Study on the influence of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives on the lipid metabolism in experiment
DOI:
https://doi.org/10.14739/2310-1210.2021.3.207465Keywords:
xanthines, hyperlipidemia, lipoproteinsAbstract
Statin side effects are not a rare occurrence, in particular dyspeptic disorders, insomnia, headache, skin erythema, rash are often noted. All of this determines scientists to find new effective and low-toxic hypolipidemic agents. Various natural and synthetic xanthine derivatives have been recognized as therapeutically potential compounds and reported to control various diseases. Therefore, the study of new xanthine derivatives and their hypolipidemic effects, which would have a significant therapeutic effect with minimal side effects, is relevant.
The aim of the study was to examine the effect of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives on lipidogram parameters in experimental laboratory rats.
Materials and methods. The objects of the study were 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives. The experiments were performed in white laboratory Wistar rats weighing 180–220 g. Experimental modeling of hyperlipidemia – tween model: intraperitoneal administration of tween-80 at a dose of 200 mg/100 g body weight. The test compounds were administered orally, simultaneously with tween, at a dose of 1/10 of LD50 (previously calculated by Prozorovsky express method) for 6 days. The following indicators of lipidogram were determined: total cholesterol (TC), high-density lipoprotein cholesterol (HDL cholesterol), low-density lipoprotein cholesterol (LDL cholesterol), triglycerides (TG) and atherogenic index of plasma: TC – HDL cholesterol / HDL cholesterol. The experiments were carried out with respect to Bioethical rules and norms.
Results. The studies have shown data on the hypolipidemic activity of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkane acid derivatives. According to the conditional efficiency index Ʃ, which included the overall percentage of the following indicators – total cholesterol, low-density lipoprotein cholesterol and triglycerides, the leading compounds were 2439 (87.47 %), 6047 (82.30 %). The reference drug atorvastatin had a value of 82.98 %.
Conclusions. The major compound was 2439 identified among all compared to the control group. The prospect of further research is a more detailed study on the ability of xanthine derivatives to exhibit hypolipidemic effects and to influence oxidative stress in various hyperlipidemic models.
References
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., Graham, I. M., Halliday, A., Landmesser, U., Mihaylova, B., Pedersen, T. R., Riccardi, G., Richter, D. J., Sabatine, M. S., Taskinen, M. R., Tokgozoglu, L., … ESC Scientific Document Group. (2020). 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal, 41(1), 111-188. https://doi.org/10.1093/eurheartj/ehz455
Steffens, D., Bramlage, P., Scheeff, C., Kasner, M., Hassanein, A., Friebel, J., & Rauch-Kröhnert, U. (2020). PCSK9 inhibitors and cardiovascular outcomes. Expert Opinion on Biological Therapy, 20(1), 35-47. https://doi.org/10.1080/14712598.2020.1677604
Baum, S. J., Toth, P. P., Underberg, J. A., Jellinger, P., Ross, J., & Wilemon, K. (2017). PCSK9 inhibitor access barriers-issues and recommendations: Improving the access process for patients, clinicians and payers. Clinical Cardiology, 40(4), 243-254. https://doi.org/10.1002/clc.22713
Zodda, D., Giammona, R., & Schifilliti, S. (2018). Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs. Pharmacy, 6(1), Article 10. https://doi.org/10.3390/pharmacy6010010
Brozin, D., & Raal, F. J. (2018). Novel approaches to lipid-lowering therapy. South African Medical Journal, 108(4), 262-265. https://doi.org/10.7196/SAMJ.2018.v108i4.13234
Mach, F., Ray, K. K., Wiklund, O., Corsini, A., Catapano, A. L., Bruckert, E., De Backer, G., Hegele, R. A., Hovingh, G. K., Jacobson, T. A., Krauss, R. M., Laufs, U., Leiter, L. A., März, W., Nordestgaard, B. G., Raal, F. J., Roden, M., Santos, R. D., Stein, E. A., Stroes, E. S., … European Atherosclerosis Society Consensus Panel. (2018). Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. European Heart Journal, 39(27), 2526-2539. https://doi.org/10.1093/eurheartj/ehy182
Toth, P. P., Patti, A. M., Giglio, R. V., Nikolic, D., Castellino, G., Rizzo, M., & Banach, M. (2018). Management of Statin Intolerance in 2018: Still More Questions Than Answers. American Journal of Cardiovascular Drugs, 18(3), 157-173. https://doi.org/10.1007/s40256-017-0259-7
Basu, S., Barawkar, D. A., Ramdas, V., Waman, Y., Patel, M., Panmand, A., Kumar, S., Thorat, S., Bonagiri, R., Jadhav, D., Mukhopadhyay, P., Prasad, V., Reddy, B. S., Goswami, A., Chaturvedi, S., Menon, S., Quraishi, A., Ghosh, I., Dusange, S., Paliwal, S., … Mookhtiar, K. A. (2017). A2B adenosine receptor antagonists: Design, synthesis and biological evaluation of novel xanthine derivatives. European Journal of Medicinal Chemistry, 127, 986-996. https://doi.org/10.1016/j.ejmech.2016.11.007
Mikhalchenko, E. K., Аleksandrova, K. V., Levich, S. V., & Sinchenko, D. M. (2017). Synthesis and physical-chemical properties of 3-benzyl8-propylxanthinyl-7-acetic acid and its derivatives. Current issues in pharmacy and medicine: science and practice, 10(1), 14-19. https://doi.org/10.14739/2409-2932.2017.1.93430
Mironov, A. N. (Ed.). (2012). Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Chast' pervaya [Guidance on non-clinical studies of pharmaceuticals. Part one]. Grif i K. [in Russian].
Ostapenko, A. А. (2012). Hipolipidemichna aktyvnist novykh pokhidnykh 7-β-hidroksy-γ-(mono- ta dykhlorfenoksy)propilksantyniv pry eksperymentalnii hiperlipidemii. (Avtoref. dis. … kand. farm. nauk). [Hypolipidemic activity of some derivatives of 7-β-hydroxy-γ-(mono- and dichlorophenoxy)propylxanthines in the experimental hyperlipidemy]. (Extended abstract of candidate’s thesis). Kharkiv. [in Ukrainian].
European Parliament, & European Council. (2010, October 20). Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes Text with EEA relevance. Official Journal of the European Union, L 276, 33-79. http://data.europa.eu/eli/dir/2010/63/oj
Ivanchenko, D. G., Romanenko, N. I., & Kornienko, V. I. (2018). Synthesis and Antioxidant Activity of 8-bromo-7-(2-hydroxy-3-aryloxyprop-1-yl)theophyllines. Chemistry of Natural Compounds, 54(3), 532-534. https://doi.org/10.1007/s10600-018-2397-9
Singh, N., Shreshtha, A. K., Thakur, M. S., & Patra, S. (2018). Xanthine scaffold: scope and potential in drug development. Heliyon, 4(10), Article e00829. https://doi.org/10.1016/j.heliyon.2018.e00829
Cook, N. R., Mora, S., & Ridker, P. M. (2018). Lipoprotein(a) and Cardiovascular Risk Prediction Among Women. Journal of the American College of Cardiology, 72(3), 287-296. https://doi.org/10.1016/j.jacc.2018.04.060
Zhu, X., Yang, L., Xu, F., Lin, L., & Zheng, G. (2017). Combination therapy with catechins and caffeine inhibits fat accumulation in 3T3-L1 cells. Experimental and Therapeutic Medicine, 13(2), 688-694. https://doi.org/10.3892/etm.2016.3975
Wu, B. N., Kuo, K. K., Chen, Y. H., Chang, C. T., Huang, H. T., Chai, C. Y., Dai, Z. K., & Chen, I. J. (2016). Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice. International Journal of Molecular Sciences, 17(8), Article 1345. https://doi.org/10.3390/ijms17081345
El-Kalyoubi, S. A., Fayed, E. A., & Abdel-Razek, A. S. (2017). One pot synthesis, antimicrobial and antioxidant activities of fused uracils: pyrimidodiazepines, lumazines, triazolouracil and xanthines. Chemistry Central Journal, 11(1), Article 66. https://doi.org/10.1186/s13065-017-0294-0
Liu, L., Nagai, I., Gao, Y., Matsushima, Y., Kawai, Y., & Sayama, K. (2017). Effects of catechins and caffeine on the development of atherosclerosis in mice. Bioscience, Biotechnology, and Biochemistry, 81(10), 1948-1955. https://doi.org/10.1080/09168451.2017.1364618
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