Protective Effects of Chitosan Nanogels Loaded with Vancomycin against Oxidative Stress and Hepatotoxicity Induces by Methicillin-resistant Staphylococcus aureus (MRSA)

الموضوعات :

Sahar Arkia ¹ , Javad Arasteh ² , Ardeshir Hesampoor ³ , Ali Esrafily ⁴

1 - Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
2 - Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
3 - Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
4 - Department of Environmental Health Engineering, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

تاريخ الإرسال : 04 الخميس , صفر, 1446 تاريخ التأكيد : 10 الإثنين , رمضان, 1446 تاريخ الإصدار : 21 السبت , شوال, 1446

الکلمات المفتاحية: MRSA, Chitosan nanogels loaded with Vancomycin, Hepatotoxicity, Lipid peroxidation,

ملخص المقالة :

Methicillin-resistant Staphylococcus aureus (MRSA) has also become one of the significant clinical and epidemiological issues in hospital environments. S. aureus spreads the bacteria to liver tissue, brain tissue, heart tissue, lung tissue, spleen or kidney tissues. Oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and super-oxide dismutase (SOD) activity were studied from liver tissue. Besides, histopathological examination of liver tissues plasma levels of inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured, as well as ALT (alanine aminotransferase) and AST (aspartate aminotransferase). The results provided were that MRSA toxicity brings about dose-dependent cell death and inflammation in the liver. Oxidative stress markers also increased by MRSA-infectious treatment (10⁶ CFU, 50 µl). Pro-inflammatory cytokines were also found that are implicated in inflammation and tissue damage. In addition, Chitosan nanogels encapsulating Vancomycin (100 mg kg^-1) treatment indicated reduced liver inflammation, plasma AST, ALT activity and oxidative damage compared to OTA group (p<0.001). On the whole, the findings of the study reveal that Chitosan nanogels encapsulating Vancomycin has strong antioxidant activity against inflammation and tissue damages exposed liver.

المصادر:

1. Hassoun A., P.K. Linden., 2017. Incidence, prevalence, and management of MRSA bacteremia across patient populations—a review of recent developments in MRSA management and treatment. Critical care. 21, 1-10.
2. Barrett J.F., 2005. MRSA–what is it, and how do we deal with the problem? Expert Opinion on Therapeutic Targets. 9, 253-265.
3. Balasubramanian D., Lamia H., 2017. Staphylococcus aureus pathogenesis in diverse host environments. Pathogens and disease. 75, ftx005.
4. Al-Mebairik N.F., EL-kersh T., 2016. A review of virulence factors, pathogenesis, and antibiotic resistance in Staphylococcus aureus. Reviews and Research in Medical Microbiology. 72, 50-56.
5. Fergestad M.E., Stamsås G.A., 2020. Penicillin‐binding protein PBP2a provides variable levels of protection toward different β‐lactams in Staphylococcus aureus RN4220. Microbiologyopen. 9(8), e1057.
6. Shalaby M.A.W., Dokla E.,Rabah.A.T S., 2020.Penicillin binding protein 2a: An overview and a medicinal chemistry perspective. European Journal of Medicinal Chemistry. 199, 112312.
7. Zhang L., X GU J., Langer R.,2008. Nanoparticles in medicine: therapeutic applications and developments. Clinical pharmacology & therapeutics. 83(5), 761-769.
8. Yetisgin A.A., Cetinel S., Zuvin M.,2020. Therapeutic nanoparticles and their targeted delivery applications. Molecules. 25(9), 2193.
9. Haleem A., Javaid M., Pratap Singh R., Suman R.,2023. Applications of nanotechnology in medical field: a brief review. Global Health Journal. 7(2), 70-77.
10. Roszek B., De Jong W.H., Geertsma R.E.,2005. Nanotechnology in medical applications: state-of-the-art in materials and devices.
11. Costa B., Alves P.M., Fonseca D.R., Monteiro A.C., Martins M.C.L., 2024. Dhvar5-chitosan nanogels and their potential to improve antibiotics activity. International Journal of Biological Macromolecules. 134059.
12. Asadi K., Heidari R., Hamidi M. Ommati M.M., Gholami A., Hashemzaei M , 2024.Trinitroglycerin-loaded chitosan nanogels: Shedding light on cytotoxicity, antioxidativity, and antibacterial activities. International Journal of Biological Macromolecules. 265, 130654.
13. Zhang Y.,Zhang J., Chen W., Angsantikul P., Zhang L., Gao W., 2017. Erythrocyte membrane-coated nanogel for combinatorial antivirulence and responsive antimicrobial delivery against Staphylococcus aureus infection. Journal of Controlled Release. 263,185-191.
14. Walvekar P., Gannimani R., Salih M., Makhathini S., Govender T.,2019.Self-assembled oleylamine grafted hyaluronic acid polymersomes for delivery of vancomycin against methicillin resistant Staphylococcus aureus (MRSA). Colloids and Surfaces B: Biointerfaces.182, 110388.
15. Hibbitts A., Lucía A., Matteis L.D., McArthur M.,2019 Co-delivery of free vancomycin and transcription factor decoy-nanostructured lipid carriers can enhance inhibition of methicillin resistant Staphylococcus aureus (MRSA). PLoS One. 14(9), 84.
16. Farag R.K., Mohamed R.R., 2013. Mohamed, Synthesis and characterization of carboxymethyl chitosan nanogels for swelling studies and antimicrobial activity. Molecules. 18(1), 190-203.
17. Li X., Hetjens L., Wolter N., Li H., Shi X., 2023.Charge-reversible and biodegradable chitosan-based microgels for lysozyme-triggered release of vancomycin. Journal of Advanced Research. 43, 87-96.
18. Rasool M., Malik M., Saleem S., 2019. Assessment of circulating biochemical markers in mice receiving cinnamon and glycyrrhizin under carbon tetrachloride induced hepatic injury. Proceedings of the National Academy of Sciences, India Section B: Biological Sciences. 89(1), 105-111.
19. Ray S., Chakraborty S., Pandit B., Das S., 2011.Cyclophosphamide-Induced Lipid Peroxidation and Changes in Cholesterol Content: Protective Role of Reduced Glutathione. Iranian Journal of Pharmaceutical Sciences. 7(4), 255-267.
20.Tang H., Long N., Lin L., Liu V.,Dai M., Sun F.,2018. Effect of MRSA on CYP450: dynamic changes of cytokines, oxidative stress, and drug-metabolizing enzymes in mice infected with MRSA. Infection and drug resistance. 229-238.
21. Shankar P., Prasanna kumar B.R., khallel M., 2011. Hepatoprotective Activity of Momordica diocia Roxb Fruits in CCl4-Induced Hepatotoxicity in Rats. Iranian Journal of Pharmaceutical Sciences. 7(4), 279-282.
22. Zhao C., Fan J.,Liu Y.,Guo W.,Cao H., Xiao J.,Wang Y.,2019.Hepatoprotective activity of Ganoderma lucidum triterpenoids in alcohol-induced liver injury in mice, an iTRAQ-based proteomic analysis. Food chemistry. 271, 148-156.
23. He Y., Xia Z.,Yu D., Wang G.,2019. Hepatoprotective effects and structure-activity relationship of five flavonoids against lipopolysaccharide/d-galactosamine induced acute liver failure in mice. International Immunopharmacology. 68, 171-178.
24. Karatayli E., 2020. Il-22 and Rantes upregulation in a new mouse model of bacterial infection related acute-on-chronic liver injury. Zeitschrift für Gastroenterologie. 2020. 58(01). 10.1055/s-0039-3402252.
25. He X., Lee H., Jin Y.,2020.Apoptotic Bodies Activate Macrophages and Promote Lung Inflammation in Septic Mice via AB-Containing MicroRNAs. American Journal of Respiratory and Critical Care Medicine. A5262-A526.
26. Chávez de Paz L.E., Resin A., Howard K.A., Wejse P.L.,2011.Antimicrobial effect of chitosan nanoparticles on Streptococcus mutans biofilms. Applied and Environmental Microbiology. 77(11), 3892-3895.
27. Aliasghari A., Khorasgani M.R., Vaezifar S.,Rahimi F.,Younesi H.,2016. Evaluation of antibacterial efficiency of chitosan and chitosan nanoparticles on cariogenic streptococci: An in vitro study. Iranian Journal of Microbiology. 8(2), 93.
28. Dey S., Bishayi B., 2015. Killing of Staphylococcus aureus in murine macrophages by chloroquine used alone and in combination with ciprofloxacin or azithromycin. Journal of Inflammation Research. 29-47.
29. Turner, M.D., Nedjai B., Hurst T., Pennington D.,2014. Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 1843(11), 2563-2582.
30. Popa C., Netea M.G., Stalenhoef A.F.,2007. The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. Journal of Lipid Research. 48(4), 751-762.
31. Nalos M., Nalos M., Parnell G.,Tang B., Nanan R., 2012. Immune effects of interferon gamma in persistent staphylococcal sepsis. American Journal of Respiratory and Critical Care Medicine. 185(1), 110-112.
32. Barin J.G.,Talor M.V., Schaub J.A., Diny N.L., Hou X., Hoyer M., Čiháková D., 2016. Collaborative interferon-γ and interleukin-17 signaling protects the oral mucosa from Staphylococcus aureus. The American Journal of Pathology. 186(9), 2337-2352.
33. Smith R.P., 2010.IFN-γ enhances killing of methicillin-resistant Staphylococcus aureus by human monocytes more effectively than GM-CSF in the presence of daptomycin and other antibiotics. Cytokine. 2010. 51(3), 274-277.
34. Kalhapure R.S., Jadhav M., Rambharose S., Mocktar C., Govender T., 2017. pH-responsive chitosan nanoparticles from a novel twin-chain anionic amphiphile for controlled and targeted delivery of vancomycin. international journal Colloids and Surfaces B . 650-657.







35. Karakeçili A., Topuz B., Korpayev S., Erdek M., 2019. Metal-organic frameworks for on-demand pH controlled delivery of vancomycin from chitosan scaffolds. Materials Science and Engineering. 105, 110098.
36. Mancuso G., Midiri A., Gerace E., Biondo C.,2021. Bacterial antibiotic resistance: the most critical pathogens. Pathogens. 10(10), 13-10.
37. Mba I.E., Nweze E.I.,2021. Nanoparticles as therapeutic options for treating multidrug-resistant bacteria: research progress, challenges, and prospects. World Journal of Microbiology and Biotechnology. 37, 1-30.
38. Hommes J.W., Surewaard B.G., 2022. Intracellular habitation of Staphylococcus aureus: molecular mechanisms and prospects for antimicrobial therapy. Biomedicines. 10(8), 1804.
39. Surewaard B.G., Deniset J.F., Zemp F.J., Amrein M., Otto M.,Conly J., Kubes P., 2016. Identification and treatment of the Staphylococcus aureus reservoir in vivo. Journal of Experimental Medicine. 213(7), 1141-1151.
40. Kang K., Jung H., Seok Lim J ,2012. Cell death by polyvinylpyrrolidine-coated silver nanoparticles is mediated by ROS-dependent signaling. Biomolecules & therapeutics. 20(4), 399.
41. Krętowski R., Kusaczuk M., Naumowicz M., Kotyńska J., Szynaka B., 2017. The effects of silica nanoparticles on apoptosis and autophagy of glioblastoma cell lines. Nanomaterials. 7(8), 230.
42. Freese C., Anspach L., Deller R.C., Richards S.J., Unger R.E., 2017. Gold nanoparticle interactions with endothelial cells cultured under physiological conditions. Biomaterials Science. 5(4), 707-717.