DOI: https://doi.org/10.24959/cphj.19.1512

The study of the efficacy of combined medicines of quercetin and glucosamine derivatives in rats with the end-stage renal failure

S. K. Shebeko

Abstract


Chronic kidney disease (CKD) is the most significant pathology among diseases of the urinary system, which leads to the inevitable development of renal failure. Currently, there are no effective treatments for the end-stage form of CKD in clinical practice.
Aim. To study of the effect of combined medicines of quercetin with glucosamine derivatives in the experiment using various routes of administration on the course of the end-stage renal failure.
Materials and methods. The study was performed on the model of adenine-induced nephropathy in rats. Test samples were administered intragastrically (80 mg/kg) and intramuscularly (30 mg/kg) for 4 weeks starting in 4 weeks after beginning of the experiment. Corvitin was used as a reference drug in the dose of 34 mg/kg. The efficacy of test drugs was assessed by indicators of the kidney functional state and nitrogen metabolism.
Results. In 8 weeks after the pathology simulation under the influence of both test objects a positive effect on the course of renal failure was observed. In this case, an injection combination of quercetin with N-acetylglucosamine significantly (p<0.05) exceeded the efficacy of the oral combination. Under its influence, there was an increase in glomerular filtration and urinary excretion of creatinine and urea. It indicates the normalization of the kidney functional state and nitrogen metabolism. Moreover, this combination was significantly (p<0.05) superior to the Corvitin effect by the efficacy level.
Conclusions. In conditions of the end-stage renal failure in rats the injection combination of quercetin with N-acetylglucosamine was highly effective. It allows considering this combination to be a promising medicine for treating CKD at the IV-V stages. 


Keywords


quercetin; N-acetylglucosamine; glucosamine hydrochloride; end-stage renal failure; adenine-induced nephropathy

References


Lerma, E., Sparks, M., Topf, J. (2019). Nephrology Secrets, 4th edition. Philadelphia: Elsevier, 654.

Feehally, J., Floege, J., Johnson, R. J., Tonelli, M. (2019). Comprehensive Clinical Nephrology, 6th edition. Philadelphia: Elsevier, 1570.

Gilbert, S. J., Weiner, D. E. (2018). National Kidney Foundation’s Primer on Kidney Diseases, 7th edition. Philadelphia: Elsevier, 680.

Turner, N. N., Turner, N. N., Lameire, N., Goldsmith, D. J., Winearls, C. G., Himmelfarb, J., & Remuzzi, G. (Eds.). (2015). Oxford Textbook of Clinical Nephrology. Oxford Medicine Online. https://doi.org/10.1093/med/9780199592548.001.0001

Shebeko, S. K., Zupanets, I. A., Popov, O. S. Tarasenko, O. O., Shalamay, A. S. (2018). Effects of Quercetin and Its Combinations on Health. Polyphenols: Mechanisms of Action in Human Health and Disease, 2nd edition. London: Academic Press, 373–394.

Shebeko, S. K., Zupanets, I. A., Tarasenko, O. O. (2019). Nephroprotective effect of N-acetylglucosamine in rats with acute kidney injury. Česká a slovenská farmacie, 68(4), 173–179.

Shebeko, S. K., Zupanets, I. A., Popov, O. S. (2019). N-Acetylglucosamine is the most effective glucosamine derivative for the treatment of membranous nephropathy in rats. Pharmazie, 74(11), 667–670.

Shebeko, S. K., Zupanets, I. A., Propisnova, V. V. (2020). N-acetylglucosamine increases the efficacy of quercetin in the treatment of experimental acute kidney injury. Journal of Pharmacy & Pharmacognosy Research, 8(1), 53–63.

Guide for the care and use of laboratory animals, 8th edition. (2011). Washington : The National Academies Press, 246.

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 (2010). Official Journal of the European Union, L276, 33–79.

Kashioulis, P., Lundgren, J., Shubbar, E., Nguy, L., Saeed, A., Guron, C. W., & Guron, G. (2018). Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction. Kidney and Blood Pressure Research, 43(4), 1053–1064. https://doi.org/10.1159/000491056

Kamyshnikov, V. S. (2016). Metody klinicheskikh laboratornykh issledovanii. Moscow: MEDpress–inform, 736.

Islam, M. A., Al-Shiha, A. (2018). Foundations of Biostatistics. Singapore: Springer, 474.

Yang, H., Song, Y., Liang, Y., & Li, R. (2018). Quercetin Treatment Improves Renal Function and Protects the Kidney in a Rat Model of Adenine-Induced Chronic Kidney Disease. Medical Science Monitor, 24, 4760–4766. https://doi.org/10.12659/msm.909259

Layal, K., Perdhana, I. S., Louisa, M., Estuningtyas, A., & Soetikno, V. (2017). The effects of quercetin on oxidative stress and fibrosis markers in chronic kidney disease rat model. Medical Journal of Indonesia, 26(3), 169–177. https://doi.org/10.13181/mji.v26i3.1462

Vargas, F., Romecín, P., García-Guillén, A. I., Wangesteen, R., Vargas-Tendero, P., Paredes, M. D., … García-Estañ, J. (2018). Flavonoids in Kidney Health and Disease. Frontiers in Physiology, 9. https://doi.org/10.3389/fphys.2018.00394

Park, J., Lee, S.-Y., Ooshima, A., Yang, K.-M., Kang, J. M., Kim, Y.-W., & Kim, S.-J. (2013). Glucosamine hydrochloride exerts a protective effect against unilateral ureteral obstruction-induced renal fibrosis by attenuating TGF-β signaling. Journal of Molecular Medicine, 91(11), 1273–1284. https://doi.org/10.1007/s00109-013-1086-1

Hu, J., Chen, R., Jia, P., Fang, Y., Liu, T., Song, N., … Ding, X. (2017). Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats. Free Radical Biology and Medicine, 103, 121–132. https://doi.org/10.1016/j.freeradbiomed.2016.12.032

Fu, Y., Lin, Q., Gong, T., Sun, X., & Zhang, Z. (2016). Renal-targeting triptolide-glucosamine conjugate exhibits lower toxicity and superior efficacy in attenuation of ischemia/reperfusion renal injury in rats. Acta Pharmacologica Sinica, 37(11), 1467–1480. https://doi.org/10.1038/aps.2016.44

Baynes, J. W., Dominiczak, M. H. (2019). Medical Biochemistry, 5th edition. Philadelphia: Elsevier, 712.


GOST Style Citations


1. Lerma, E. Nephrology Secrets / E. Lerma, M. Sparks, J. Topf. – 4th еd. – Philadelphia : Elsevier, 2019. – 654 р.


2. Comprehensive Clinical Nephrology / J. Feehally, J. Floege, R. J. Johnson, M. Tonelli. – 6th ed. – Philadelphia : Elsevier, 2019. – 1570 р.


3. National Kidney Foundation’s Primer on Kidney Diseases / S. J. Gilbert, D. E. Weiner. – 7th ed. – Philadelphia : Elsevier, 2018. – 680 р.


4. Oxford Textbook of Clinical Nephrology / N. Turner, N. Lameire, D. J. Goldsmith et al. – 4th ed. – Oxford : Oxford University Press, 2016. – 3012 р. https://doi.org/10.1093/med/9780199592548.001.0001


5. Effects of Quercetin and Its Combinations on Health / S. K. Shebeko, I. A. Zupanets, O. S. Popov et al. // Polyphenols: Mechanisms of Action in Human Health and Disease. – 2nd ed. – London : Academic Press, 2018. – Р. 373–394.


6. Shebeko, S. K. Nephroprotective effect of N-acetylglucosamine in rats with acute kidney injury / S. K. Shebeko, I. A. Zupanets, O. O. Tarasenko // Česká a slovenská farmacie. – 2019. – Vol. 68 (4). – P. 173–179.


7. Shebeko, S. K. N-Acetylglucosamine is the most effective glucosamine derivative for the treatment of membranous nephropathy in rats / S. K. Shebeko, I. A. Zupanets, O. S. Popov // Pharmazie. – 2019. – Vol. 74 (11). – P. 667–670.


8. Shebeko, S. K. N-acetylglucosamine increases the efficacy of quercetin in the treatment of experimental acute kidney injury / S. K. Shebeko, I. A. Zupanets, V. V. Propisnova // J. of Pharmacy & Pharmacognosy Res. – 2020. – Vol. 8 (1). – P. 53–63.


9. Guide for the care and use of laboratory animals. – 8th ed. – Washington : The National Academies Press, 2011. – 246 p.


10. 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 // Official Journal of the European Union. – 2010. – Vol. L276. – Р. 33–79.

 

11. Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction / P. Kashioulis, J. Lundgren, E. Shubbar et al. // Kidney Blood Press. Res. – 2018. – Vol. 43 (4). – P. 1053–1064. https://doi.org/10.1159/000491056


12. Камышников, В. С. Методы клинических лабораторных исследований / В. С. Камышников. – 8-е изд. – М. : МЕДпресс-информ, 2016. – 736 с.


13. Islam, M. A. Foundations of Biostatistics / M. A. Islam, A. Al-Shiha. – Singapore : Springer, 2018. – 474 р.


14. Quercetin Treatment Improves Renal Function and Protects the Kidney in a Rat Model of Adenine-Induced Chronic Kidney Disease / H. Yang, Y. Song, Y. N. Liang, R. Li // Med. Sci. Monit. – 2018. – Vol. 24. – Р. 4760–4766. https://doi.org/10.12659/msm.909259


15. The effects of quercetin on oxidative stress and fibrosis markers in chronic kidney disease rat model / K. Layal, I. S. Perdhana, M. Louisa et al. // Med. J. Indones. – 2017. – Vol. 26. – Р. 169–177. https://doi.org/10.13181/mji.v26i3.1462

 

16. Flavonoids in Kidney Health and Disease / F. Vargas, P. Romecín, A. I. García-Guillén et al. // Front. Physiol. – 2018. – Vol. 9. – Article ID 394. https://doi.org/10.3389/fphys.2018.00394


17. Glucosamine hydrochloride exerts a protective effect against unilateral ureteral obstruction-induced renal fibrosis by attenuating TGF-β signaling / J. Park, S. Y. Lee, A. Ooshima et al. // J. Mol. Med. – 2013. – Vol. 91 (11). – Р. 1273–1284. https://doi.org/10.1007/s00109-013-1086-1


18. Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats / J. Hu, R. Chen, P. Jia et al. // Free Radic. Biol. Med. – 2017. – Vol. 103. – Р. 121–132. https://doi.org/10.1016/j.freeradbiomed.2016.12.032


19. Renal-targeting triptolide-glucosamine conjugate exhibits lower toxicity and superior efficacy in attenuation of ischemia/ reperfusion renal injury in rats / Y. Fu, Q. Lin, T. Gong et al. // Acta Pharmacol. Sin. – 2016. – Vol. 37. – P. 1467–1480. https://doi.org/10.1038/aps.2016.44


20. Baynes, J. W. Medical Biochemistry / J. W. Baynes, M. H. Dominiczak. – 5th ed. – Philadelphia : Elsevier, 2019. – 712 р.





Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Clin. pharm.

ISSN 2518-1572 (Online), ISSN 1562-725X (Print)