تاثير نانوذرات Ag، Cu و ZnO بر بيان TNF-α در موشهای Balb/C آلوده به استافيلوكوكوس اورئوس
محورهای موضوعی : میکروب شناسی مولکولی
یگانه غلامی
1
,
بهناز اسفندیاری
2
*
,
جواد آراسته
3
1 - گروه زیست شناسی، واحد تهران مرکزی، دانشگاه آزاد اسلامی، تهران، ایران.
2 - گروه زیست شناسی، واحد اسلامشهر، دانشگاه آزاد اسلامی، اسلامشهر، ایران.
3 - دانشکده علوم پایه، گروه زیست شناسی، دانشگاه آزاد اسلامی، واحد تهران مرکزی.
کلید واژه: استافیلوکوکوس اورئوس, MRSA, TNF-α, نانوذرات, MIC, MBC.,
چکیده مقاله :
سابقه و هدف: مقاومت به آنتیبیوتیکها، بهویژه در استافیلوکوکوس اورئوس مقاوم به متیسیلین (MRSA)، یک چالش جهانی است. نانوذرات (NPs) مانند نقره (Ag)، مس (Cu) و اکسید روی (ZnO) پتانسیل ضدباکتریایی دارند. این مطالعه اثربخشی این نانوذرات را علیه MRSA و تأثیرشان بر بیان ژن TNF-α در موشهای Balb/c بررسی کرد.
مواد و روشها: ۶۳ موش به ۹ گروه (۷تایی) تقسیم شدند. گروههای ۵ تا ۹ با MRSA آلوده و سپس با نانوذرات Ag (15.625 mg/L) ، Cu (62.5 mg/L)، Zno وانکومایسین یا محلول نمکی درمان شدند. پس از ۱ و ۵ روز، بیان TNF-α در طحال با Real-Time PCR سنجش شد. همچنین MIC و MBC نانوذرات تعیین گردید.
یافتهها: نانوذرات Ag و Cu اثرات بازدارندگی و باکتریکشی داشتند، درحالیکه ZnO بیاثر بود. در روز ۵، بیان TNF-α در گروه وانکومایسین بهطور معنیداری افزایش یافت و پس از آن نانوذرات Ag، Cu و ZnO بیشترین اثر را نشان دادند. در روز ۱، تنها وانکومایسین، Ag و Cu بیان TNF-α را افزایش دادند.
نتیجهگیری: نانوذرات Ag بیشترین تأثیر را بر بیان TNF-α داشتند، که نشاندهنده پتانسیل ضدباکتریایی برتر آنهاست. این نتایج از کاربرد نانوذرات بهعنوان جایگزین یا مکمل آنتیبیوتیکها در عفونتهای MRSA حمایت میکند.
Background and Objective: Antibiotic resistance, especially in methicillin-resistant Staphylococcus aureus (MRSA), is a global challenge. Nanoparticles (NPs) such as silver (Ag), copper (Cu), and zinc oxide (ZnO) have shown antibacterial potential. This study aimed to evaluate the effectiveness of these nanoparticles against MRSA and their impact on TNF-α gene expression in Balb/c mice.
Materials and Methods: Sixty-three mice were divided into nine groups of seven. Groups 5 to 9 were infected with MRSA and then treated with Ag (15.625 mg/L), Cu (62.5 mg/L), ZnO nanoparticles, vancomycin, or saline solution. TNF-α expression in the spleen was measured by Real-Time PCR on days 1 and 5. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the nanoparticles were also determined.
Results: Ag and Cu nanoparticles showed inhibitory and bactericidal effects, while ZnO was ineffective. On day 5, TNF-α expression significantly increased in the vancomycin group, followed by Ag, Cu, and ZnO groups. On day 1, only vancomycin, Ag, and Cu nanoparticles increased TNF-α expression.
Conclusion: These findings indicate that Ag NPs, through modulation of TNF-α expression in Balb/c mice, may serve as promising antibacterial agents warranting further translational studies.
1. Rahmati F, Hosseini SS, Mahuti Safai S, Asgari Lajayer B, Hatami M. New insights into the role of nanotechnology in microbial food safety. 3 Biotech. 2020;10(10):1–15.
2. Shalaby M-AW, Dokla EM, Serya RA, Abouzid KA. Penicillin binding protein 2a: An overview and a medicinal chemistry perspective. European Journal of Medicinal Chemistry. 2020;199:112312.
3. Rahmati F. Characterization of Lactobacillus, Bacillus and Saccharomyces isolated from Iranian traditional dairy products for potential sources of starter cultures. AIMS microbiology. 2017;3(4):815.
4. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. Pharmacy and therapeutics. 2015;40(4):277.
5. Das S, Chakraborty J, Chatterjee S, Kumar H. Prospects of biosynthesized nanomaterials for the remediation of organic and inorganic environmental contaminants. Environmental Science: Nano. 2018;5(12):2784–808.
6. Khorsandi K, Hosseinzadeh R, Sadat Esfahani H, Keyvani-Ghamsari S, Ur Rahman S. Nanomaterials as drug delivery systems with antibacterial properties: Current trends and future priorities. Expert Review of Anti-infective Therapy. 2021;19(10):1299–323.
7. Li P, Li J, Wu C, Wu Q, Li J. Synergistic antibacterial effects ofβ-lactam antibiotic combined with silver nanoparticles. Nanotechnology. 2005;16(9):1912.
8. Cheng C, Qin Y, Shao X, Wang H, Gao Y, Cheng M, et al. Induction of TNF-α by LPS in Schwann cell is regulated by MAPK activation signals. Cellular and molecular neurobiology. 2007;27(7):909–21.
9. Ha MK, Kwon SJ, Choi JS, Nguyen NT, Song J, Lee Y, et al. Mass Cytometry and Single‐Cell RNA‐seq Profiling of the Heterogeneity in Human Peripheral Blood Mononuclear Cells Interacting with Silver Nanoparticles. Small. 2020;16(21):1907674.
10. Shin S-H, Ye M-K, Kim H-S, Kang H-S. The effects of nano-silver on the proliferation and cytokine expression by peripheral blood mononuclear cells. International immunopharmacology. 2007;7(13):1813–8.
11. Foldbjerg R, Dang DA, Autrup H. Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Archives of toxicology. 2011;85:743–50.
12. Raza MA, Kanwal Z, Rauf A, Sabri AN, Riaz S, Naseem S. Size-and shape-dependent antibacterial studies of silver nanoparticles synthesized by wet chemical routes. Nanomaterials. 2016;6(4):74.
13. Omidi A, Sharifi A. The effect of methanolic extracts of plants Quercus brantii, Pistacia atlantica and Elaeagnus angustifolia on Biofilm formation of Pseudomonas aeruginosa. 2017.
14. Mahon CR, Manuselis G. Textbook of diagnostic microbiology: WB Saunders company; 2000.
15. Wiegand I, Hilpert K, Hancock RE. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nature protocols. 2008;3(2):163–75.
16. Andrews JM. Determination of minimum inhibitory concentrations. Journal of antimicrobial Chemotherapy. 2001;48(suppl_1):5–16.
17. Abdelghafar A, Yousef N, Askoura M. Zinc oxide nanoparticles reduce biofilm formation, synergize antibiotics action and attenuate Staphylococcus aureus virulence in host; an important message to clinicians. BMC microbiology. 2022;22(1):244.
18. Levin-Arama M, Abraham L, Waner T, Harmelin A, Steinberg DM, Lahav T, et al. Subcutaneous compared with intraperitoneal ketamine–xylazine for anesthesia of mice. Journal of the American Association for Laboratory Animal Science. 2016;55(6):794–800.
19. Maan S, et al. Rapid cDNA synthesis and sequencing techniques for the genetic study of bluetongue and other dsRNA viruses. Journal of virological methods,. 2007;143.
20. Nolan T, R.E. Hands, and S.A. Bustin. Quantification of mRNA using real-time RT-PCR. Nature protocols,. 2006: 1559–82.
21. Liu Y, Imlay JA. Cell death from antibiotics without the involvement of reactive oxygen species. Science. 2013;339(6124):1210–3.
22. R HSS. Antibiotic resistance pattern of methicillin-resistant Staphylococcus aureus and the antibacterial effect of silver and copper nanoparticles in vitro and in an animal model. Journal of Microbial World. 2022;16(1):129–36.
23. Saka A, Dey SR, Jule LT, Krishnaraj R, Dhanabal R, Mishra N, et al. Investigating antibacterial activity of biosynthesized silver oxide nanoparticles using Phragmanthera Macrosolen L. leaf extract. Scientific Reports. 2024;14(1):26850.
24. Kazempour ZB, Yazdi MH, Rafii F, Shahverdi AR. Sub-inhibitory concentration of biogenic selenium nanoparticles lacks post antifungal effect for Aspergillus niger and Candida albicans and stimulates the growth of Aspergillus niger. Iranian journal of microbiology. 2013;5(1):81.
25. Rahmati F. Microencapsulation of Lactobacillus acidophilus and Lactobacillus plantarum in Eudragit S100 and alginate chitosan under gastrointestinal and normal conditions. Applied Nanoscience. 2020;10(2):391–9.
26. Cho K-H, Park J-E, Osaka T, Park S-G. The study of antimicrobial activity and preservative effects of nanosilver ingredient. Electrochimica Acta. 2005;51(5):956–60.
27. Pal S, Tak YK, Song JM. Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Applied and environmental microbiology. 2007;73(6):1712–20.
28. Dehkordi SH, Hosseinpour F, Kahrizangi AE. An in vitro evaluation of antibacterial effect of silver nanoparticles on Staphylococcus aureus isolated from bovine subclinical mastitis. African Journal of Biotechnology. 2011;10(52):10795–7.
29. Ruparelia JP, Chatterjee AK, Duttagupta SP, Mukherji S. Strain specificity in antimicrobial activity of silver and copper nanoparticles. Acta biomaterialia. 2008;4(3):707–16.
30. Gouyau J, Duval RE, Boudier A, Lamouroux E. Investigation of nanoparticle metallic core antibacterial activity: Gold and silver nanoparticles against Escherichia coli and Staphylococcus aureus. International Journal of Molecular Sciences. 2021;22(4):1905.
31. Mirhosseini M, Firouzabadi FB. Antibacterial activity of zinc oxide nanoparticle suspensions on food‐borne pathogens. International Journal of Dairy Technology. 2013;66(2):291–5.
32. Correa MG, Martínez FB, Vidal CP, Streitt C, Escrig J, de Dicastillo CL. Antimicrobial metal-based nanoparticles: a review on their synthesis, types and antimicrobial action. Beilstein journal of nanotechnology. 2020;11(1):1450–69.
33. Jiang X, Wang Y, Qin Y, He W, Benlahrech A, Zhang Q, et al. Micheliolide provides protection of mice against Staphylococcus aureus and MRSA infection by down-regulating inflammatory response. Scientific reports. 2017;7(1):1–14.
34. Vadalasetty KP, Lauridsen C, Engberg RM, Vadalasetty R, Kutwin M, Chwalibog A, et al. Influence of silver nanoparticles on growth and health of broiler chickens after infection with Campylobacter jejuni. BMC veterinary research. 2018;14(1):1–11.
35. Małaczewska J. The effect of silver nanoparticles on splenocyte activity and selected cytokine levels in the mouse serum at early stage of experimental endotoxemia. Polish Journal of Veterinary Sciences. 2011(4).