JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2020, 69(5):222-229 | DOI: 10.36290/csf.2020.031

The hepatoprotective effect of the combination of glucosamine derivatives with quercetin against methotrexate-induced liver toxicity

Kateryna V. Vietrova*, Igor A. Zupanets, Tatiana S. Sakharova
Department of Clinical Pharmacology and Clinical Pharmacy, National University of Pharmacy, Kharkiv, Ukraine

The article presents the results of the study of the combination of aminosugars - glucosamine hydrochloride (GA h/ch) and N-acetylglucosamine - with quercetin (Q) called GlukvamineTM as a corrector of hepatotoxicity induced by methotrexate (MTX). The study was conducted on a model of MTX-induced liver damage in rats. GlukvamineTM was studied in the dose of 82 mg/kg with daily intragastric administration for 10 days compared to the substance GA h/ch, which was administered intragastrically at a dose of 50 mg/kg, and the substance of Q, which was administered intragastrically in the dose of 20.5 mg/kg. The efficiency of the drugs was assessed by the general condition of the animals, the values of the liver mass coefficient, the biochemical parameters of the blood serum and the histological analysis of the liver tissue. The GlukvamineTM effect on rats with MTX-induced liver damage caused an improvement of their general condition, recovery of the functional state of the liver by biochemical indicators, and the results of the histological analysis indicated a decrease in hepatotoxicity of MTX. At the same time, GlukvamineTM has statistically significantly exceeded the effect of GA h/ch and Q by most parameters. Thus, GlukvamineTM is a promising effective and safe drug for pharmacological correction of the hepatotoxicity of MTX.

Keywords: glucosamine; quercetin; GlukvamineTM; hepatoprotective effect; Methotrexate

Received: October 20, 2020; Accepted: December 2, 2020; Published: May 1, 2020  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Vietrova KV, Zupanets IA, Sakharova TS. The hepatoprotective effect of the combination of glucosamine derivatives with quercetin against methotrexate-induced liver toxicity. Čes. slov. farm. 2020;69(5-6):222-229. doi: 10.36290/csf.2020.031.
Download citation

References

  1. EMA/414775/2019. New measures to avoid potentially fatal dosing errors with methotrexate for inflammatory diseases. https://www.ema.europa.eu(23.08.2019).
  2. Mohammad K. Z., Tooba S., Syed S. A., Haseeb A., Fahim H. K. Understanding the binding interaction between methotrexate and human alpha-2-macroglobulin: Multi-spectroscopic and computational investigation. Archives of Biochemistry and Biophysics 2019; 675, Article 108118. https://www.sciencedirect.com. Go to original source... Go to PubMed...
  3. LiverTox: Clinical and research information on drug induced liver injury. methotrexate. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.ncbi.nlm.nih.gov/books/NBK548219/(19.02.2020).
  4. Fouad A. A., Hafez H. M., Hamouda A. Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity. Hum. Exp. Toxicol. 2020; 39(1), 77-85. Go to original source... Go to PubMed...
  5. Hoshyar R., Sebzari A., Balforoush M., Valavi M., Hosseini M. The impact of Crocus sativus stigma against methotrexate-induced liver toxicity in rats. J. Complement. Integr. Med. 2019; 17(2), Article 20190201. https://www.degruyter.com Go to original source... Go to PubMed...
  6. Hempfling W., Dilger K., Beuers U. Systematic review: ursodeoxycholic acid - adverse effects and drug interaction. Aliment. Pharmacol. Ther. 2003; 18(10), 963-972. Go to original source... Go to PubMed...
  7. Zupanets K. O. The experimental foundation of the combined application of glucosamine derivatives with quercetine in different variants of osteoarthritis. Kharkiv: Ph.D. Thesis 2011, 183 p (in Ukrainian).
  8. Seyed H. M., Elham B., Azar H., Khadijeh J. Protective effects of glucosamine and its acetylated derivative on serum/glucose deprivation-induced PC12 cells death: Role of reactive oxygen species. Res. Pharm. Sci. 2018; 13(2), 121-129. Go to original source... Go to PubMed...
  9. El-Horany H. E., El-Latif R. N., ElBatsh M. M., Emam M. N. Ameliorative effect of quercetin on neurochemical and behavioral deficits in rotenone rat model of Parkinson's disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease). J. Biochem. Mol. Toxicol. 2016; 30(7), 360-369. Go to original source... Go to PubMed...
  10. Tahia H. S., Nagwa A. E., Mohammed H. H., Nahed A. M., Nashwa A. M. M., Emaad A., Azza S. T. Comparative protective effects of n-acetylcysteine, N-acetyl methionine, and N-acetyl gucosamine against pracetamol and phenacetin therapeutic doses-induced hepatotoxicity in Rats. Int. J. Hepatol. 2018; 2018, Article 7603437. https://www.hindawi.com Go to original source... Go to PubMed...
  11. Ying-Jen C., Yuahn-Sieh H., Jiann-Torng C., Yi-Hao C., Ming-Cheng T., Ching-Long C., Chang-Min L. Protective effects of glucosamine on oxidative-stress and ischemia/reperfusion-induced retinal injury. Investig. Ophthalmol. Vis. Sci. 2015; 56, 1506-1516. Go to original source... Go to PubMed...
  12. Fernández-Palanca P., Fondevila F., Méndez-Blanco C., Tuñón M. J., González-Gallego J., Mauriz J. L. Antitumor effects of quercetin in hepatocarcinoma in vitro and in vivo models: a systematic review. Nutrients 2019; 11, Article 2875. https://www.mdpi.com/journal/nutrients Go to original source... Go to PubMed...
  13. Wei C. B., Zhou L. D., Zhang J. W., Zhang Q. H., Tao K. Protective effects of quercetin against the triptolide induced liver injury and relevant mechanism study. Sichuan Da Xue Xue Bao Yi Xue Ban 2019; 50(5), 684-687 (in Chinese).
  14. Zohreh S. H., Azita A., Leila J., Farzad S. Effect of quercetin on oxidative stress and liver function in beta-thalassemia major patients receiving desferrioxamine: A double-blind randomized clinical trial. J. Res. Med. Sci. 2019; 24, Article 91. https://www.jmsjournal.net Go to original source... Go to PubMed...
  15. Haleagrahara N., Hodgson K., Miranda-Hernandez S., Hughes S., Kulur A. B., Ketheesan N. Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis. Inflammopharmacology 2018; 26(5), 1219-1232. Go to original source... Go to PubMed...
  16. Eman E. B., Kamal M. M. The possible protective effect of quercetin on methotrexate induced hepatotoxicity in albino rats: biochemical, histological and immunohistochemical study. Egyptian Journal of Histology 2019; 43(1), 220-229.
  17. Vietrova K. V. Experimental evidance of the expediency of correction of the toxic effects of anticancer drugs by derivatives of glucosamine and their combination with quercetin. Kharkiv: Ph.D. Thesis 2015 (in Ukrainian).
  18. Guide for the care and use of laboratory animals, 8th ed. Washington: National Academies Press 2011.
  19. Sharp P., Villano J. S. The laboratory rat, 2nd ed. Boca Raton: CRC Press 2013. Go to original source...
  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. Official Journal of the European Union 2010; L276, 33-79.
  21. Zupanets I. A. Experimental rationale for the use of glucosamine and its derivatives in medicine. M.D. Thesis, Kupavna, 1993 (in Russian).
  22. Vardi N., Parlakpinar H., Cetin A., et al. Protective effect of β-carotene on methotrexate-induced oxidative liver damage. Toxicologic. Pathology 2010; 38, 592-597. Go to original source... Go to PubMed...
  23. Flecknell P. A. Laboratory animal anesthesia, 4th ed. Oxford: Academic Press 2015.
  24. Stefanov O. V. Preclinical studies of drugs. Kiev: Avicenna 2001 (in Ukrainian).
  25. Devasagayam T. P. A., Boloor K. K., Ramasarma T. Methods for estimating lipid peroxidation: An analysis of merits and demerits. Indian Journal of Biochemistry & Biophysics 2003; 40, 300-308.
  26. Rebrova O. Yu. Statistical analysis of medical data. Application of the STATISTIKA software package, 3rd ed. Moscow: Media Sphere 2006 (in Russian).
  27. Alexander V. A. D., Namani S., Subramani P., Sengodan B., Radhakrishnan A. Ameliorative Effect of Quercetin on Methotrexate Induced Toxicity in Sprague-Dawley Rats: A Histopathological Study. Indian J. Pharm. Educ. 2016; 50(3), S200-S208. Go to original source...
  28. Erdogan E., Ilgaz Y., Gurgor P. N., Oztas Y., Topal T., Oztas E. Rutin ameliorates methotrexate induced hepatic injury in rats. Acta Cir. Bras. 2015; 30(11), 778-784. Go to original source... Go to PubMed...
  29. Bhakti A. M., Thankamani M. Protective effect of Morinda citrifolia L. (fruit extract) on methotrexate-induced toxicities - hematological and biochemical studies. Cogent Biology 2016; 2, Article 1207879. https://www.cogentoa.com Go to original source...
  30. Kumari S. Methotrexate Induced Hepatotoxicity and its Management. Int. J. Sci. Res. 2016; 5(9), 1477-1481.
  31. Cao Y., Shi H., Sun Z., Wu J., Xia Y., Wang Y., Wu Y., Li X., Chen W., Wang A., Lu Y. Protective Effects of Magnesium Glycyrrhizinate on Methotrexate-Induced Hepatotoxicity and Intestinal Toxicity May Be by Reducing COX-2. Front. Pharmacol. 2019; 10, Article 119. https://www.frontiersin.org Go to original source... Go to PubMed...




Czech and Slovak Pharmacy

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.