Ukr.Biochem.J. 2025; Volume 97, Issue 4, Jul-Aug, pp. 73-83

doi: https://doi.org/10.15407/ubj97.04.073

Extracellular matrix degradation products in the heart of rats with metabolic syndrome under chromium picolinate administration

O. Ye. Akimov1*, A. O. Mykytenko2, V. O. Kostenko1

1Department of Pathophysiology, Poltava State Medical University, Poltava, Ukraine;
*e-mail: o.akimov@pdmu.edu.ua;
2Department of Biological and Bioorganic Chemistry,
Poltava State Medical University, Poltava, Ukraine

Received: 22 May 2025; Revised: 24 July 2025;
Accepted: 12 September 2025; Available on-line: 17 September 2025

The populace of Ukraine shows a trend of increasing percentage of persons with obesity, complicated by metabolic syndrome (MetS), which causes damage to the heart extracellular matrix. According to recent studies chromium, picolinate (CrPIC) has the potential to attenuate lipid metabolism disorders and protect the extracellular matrix from degradation. The aim of this research was to estimate the blood lipid profile and the content of glycosaminoglycans, L-hydroxyproline and sialic acids in the heart of rats with simulated metabolic syndrome under Chromium picolinate administration. Mature male Wistar rats were divided into 4 groups of 6 animals each – control; metabolic syndrome induction; CrPIC administration; metabolic syndrome + CrPIC administration. Metabolic syndrome was reproduced by using a 20% fructose solution as the only source of water for 60 days. CrPIC was administered orally at a dose of 80 µg/kg daily for 60 days. The concentration of the heart extracellular matrix degradation proteins was determined spectrophotometrically in a 10% heart homogenate. CrPIC administration to healthy animals stimulated the accumulation of glycosaminoglycans chondroitin fraction in the rat heart. Metabolic syndrome modeling resulted in an increase in TG, TC and LDL-C blood levels, intensification of collagenolysis, degradation of glycoproteins and glycosaminoglycans with a predominance of the keratan-dermatan fraction. CrPIC administration to animals with metabolic syndrome reduced collagenolysis and glycoproteins degradation, changed the dominating fraction of glycosaminoglycans from keratan-dermatan to chondroitin in rat heart connective tissue indicating its potential to prevent cardiac tissue remodeling during metabolic syndrome.

Keywords: , , , , , ,


References:

  1. Chong B, Jayabaskaran J, Kong G, Chan YH, Chin YH, Goh R, Kannan S, Ng CH, Loong S, Kueh MTW, Lin C, Anand VV, Lee ECZ, Chew HSJ, Tan DJH, Chan KE, Wang JW, Muthiah M, Dimitriadis GK, Hausenloy DJ, Mehta AJ, Foo R, Lip G, Chan MY, Mamas MA, le Roux CW, Chew NWS. Trends and predictions of malnutrition and obesity in 204 countries and territories: an analysis of the Global Burden of Disease Study 2019. EClinicalMedicine. 2023;57:101850. PubMed, PubMed, CrossRef
  2. GBD 2021 US Obesity Forecasting Collaborators. National-level and state-level prevalence of overweight and obesity among children, adolescents, and adults in the USA, 1990-2021, and forecasts up to 2050. Lancet. 2024;404(10469):2278-2298. PubMed, PubMed, CrossRef
  3. Dereń K, Wyszyńska J, Nyankovskyy S, Nyankovska O, Yatsula M, Łuszczki E, Sobolewski M, Mazur A. Secular Trends of Underweight, Overweight, and Obesity in Children and Adolescents from Ukraine. Int J Environ Res Public Health. 2021;18(6):3302. PubMed, PubMed, CrossRef
  4. Chandrasekaran P, Weiskirchen R. The Role of Obesity in Type 2 Diabetes Mellitus-An Overview. Int J Mol Sci. 2024;25(3):1882. PubMed, PubMed, CrossRef
  5. Elagizi A, Kachur S, Carbone S, Lavie CJ, Blair SN. A Review of Obesity, Physical Activity, and Cardiovascular Disease. Curr Obes Rep. 2020;9(4):571-581. PubMed, CrossRef
  6. Olatunbosun PP, El Hunjul GN, Patel A, Abbas RH, Mody S, Masalha A, Mehta S, Rizwan S, Pareek A, Jain S, Parambat SBC. Heart failure in patients with metabolic syndrome X. Discoveries (Craiova). 2023;11(1):e162. PubMed, PubMed, CrossRef
  7. Bassiouni W, Ali MAM, Schulz R. Multifunctional intracellular matrix metalloproteinases: implications in disease. FEBS J. 2021;288(24):7162-7182. PubMed, CrossRef
  8. Jalil JE, Gabrielli L, Ocaranza MP, MacNab P, Fernández R, Grassi B, Jofré P, Verdejo H, Acevedo M, Cordova S, Sanhueza L, Greig D. New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review. Int J Mol Sci. 2024;25(8):4407. PubMed, PubMed, CrossRef
  9. Burr SD, Stewart JA Jr. Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice. Cells. 2021;10(3):557. PubMed, PubMed, CrossRef
  10. El-Wakf AM, El-Sawi MR, El-Nigomy HM, El-Nashar EM, Al-Zahrani NS, Alqahtani NG, Aldahhan RA, Eldken ZH. Fennel seeds extract prevents fructose-induced cardiac dysfunction in a rat model of metabolic syndrome via targeting abdominal obesity, hyperuricemia and NF-κβ inflammatory pathway. Tissue Cell. 2024;88:102385. PubMed, CrossRef
  11. Antar SA, Ashour NA, Marawan ME, Al-Karmalawy AA. Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. Int J Mol Sci. 2023;24(4):4004. PubMed, PubMed, CrossRef
  12. Qiu L, Sheng P, Wang X. Identification of Metabolic Syndrome-Related miRNA-mRNA Regulatory Networks and Key Genes Based on Bioinformatics Analysis. Biochem Genet. 2023;61(1):428-447. PubMed, CrossRef
  13. Moradi F, Kooshki F, Nokhostin F, Khoshbaten M, Bazyar H, Pourghassem Gargari B. A pilot study of the effects of chromium picolinate supplementation on serum fetuin-A, metabolic and inflammatory factors in patients with nonalcoholic fatty liver disease: A double-blind, placebo-controlled trial. J Trace Elem Med Biol. 2021;63:126659. PubMed, CrossRef
  14. Sundaram B, Aggarwal A, Sandhir R. Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats. J Trace Elem Med Biol. 2013;27(2):117-121. PubMed, CrossRef
  15. Amini MR, Sheikhhossein F, Djafari F, Jafari A, Djafarian K, Shab-Bidar S. Effects of chromium supplementation on oxidative stress biomarkers. Int J Vitam Nutr Res. 2023;93(3):241-251. PubMed, CrossRef
  16. Majewski M, Gromadziński L, Cholewińska E, Ognik K, Fotschki B, Juśkiewicz J. Dietary Effects of Chromium Picolinate and Chromium Nanoparticles in Wistar Rats Fed with a High-Fat, Low-Fiber Diet: The Role of Fat Normalization. Nutrients. 2022;14(23):5138. PubMed, PubMed, CrossRef
  17. Ricottini L, Basciani S, Spizzichini ML, de Mattia D, Coniglio-Iannuzzi Delle Noci M, Sorrentino S, Nordio M. The Effectiveness and Safety of a Nutraceutical Combination in Overweight Patients with Metabolic Syndrome. Nutrients. 2024;16(23):3977.
    PubMed, PubMed, CrossRef
  18. Mamikutty N, Thent ZC, Sapri SR, Sahruddin NN, Mohd Yusof MR, Haji Suhaimi F. The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. Biomed Res Int. 2014;2014:263897. PubMed, PubMed, CrossRef
  19. Sahin K, Tuzcu M, Orhan C, Sahin N, Kucuk O, Ozercan IH, Juturu V, Komorowski JR. Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin. Br J Nutr. 2013;110(2):197-205.
    PubMed, CrossRef
  20. El-Kafoury BMA, Bahgat NM, Abdel-Hady EA, Samad AAAE, Shawky MK, Mohamed FA. Impaired metabolic and hepatic functions following subcutaneous lipectomy in adult obese rats. Exp Physiol. 2019;104(11):1661-1677. PubMed, CrossRef
  21. Zhang Y, Wang R, Fu X, Song H. Non-insulin-based insulin resistance indexes in predicting severity for coronary artery disease. Diabetol Metab Syndr. 2022;14(1):191. PubMed, PubMed, CrossRef
  22. Mykytenko AО, Akimov OY, Yeroshenko GA, Neporada KS. Influence of doxorubicin on the extracellular matrix of the liver of rats under conditions of chronic alcoholic hepatitis. Regul Mech Biosyst. 2023;14(2):278-283. CrossRef
  23. Volpi N. Purification of heparin, dermatan sulfate and chondroitin sulfate from mixtures by sequential precipitation with various organic solvents. J Chromatogr B Biomed Appl. 1996;685(1):27-34. PubMed, CrossRef
  24. Kaidashev IP, editor. Methods of clinical and experimental research in medicine. Poltava: Polymet; 2003. p.137-139 (In Ukrainian).
  25. El-Sayed SS, Rezq S, Alsemeh AE, Mahmoud MF. Moxonidine ameliorates cardiac injury in rats with metabolic syndrome by regulating autophagy. Life Sci. 2023;312:121210.  PubMed, CrossRef
  26. Hayashida K, Aquino RS, Park PW. Coreceptor functions of cell surface heparan sulfate proteoglycans. Am J Physiol Cell Physiol. 2022;322(5):C896-C912. PubMed, PubMed, CrossRef
  27. Schultheis N, Becker R, Berhanu G, Kapral A, Roseman M, Shah S, Connell A, Selleck S. Regulation of autophagy, lipid metabolism, and neurodegenerative pathology by heparan sulfate proteoglycans. Front Genet. 2023;13:1012706. PubMed, PubMed, CrossRef
  28. de Sousa GF, Palmero CY, de Souza-Menezes J, Araujo AK, Guimarães AG, de Barros CM. Dermatan sulfate obtained from the Phallusia nigra marine organism is responsible for antioxidant activity and neuroprotection in the neuroblastoma-2A cell lineage. Int J Biol Macromol. 2020;164:1099-1111. PubMed, CrossRef
  29. Metschl S, Bruder L, Paloschi V, Jakob K, Reutersberg B, Reeps C, Maegdefessel L, Gee M, Eckstein HH, Pelisek J. Changes in Endocan and Dermatan Sulfate Are Associated with Biomechanical Properties of Abdominal Aortic Wall during Aneurysm Expansion and Rupture. Thromb Haemost. 2022;122(9):1513-1523. PubMed, CrossRef
  30. Pessentheiner AR, Ducasa GM, Gordts PLSM. Proteoglycans in Obesity-Associated Metabolic Dysfunction and Meta-Inflammation. Front Immunol. 2020;11:769. PubMed, PubMed, CrossRef
  31. Yan G, Fan M, Zhou Y, Xie M, Shi J, Dong N, Wang Q, Qiao W. Chondroitin Sulfate Derivative Cross-Linking of Decellularized Heart Valve for the Improvement of Mechanical Properties, Hemocompatibility, and Endothelialization. ACS Appl Mater Interfaces. 2024;16(28):35936-35948. PubMed, CrossRef
  32. Koch CD, Lee CM, Apte SS. Aggrecan in Cardiovascular Development and Disease. J Histochem Cytochem. 2020;68(11):777-795. PubMed, PubMed, CrossRef
  33. Liu T, Yu H, Wang S, Li H, Du X, He X. Chondroitin sulfate alleviates osteoporosis caused by calcium deficiency by regulating lipid metabolism. Nutr Metab (Lond). 2023;20(1):6. PubMed, PubMed, CrossRef
  34. Poznyak AV, Kashirskikh DA, Postnov AY, Popov MA, Sukhorukov VN, Orekhov AN. Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis. Braz J Med Biol Res. 2023;56:e12972. PubMed, PubMed, CrossRef
  35. Al-Roub A, Akhter N, Al-Rashed F, Wilson A, Alzaid F, Al-Mulla F, Sindhu S, Ahmad R. TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/ERK/NF-kB signaling pathways. Sci Rep. 2023;13(1):14351. PubMed, PubMed, CrossRef
  36. Gossa Al-Saadde DL, Haider AM, Ali A, Abdu Musad Saleh E, Turki Jalil A, Abdulelah FM, Romero-Parra RM, Tayyib NA, Ramírez-Coronel AA, Alkhayyat AS. The role of chromium supplementation in cardiovascular risk factors: A comprehensive reviews of putative molecular mechanisms. Heliyon. 2023;9(9):e19826. PubMed, PubMed, CrossRef
  37. Hejazian SM, Hosseiniyan Khatibi SM, Barzegari A, Pavon-Djavid G, Razi Soofiyani S, Hassannejhad S, Ahmadian E, Ardalan M, Zununi Vahed S. Nrf-2 as a therapeutic target in acute kidney injury. Life Sci. 2021;264:118581. PubMed, CrossRef
  38. Ibrahim MA, Isah MB, Inim MD, Abdullahi AD, Adamu A. The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value? Glycobiology. 2024;34(9):cwae053. PubMed, CrossRef
  39. Li X, Zhang W. Tumor necrosis factor-α promotes osteoclast differentiation via sialylation in mice. Nan Fang Yi Ke Da Xue Xue Bao. 2021;41(12):1773-1779. PubMed, PubMed, CrossRef
  40. Karhadkar TR, Meek TD, Gomer RH. Inhibiting Sialidase-Induced TGF- β 1 Activation Attenuates Pulmonary Fibrosis in Mice. J Pharmacol Exp Ther. 2021;376(1):106-117. PubMed, PubMed, CrossRef
  41. Akimov OYe, Mykytenko AO, Mischenko AV, Kostenko VO. Effect of chromium picolinate on intensity of extracellular matrix degradation in biceps femoris muscle of rats during metabolic syndrome modelling. Actual Probl Modern Med Bull Ukr Med Stomatol Acad. 2025;25(1):97-101. CrossRef
  42. Panchal SK, Wanyonyi S, Brown L. Selenium, Vanadium, and Chromium as Micronutrients to Improve Metabolic Syndrome.
    Curr Hypertens Rep. 2017;19(3):10. PubMed, CrossRef
  43. Chen S, Zhou L, Guo Q, Fang C, Wang M, Peng X, Yin J, Li S, Zhu Y, Yang W, Zhang Y, Shan Z, Chen X, Liu L. Association of plasma chromium with metabolic syndrome among Chinese adults: a case-control study. Nutr J. 2020;19(1):107. PubMed, PubMed, CrossRef
  44. Pingali U, Nutalapati C, Gundagani S. Effect of Omega-3 Fatty Acid Alone and in Combination with Proprietary Chromium Complex on Endothelial Function in Subjects with Metabolic Syndrome: A Randomized, Double-Blind, Parallel-Group Clinical Study. Evid Based Complement Alternat Med. 2021;2021:2972610. PubMed, PubMed, CrossRef

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