Hepatoprotective effects of chondroitin sulfate and glucosamine sulfate
Abstract
Background. Long-term use of chondroprotective agents – chondroitin sulfate (CS) and glucosamine sulfate (GS) in the treatment of osteoarthritis puts forward increased requirements for the safety of drugs, primarily in terms of effects on the liver and kidneys.
Objective: systematization of data on the effect of chondroprotectors on liver structure and functions.
Material and methods. Using the methods of the theory of topological text analysis, an intellectual analysis of 2319 publications on fundamental and clinical studies of the relationship of CS and GS with liver function was carried out. The search was performed by a key query “(chondroitine OR glucosamine) AND (liver OR hepatic OR hepatocy*)” in the PubMed/MEDLINE database.
Results. The systematic analysis indicated a pronounced hepatoprotective effect of CS and GS pharmaceutical substances with a high degree of purification from inorganic and organic impurities. By regulating inflammation processes, lymphocyte function, fat and carbohydrate metabolism in the liver, standardized forms of CS and GS have a beneficial effect on fat metabolism, reduce chronic inflammation in the liver, exhibit antitumor and pronounced hepatoprotective effects on various models of liver intoxication.
Conclusion. The results of this analysis allow us to assert the high safety of drugs based on pharmaceutical standardized forms of CS and GS in terms of liver function.
About the Authors
I. Yu. Torshin
Federal Research Center “Informatics and Management”, Russian Academy of Sciences
Russian Federation
Russian Federation
Ivan Yu. Torshin – PhD (Phys. Math.), PhD (Chem.), Senior Researcher
WoS ResearcherID: C-7683-2018
Scopus Author ID: 7003300274
RSCI SPIN-code: 1375-1114
4 Vavilov Str., Moscow 119333
A. M. Lila
Nasonov Research Institute of Rheumatology
Russian Federation
Russian Federation
Aleksandr M. Lila – Dr. Med. Sc., Professor, Director
WoS ResearcherID: W-3334-2017
Scopus Author ID: 6602550827
RSCI SPIN-code: 7287-8555
34А Kashirskoye Hwy, Moscow 115522
O. A. Gromova
Federal Research Center “Informatics and Management”, Russian Academy of Sciences
Russian Federation
Russian Federation
Olga A. Gromova – Dr. Med. Sc., Professor, Research Supervisor
WoS ResearcherID: J-4946-2017
Scopus Author ID: 7003589812
RSCI SPIN-code: 6317-9833
4 Vavilov Str., Moscow 119333
References
1. Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019; 15 (5): 288–98. https://doi.org/10.1038/s41574-019- 0176-8.
2. Reginato A.M., Riera H., Vera M., et al. Osteoarthritis in Latin America: study of demographic and clinical characteristics in 3040 patients. J Clin Rheumatol. 2015; 21(8): 391–7. https://doi.org/10.1097/ RHU.0000000000000281.
3. Bruyère O., Honvo G., Veronese N., et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019; 49 (3): 337–50. https://doi.org/10.1016/j. semarthrit.2019.04.008.
4. Torshin I.Yu., Lila A.M., Limanova O.A., Gromova O.A. Prospects for the use of chondroitin sulfate and glucosamine sulfate in osteoarthritis in combination with pathology of the kidneys and urinary system. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / PHARMACOECONOMICS. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (1): 23–34 (in Russ.). https://doi.org/10.17749/2070-4909.2020.13.1.23-34.
5. Raksasuk S., Ungprasert P. Patients with rheumatoid arthritis have an increased risk of incident chronic kidney disease: a systematic review and meta-analysis of cohort studies. Int Urol Nephrol. 2020; 52 (1): 147–54. https://doi.org/10.1007/s11255-019-02346-4.
6. Jóźwiak-Bebenista M., Nowak J.Z. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm. 2014; 71 (1): 11–23.
7. Machado G.C., Maher C.G., Ferreira P.H., et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015; 350: h1225. https://doi.org/10.1136/bmj.h1225.
8. Bourhia M., Ullah R., Alqahtani A.S., Ibenmoussa S. Evidence of drug-induced hepatotoxicity in the Maghrebian population. Drug Chem Toxicol. 2020: 1–5. https://doi.org/10.1080/01480545.2020.1 797088.
9. Kwon J., Kim S., Yoo H., Lee E. Nimesulide-induced hepatotoxicity: a systematic review and meta-analysis. PLoS One. 2019; 14 (1): e0209264. https://doi.org/10.1371/journal.pone.0209264.
10. Lila A.M., Torshin I.Yu., Gromova O.A. Is it worth rethinking the positive experience of using chondroitin sulfates in atherosclerosis obtained half a century ago? FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / PHARMACOECONOMICS. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (2): 184–91 (in Russ.). https://doi.org/10.17749/2070-4909/ farmakoekonomika.2020.043.
11. Gromova O.A., Torshin I.Yu., Lila A.M., et al. On the safety of glucosamine sulfate in patients with insulin resistance. Consilium Medicum. 2019; 21 (4): 22–30 (in Russ.). https://doi.org/10.26442/20751753.2019.4.190309.
12. Torshin I.Yu., Rudakov K.V. On the theoretical basis of the metric analysis of poorly formalized problems of recognition and classification. Pattern Recognit Image Anal. 2015; 25 (4): 577–87.
13. Torshin I.Yu., Rudakov K.V. On the procedures of generation of numerical features over partitions of sets of objects in the problem of predicting numerical target variables. Pattern Recognit Image Anal. 2019; 29 (4): 654–67. https://dx.doi.org/10.1134/S1054661819040175.
14. Torshin I.Yu., Gromova O.A., Stakhovskaya L.V., et al. Analysis of 19.9 million publications from the Pubmed/MEDLINE database using artificial intelligence methods: approaches to the generalizations of accumulated data and the phenomenon of “fake news”. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (2): 146–63 (in Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.021.
15. Lila A.M., Gromova O.A., Torshin I.Yu., et al. Molecular effects of chondrogard in osteoarthritis and herniated discs. Neurology, Neuropsychiatry, Psychosomatics. 2017; 9 (3): 88–97 (in Russ.). http://dx.doi.org/10.14412/2074-2711-2017-3-88-97.
16. Luo J., Zhang Z., Zeng Y., et al. Co-encapsulation of collagenase type I and silibinin in chondroitin sulfate coated multilayered nanoparticles for targeted treatment of liver fibrosis. Carbohydr Polym. 2021; 263: 117964. https://doi.org/10.1016/j.carbpol.2021.117964.
17. Luo J., Gong T., Ma L. Chondroitin-modified lipid nanoparticles target the Golgi to degrade extracellular matrix for liver cancer management. Carbohydr Polym. 2020; 249: 116887. https://doi.org/10.1016/j.carbpol.2020.116887.
18. Vallières M., du Souich P. Modulation of inflammation by chondroitin sulfate. Osteoarthritis Cartilage. 2010; 18 (Suppl. 1): S1–6. https://doi.org/10.1016/j.joca.2010.02.017.
19. Li S., Jiang W., Hu S., et al. Fucosylated chondroitin sulphate from Cusumaria frondosa mitigates hepatic endoplasmic reticulum stress and inflammation in insulin resistant mice. Food Funct. 2015; 6 (5): 1547–56. https://doi.org/10.1039/c4fo01153h.
20. Panicker S., Borgia J., Fhied C., et al. Oral glucosamine modulates the response of the liver and lymphocytes of the mesenteric lymph nodes in a papain-induced model of joint damage and repair. Osteoarthritis Cartilage. 2009; 17 (8): 1014–21. https://doi.org/10.1016/j.joca.2009.01.011.
21. Hao X., Li Y., Wang J., et al. Deficient O-GlcNAc glycosylation impairs regulatory T cell differentiation and Notch signaling in autoimmune hepatitis. Front Immunol. 2018; 9: 2089. https://doi.org/10.3389/fimmu.2018.02089.
22. Hwang J.S., Kim K.H., Park J., et al. Glucosamine improves survival in a mouse model of sepsis and attenuates sepsis-induced lung injury and inflammation. J Biol Chem. 2019; 294 (2): 608–22. https://doi.org/10.1074/jbc.RA118.004638.
23. Caramés B., Kiosses W.B., Akasaki Y., et al. Glucosamine activates autophagy in vitro and in vivo. Arthritis Rheum. 2013; 65 (7): 1843–52. https://doi.org/10.1002/art.37977.
24. Olsson U., Egnell A.C., Lee M.R., et al. Changes in matrix proteoglycans induced by insulin and fatty acids in hepatic cells may contribute to dyslipidemia of insulin resistance. Diabetes. 2001; 50 (9): 2126–32. https://doi.org/10.2337/diabetes.50.9.2126.
25. Kiran G., Prasada Rao U.J., Salimath P.V., Chilkunda N.D. Dietinduced hypercholesterolemia alters liver glycosaminoglycans and associated-lipoprotein receptors in rats. J Physiol Biochem. 2017; 73 (4): 539–50. https://doi.org/10.1007/s13105-017-0583-z.
26. Seol B.G., Kim J.H., Woo M., et al. Skate cartilage extracts containing chondroitin sulfate ameliorates hyperlipidemia-induced inflammation and oxidative stress in high cholesterol diet-fed LDL receptor knockout mice in comparison with shark chondroitin sulfate. Nutr Res Pract. 2020; 14 (3): 175–87. https://doi.org/10.4162/nrp.2020.14.3.175.
27. Huang L., Chen J., Cao P., et al. Anti-obese effect of glucosamine and chitosan oligosaccharide in high-fat diet-induced obese rats. Mar Drugs. 2015; 13 (5): 2732–56. https://doi.org/10.3390/md13052732.
28. Li W., Kobayashi T., Moroi S., et al. Anti-obesity effects of chondroitin sulfate oligosaccharides from the skate Raja pulchra. Carbohydr Polym. 2019; 214: 303–10. https://doi.org/10.1016/j.carbpol.2019.03.025.
29. Han L.K., Sumiyoshi M., Takeda T., et al. Inhibitory effects of chondroitin sulfate prepared from salmon nasal cartilage on fat storage in mice fed a high-fat diet. Int J Obes Relat Metab Disord. 2000; 24 (9): 1131–8. https://doi.org/10.1038/sj.ijo.0801378.
30. Zhu Q., Lin L., Zhao M. Sulfated fucan/fucosylated chondroitin sulfate-dominated polysaccharide fraction from low-edible-value sea cucumber ameliorates type 2 diabetes in rats: new prospects for sea cucumber polysaccharide based-hypoglycemic functional food. Int J Biol Macromol. 2020; 159: 34–45. https://doi.org/10.1016/j.ijbiomac.2020.05.043.
31. Wu N., Zhang Y., Ye X., et al. Sulfation pattern of fucose branches affects the anti-hyperlipidemic activities of fucosylated chondroitin sulfate. Carbohydr Polym. 2016; 147: 1–7. https://doi.org/10.1016/j.carbpol.2016.03.013.
32. Hu S.W., Tian Y.Y., Chang Y.G., et al. Fucosylated chondroitin sulfate from sea cucumber improves glucose metabolism and activates insulin signaling in the liver of insulin-resistant mice. J Med Food. 2014; 17 (7): 749–57. https://doi.org/10.1089/jmf.2013.2924.
33. Chen T.Y., Sun D., Lin W.S., et al. Glucosamine regulation of fibroblast growth factor 21 expression in liver and adipose tissues. Biochem Biophys Res Commun. 2020; 529 (3): 714–9. https://doi.org/10.1016/j.bbrc.2020.06.070.
34. Barrientos C., Racotta R., Quevedo L. Glucosamine attenuates increases of intraabdominal fat, serum leptin levels, and insulin resistance induced by a high-fat diet in rats. Nutr Res. 2010; 30 (11): 791–800. https://doi.org/10.1016/j.nutres.2010.10.008.
35. Phoomak C., Vaeteewoottacharn K., Silsirivanit A., et al. High glucose levels boost the aggressiveness of highly metastatic cholangiocarcinoma cells via O-GlcNAcylation. Sci Rep. 2017; 7: 43842. https://doi.org/10.1038/srep43842.
36. Lv H., Yu G., Sun L., et al. Elevate level of glycosaminoglycans and altered sulfation pattern of chondroitin sulfate are associated with differentiation status and histological type of human primary hepatic carcinoma. Oncology. 2007; 72 (5–6): 347–56. https://doi.org/10.1159/000113145.
37. Wang Y., Liu G., Liu R., et al. EPS364, a novel deep-sea bacterial exopolysaccharide, inhibits liver cancer cell growth and adhesion. Mar Drugs. 2021; 19 (3): 171. https://doi.org/10.3390/md19030171.
38. Zhang L., Liu W.S., Han B.Q., et al. Antitumor activities of D-glucosamine and its derivatives. J Zhejiang Univ Sci B. 2006; 7 (8): 608–14. https://doi.org/10.1631/jzus.2006.B0608.
39. Ryanto G.R.T., Yorifuji K., Ikeda K., Emoto N. Chondroitin sulfate mediates liver responses to injury induced by dual endothelin receptor inhibition. Can J Physiol Pharmacol. 2020; 98 (9): 618–24. https://doi.org/10.1139/cjpp-2019-0649.
40. Nagano F., Mizuno T., Mizumoto S., et al. Chondroitin sulfate protects vascular endothelial cells from toxicities of extracellular histones. Eur J Pharmacol. 2018; 826: 48–55. https://doi.org/10.1016/j.ejphar.2018.02.043.
41. Song Y.O., Kim M., Woo M., et al. Chondroitin sulfate-rich extract of skate cartilage attenuates lipopolysaccharide-induced liver damage in mice. Mar Drugs. 2017; 15 (6): 178. https://doi.org/10.3390/md15060178.
42. Campo G.M., Avenoso A., Campo S., et al. The antioxidant activity of chondroitin-4-sulphate, in carbon tetrachloride-induced acute hepatitis in mice, involves NF-kappaB and caspase activation. Br J Pharmacol. 2008; 155 (6): 945–56. https://doi.org/10.1038/bjp.2008.338.
43. Ha B.J., Lee J.Y. The effect of chondroitin sulfate against CCl4- induced hepatotoxicity. Biol Pharm Bull. 2003; 26 (5): 622–6. https://doi.org/10.1248/bpb.26.622.
44. Parise E.R., Chehter L., Nogueira M.D., et al. Effects of vitamin A administration on collagen and sulfated glycosaminoglycans contents in the livers of rats treated with carbon tetrachloride. J Lab Clin Med. 1992; 119 (6): 676–81.
45. Sal'nikova S.I., Drogovoz S.M., Zupanets I.A. The liver-protective properties of D-glucosamine. Farmakol Toksikol. 1990; 53 (4): 33–5.
46. Vietrova K.V., Zupanets I.A., Sakharova T.S. The hepatoprotective effect of the combination of glucosamine derivatives with quercetin against methotrexate-induced liver toxicity. Ceska Slov Farm. 2020; 69 (5–6): 222–9.
47. Qinna N.A., Shubbar M.H., Matalka K.Z., et al. Glucosamine enhances paracetamol bioavailability by reducing its metabolism. J Pharm Sci. 2015; 104 (1): 257–65. https://doi.org/10.1002/jps.24269.
48. Gromova O.A., Torshin I.Yu., Maiorova L.A., et al. Bioinformatic and chemoneurocytological analysis of the pharmacological properties of vitamin B12 and some of its derivatives. J Porph Phthal. 2021; 25 (9): 835–42. https://doi.org/10.1142/S1088424621500644.
49. Gromova O.A., Torshin I.Yu., Zaichik B.Ts., et al. Differences in the standardization of medicinal products based on extracts of chondroitin sulfate. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / PHARMACOECONOMICS. Modern Pharmacoeconomics and Pharmacoepidemiology. 2021; 14 (1): 40–52. https://doi.org/10.17749/2070-4909/farmakoekonomika.2021.083.
50. Torshin I.Yu., Lila A.M., Naumov A.V., et al. Meta-analysis of clinical trials of osteoarthritis treatment effectiveness with Chondroguard. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (4): 18–29 (in Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.066.
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Supporting agencies: This work was financially supported by the grant of the Russian Science Foundation (No. 20-12-00175) in Ivanovo State University of Chemistry and Technology.
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Torshin I.Yu., Lila A.M., Gromova O.A. Hepatoprotective effects of chondroitin sulfate and glucosamine sulfate. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2021;14(4):537-547. (In Russ.) https://doi.org/10.17749/2070-4909/farmakoekonomika.2021.112
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