Generic placeholder image

Current Nanomedicine


ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Research Article

Therapeutic Effect of Chitosan-Zinc Oxide Nanoparticles on Acute Kidney Injury Induced by Gentamicin in Wistar Rats

Author(s): Dalia Yousry Saad, Hadeer Adel Khalil, Asmaa E. Farouk, Amel M. Soliman and Ayman Saber Mohamed*

Volume 13, Issue 3, 2023

Published on: 22 August, 2023

Page: [217 - 227] Pages: 11

DOI: 10.2174/2468187313666230821153922

Price: $65


Background: Gentamicin (GM) is an antibiotic frequently used to treat severe gramnegative infections. However, due to nephrotoxicity, its clinical application is restricted. Several lines of evidence indicate that free radicals are important mediators of gentamicin nephrotoxicity. Therefore, the purpose of this research was to examine the potential antioxidant therapeutic value of ZnO-chitosan nanoparticles on gentamicin-induced nephrotoxicity.

Methods: Twenty-four rats were divided into four groups (6 rats/group). All groups except group 1 were injected with gentamicin (100 mg/kg body weight i.p.) for eight days. On day 9, rats of groups 1 and 2 were administrated distilled water, and those of groups 3 and 4 were administrated 1/10 and 1/20 LD50 of ZnO-CS-NPs continuously for 30 days.

Results: Treatment with ZnO-CS NPs caused a significant decrease in urea, creatinine, uric acid, sodium, potassium, chloride, microalbumin, and malondialdehyde levels; this was accompanied by a significant increase in kidney glutathione reduced, nitric oxide, superoxide dismutase, glutathione S-transferase, and catalase.

Conclusion: The findings of the current study revealed that ZnO-CS NP ameliorated kidney injury against gentamicin induced-acute kidney injury in rats by its antioxidant properties.

Keywords: Gentamicin, zinc oxide, chitosan, nephrotoxicity, nanoparticles, FTIR spectroscopy

Graphical Abstract
Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers 2021; 7(1): 52.
[] [PMID: 34267223]
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012; 120(4): c179-84.
[] [PMID: 22890468]
Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet 2019; 394(10212): 1949-64.
[] [PMID: 31777389]
Childs-Kean LM, Shaeer KM, Varghese Gupta S, Cho JC. Aminoglycoside allergic reactions. Pharmacy 2019; 7(3): 124.
[] [PMID: 31470509]
Jospe-Kaufman M, Siomin L, Fridman M. The relationship between the structure and toxicity of aminoglycoside antibiotics. Bioorg Med Chem Lett 2020; 30(13): 127218.
[] [PMID: 32360102]
Beganovic M, Luther MK, Rice LB, Arias CA, Rybak MJ, LaPlante KL. A review of combination antimicrobial therapy for enterococcus faecalis bloodstream infections and infective endocarditis. Clin Infect Dis 2018; 67(2): 303-9.
[] [PMID: 29390132]
Al-Azzam SI, Abdul-Razzak KK, Jaradat MW. The nephroprotective effects of pioglitazone and glibenclamide against gentamicin-induced nephrotoxicity in rats: A comparative study. J Chemother 2010; 22(2): 88-91.
[] [PMID: 20435566]
Nasrollahzadeh M, Sajadi SM, Sajjadi M, Issaabadi Z. An introduction to nanotechnology. In: Nasrollahzadeh M, Sajadi SM, Sajjadi M, Issaabadi Z, Atarod M, Eds. Interface Science and Technology. Elsevier 2019; pp. 1-27.
Meng Q, Sun Y, Cong H, Hu H, Xu FJ. An overview of chitosan and its application in infectious diseases. Drug Deliv Transl Res 2021; 11(4): 1340-51.
[] [PMID: 33496926]
Ahsan SM, Thomas M, Reddy KK, Sooraparaju SG, Asthana A, Bhatnagar I. Chitosan as biomaterial in drug delivery and tissue engineering. Int J Biol Macromol 2018; 110: 97-109.
[] [PMID: 28866015]
Tamer T. aacute K, Mohyeldin M, Soltes L. Free radical scavenger activity of chitosan and its aminated derivative. J Appl Pharm Sci 2016; 6(4): 195-201.
Sarangapani S, Patil A, Ngeow YK, Elsa Mohan R, Asundi A, Lang MJ. Chitosan nanoparticles’ functionality as redox active drugs through cytotoxicity, radical scavenging and cellular behaviour. Integr Biol 2018; 10(5): 313-24.
[] [PMID: 29721564]
Muthu M, Gopal J, Chun S, Devadoss AJP, Hasan N, Sivanesan I. Crustacean waste-derived chitosan: Antioxidant properties and future perspective. Antioxidants 2021; 10(2): 228.
[] [PMID: 33546282]
Divya K, Jisha MS. Chitosan nanoparticles preparation and applications. Environ Chem Lett 2018; 16(1): 101-12.
Czyżowska A, Barbasz A. A review: Zinc oxide nanoparticles - friends or enemies? Int J Environ Health Res 2022; 32(4): 885-901.
[] [PMID: 32772735]
Chandrasekaran S, Anusuya S, Anbazhagan V. Anticancer, anti-diabetic, antimicrobial activity of zinc oxide nanoparticles: A comparative analysis. J Mol Struct 2022; 1263: 133139.
Batool M, Khurshid S, Qureshi Z, Daoush WM. Adsorption, antimicrobial and wound healing activities of biosynthesised zinc oxide nanoparticles. Chem Pap 2021; 75(3): 893-907.
Singh TA, Sharma A, Tejwan N, Ghosh N, Das J, Sil PC. A state of the art review on the synthesis, antibacterial, antioxidant, antidiabetic and tissue regeneration activities of zinc oxide nanoparticles. Adv Colloid Interface Sci 2021; 295: 102495.
[] [PMID: 34375877]
Jiang J, Pi J, Cai J. The advancing of zinc oxide nanoparticles for biomedical applications. Bioinorg Chem Appl 2018; 2018: 1062562.
Alahdal FAM, Qashqoosh MTA, Manea YK, Salem MAS, Khan AMT, Naqvi S. Eco-friendly synthesis of zinc oxide nanoparticles as nanosensor, nanocatalyst and antioxidant agent using leaf extract of P. Austroarabica. OpenNano 2022; 8: 100067.
Hübner C, Haase H. Interactions of zinc- and redox-signaling pathways. Redox Biol 2021; 41: 101916.
[] [PMID: 33662875]
Li Y, Zhang H. A novel, kinetically stable copper, zinc superoxide dismutase from Psychropotes longicauda. Int J Biol Macromol 2019; 140: 998-1005.
[] [PMID: 31408658]
Hafez A, Nassef E, Fahmy M, Elsabagh M, Bakr A, Hegazi E. Impact of dietary nano-zinc oxide on immune response and antioxidant defense of broiler chickens. Environ Sci Pollut Res Int 2020; 27(16): 19108-14.
[] [PMID: 30715696]
AbdElhady M M. Preparation and characterization of chitosan/zinc oxide nanoparticles for imparting antimicrobial and UV protection to cotton fabric. Int J Carbohydr Chem 2012; 2012: 6.
Chinedu E, Arome D, Ameh F. A new method for determining acute toxicity in animal models. Toxicol Int 2013; 20(3): 224-6.
[] [PMID: 24403732]
Brkić BM, Rovčanin B, Stojanović M, Srebro D, Vučković S, Savić Vujović K. Chloroquine attenuates oxidative stress in gentamicin-induced nephrotoxicity in rats. Dose Response 2022; 20(3)
[] [PMID: 36003319]
Bancrof J, Stevens A. Theory and Practice of Histological Techniques New York. NY, USA: Churchill Levingstone 1996.
James MT, Bhatt M, Pannu N, Tonelli M. Long-term outcomes of acute kidney injury and strategies for improved care. Nat Rev Nephrol 2020; 16(4): 193-205.
[] [PMID: 32051567]
Zhao D, Yu S, Sun B, Gao S, Guo S, Zhao K. Biomedical applications of chitosan and its derivative nanoparticles. Polymers 2018; 10(4): 462.
[] [PMID: 30966497]
Sharifi-Rad J, Quispe C, Butnariu M, et al. Chitosan nanoparticles as a promising tool in nanomedicine with particular emphasis on oncological treatment. Cancer Cell Int 2021; 21(1): 318.
[] [PMID: 34167552]
Li Y, Zhou Y, Wang Z, Cai R, Yue T, Cui L. Preparation and characterization of chitosan–Nano-ZnO composite films for preservation of cherry tomatoes. Foods 2021; 10(12): 3135.
[] [PMID: 34945686]
Kalaivani R, Maruthupandy M, Muneeswaran T, et al. Synthesis of chitosan mediated silver nanoparticles (Ag NPs) for potential antimicrobial applications. Front Lab Med 2018; 2(1): 30-5.
Katas H, Moden NZ, Lim CS, et al. Biosynthesis and potential applications of silver and gold nanoparticles and their chitosan-based nanocomposites in nanomedicine. J Nanotechnol 2018; 2018: 1-13.
Ali BH, Al-Qarawi AA, Haroun EM, Mousa HM. The effect of treatment with gum Arabic on gentamicin nephrotoxicity in rats: A preliminary study. Ren Fail 2003; 25(1): 15-20.
[] [PMID: 12617329]
Ali BH, Gayoum AAA, Bashir AA. Gentamicin nephrotoxicity in rat: Some biochemical correlates. Pharmacol Toxicol 1992; 70(6): 419-23.
[] [PMID: 1438019]
Erdem A, Gündogan NÜ, Usubütün A, et al. The protective effect of taurine against gentamicin‐induced acute tubular necrosis in rats. Nephrol Dial Transplant 2000; 15(8): 1175-82.
[] [PMID: 10910441]
Abdelrahman RS. Protective effect of apocynin against gentamicin-induced nephrotoxicity in rats. Hum Exp Toxicol 2018; 37(1): 27-37.
[] [PMID: 28116922]
Griffin BR, Faubel S, Edelstein CL. Biomarkers of drug-induced kidney toxicity. Ther Drug Monit 2019; 41(2): 213-26.
[] [PMID: 30883514]
Kwiatkowska E. Domański L, Dziedziejko V, Kajdy A, Stefańska K, Kwiatkowski S. The mechanism of drug nephrotoxicity and the methods for preventing kidney damage. Int J Mol Sci 2021; 22(11): 6109.
[] [PMID: 34204029]
Nakada T, Kudo T, Kume T, Kusuhara H, Ito K. Estimation of changes in serum creatinine and creatinine clearance caused by renal transporter inhibition in healthy subjects. Drug Metab Pharmacokinet 2019; 34(4): 233-8.
[] [PMID: 31176593]
Mishra OP, Prasad R. Microalbuminuria and serum cystatin C: Bioity. markers for early detection of kidney injury in children with obes. Indian J Pediatr 2020; 87(12): 991-2.
[] [PMID: 33047256]
Prasad RM, Tikaria R. Microalbuminuria. Treasure Island, FL: StatPearls Publishing 2022.
Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J 2017; 16: 388-99.
[PMID: 28507482]
Assmus AM, Mullins JJ, Brown CM, Mullins LJ. Cellular plasticity: A mechanism for homeostasis in the kidney. Acta Physiol 2020; 229(1): e13447.
[] [PMID: 31991057]
Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS. Oxidant mechanisms in renal injury and disease. Antioxid Redox Signal 2016; 25(3): 119-46.
[] [PMID: 26906267]
Pisoschi AM, Pop A, Iordache F, Stanca L, Predoi G, Serban AI. Oxidative stress mitigation by antioxidants - An overview on their chemistry and influences on health status. Eur J Med Chem 2021; 209: 112891.
[] [PMID: 33032084]
Uddin MS, Al Mamun A, Kabir MT, et al. Neuroprotective role of polyphenols against oxidative stress-mediated neurodegeneration. Eur J Pharmacol 2020; 886: 173412.
[] [PMID: 32771668]
Tomsa AM, Alexa AL, Junie ML, Rachisan AL, Ciumarnean L. Oxidative stress as a potential target in acute kidney injury. PeerJ 2019; 7: e8046.
[] [PMID: 31741796]
Jado JC, Humanes B, González-Nicolás MÁ, et al. Nephroprotective effect of cilastatin against gentamicin-induced renal injury in vitro and in vivo without altering its bactericidal efficiency. Antioxidants 2020; 9(9): 821.
[] [PMID: 32899204]
Ungur RA, Borda IM, Codea RA, et al. A flavonoid-rich extract of sambucus nigra L. Reduced lipid peroxidation in a rat experimental model of gentamicin nephrotoxicity. Materials 2022; 15(3): 772.
[] [PMID: 35160718]
Su LJ, Zhang JH, Gomez H, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev 2019; 2019: 1-13.
[] [PMID: 31737171]
Veljovic T, Djuric M, Mirnic J, et al. Lipid peroxidation levels in saliva and plasma of patients suffering from periodontitis. J Clin Med 2022; 11(13): 3617.
[] [PMID: 35806902]
Ahmad A, Dempsey S, Daneva Z, et al. Role of nitric oxide in the cardiovascular and renal systems. Int J Mol Sci 2018; 19(9): 2605.
[] [PMID: 30177600]
Lee J, Bae EH, Ma SK, Kim SW. Altered nitric oxide system in cardiovascular and renal diseases. CMJ 2016; 52(2): 81-90.
Hsu CN, Tain YL. Regulation of nitric oxide production in the developmental programming of hypertension and kidney disease. Int J Mol Sci 2019; 20(3): 681.
[] [PMID: 30764498]
Radi R. Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proc Natl Acad Sci USA 2018; 115(23): 5839-48.
[] [PMID: 29802228]
Valgimigli L, Baschieri A, Amorati R. Antioxidant activity of nanomaterials. J Mater Chem B Mater Biol Med 2018; 6(14): 2036-51.
[] [PMID: 32254427]
Javed R, Rais F, Fatima H, et al. Chitosan encapsulated ZnO nanocomposites: Fabrication, characterization, and functionalization of bio-dental approaches. Mater Sci Eng C 2020; 116: 111184.
[] [PMID: 32806262]
Toz H. Değer Y. The effect of chitosan on the erythrocyte antioxidant potential of lead toxicity-induced rats. Biol Trace Elem Res 2018; 184(1): 114-8.
[] [PMID: 28971372]
Barakat LAA, Barakat N, Zakaria MM, Khirallah SM. Protective role of zinc oxide nanoparticles in kidney injury induced by cisplatin in rats. Life Sci 2020; 262: 118503.
[] [PMID: 33007311]
Abd El-Khalik SR, Nasif E, Arakeep HM, Rabah H, Rabah H. The prospective ameliorative role of zinc oxide nanoparticles in STZ-induced diabetic nephropathy in rats: Mechanistic targeting of autophagy and regulating Nrf2/TXNIP/NLRP3 inflammasome signaling. Biol Trace Elem Res 2022; 200(4): 1677-87.
[] [PMID: 34241775]
Ahmed F, Husain Q, Ansari MO, Shadab GGHA. Antidiabetic and oxidative stress assessment of bio-enzymatically synthesized zinc oxide nanoformulation on streptozotocin-induced hyperglycemic mice. Appl Nanosci 2020; 10(3): 879-93.
Muthuraman P, Ramkumar K, Kim DH. Analysis of dose-dependent effect of zinc oxide nanoparticles on the oxidative stress and antioxidant enzyme activity in adipocytes. Appl Biochem Biotechnol 2014; 174(8): 2851-63.
[] [PMID: 25234395]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy