors retain the copyright in the paper. MLTJ granted an author(s) rights to put the paper onto a website, distribute it to colleagues, give it to students, use it in your thesis etc, even commercially. The author(s) can reuse the figures and tables and other information contained in their paper published by MLTJ in future papers or work without having to ask anyone for permission, provided that the figures, tables or other information that is included in the new paper or work properly references the published paper as the source of the figures, tables or other information, and the new paper or work is not direct at private monetary gain or commercial advantage.
MLTJ journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge. This journal is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. This license lets others remix, transform, and build upon the material for any purpose, even commercially. MLTJ journal Open Access articles are distributed under this Creative Commons Attribution-ShareAlike 4.0 International License (CC BY-SA). Articles can be read and shared for All purposes under the following conditions:
BY: You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.SA: If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original.