Effect of the Antioxidant Pharmacological Agent Mexidol on Locomotor Behavior in Rats Impaired by Silver Nanoparticles

Karpukhina OV; Inozemtsev AN; Kalinina IG

Karpukhina OV, Inozemtsev AN and Kalinina IG

Volume6-Issue11
Dates: Received: 2025-11-10 | Accepted: 2025-11-25 | Published: 2025-11-26
Pages: 1715-1722

Abstract

Nanosilver (AgNPs) is widely used in various manufacturing sectors, including agriculture, food processing, and medicine. Many consumer products used in everyday life release silver either as ions or nanoparticles. Without proper regulation, consumption of Ag-containing materials will lead to significant risks for ecosystems and humans. Nonspecific oxidative stress is considered one of the most serious problems associated with nanoparticle toxicity. In this regard, research into the use of antioxidant drugs to prevent and protect against the negative consequences caused by exposure to Ag NPs on the body is promising. The purpose of this work was to evaluate the effect of the antioxidant drug Mexidol on the motor behaviour of rats that received daily Ag NPS with drinking water. For two weeks, rats in the 1 experimental group received an aqueous solution with 10-12 nm particles added to their drinking water. The daily dose of Ag NPs was 15.75 mg/kg. The second group of rats additionally received Mexidol, an antioxidant drug, intraperitoneally at a dose of 10 mg/kg as a 0.5% solution twice daily. All animals were tested in an Open Field (OF) on the first and 15th day of the experiment. During the final testing in the OF, urine samples were collected from the rats using dry chemistry test strips. Rats receiving Ag NPs in their drinking water for two weeks urine analysis revealed significant impairment of renal function. Chronic exposure to Ag NPs can negatively impact fundamental behavioural patterns in rats, particularly their stress responses and locomotor activity. In 1 group of rats defined a decrease in locomotor activity and an increase in anxiety-like behaviour compared to the first day of the experiment. In rats additionally receiving Mexidol injections, the drug improved exploratory behaviour and reduced emotional responses

FullText HTML FullText PDF DOI: 10.37871/jbres2224

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How to cite this article

Karpukhina OV, Inozemtsev AN, Kalinina IG. Effect of the Antioxidant Pharmacological Agent Mexidol on Locomotor Behavior in Rats Impaired by Silver Nanoparticles. J Biomed Res Environ Sci. 2025 Nov 26; 6(11): 1715-1722. doi: 10.37871/jbres2224, Article ID: JBRES2224, Available at: https://www.jelsciences.com/ articles/jbres2224.pdf

Subject area(s)

Biomedicine

Biochemistry

Toxicology

References

Nowack B, Krug HF, Height M. 120 years of nanosilver history: implications for policy makers. Environ Sci Technol. 2011 Feb 15;45(4):1177-83. doi: 10.1021/es103316q. Epub 2011 Jan 10. Erratum in: Environ Sci Technol. 2011 Apr 1;45(7):3189. PMID: 21218770.
Medici S, Peana M, Nurchi VM, Zoroddu MA. Medical Uses of Silver: History, Myths, and Scientific Evidence. J Med Chem. 2019 Jul 11;62(13):5923-5943. doi: 10.1021/acs.jmedchem.8b01439. Epub 2019 Feb 21. PMID: 30735392.
Ferdous Z, Nemmar A. Health Impact of Silver Nanoparticles: A Review of the Biodistribution and Toxicity Following Various Routes of Exposure. Int J Mol Sci. 2020 Mar 30;21(7):2375. doi: 10.3390/ijms21072375. PMID: 32235542; PMCID: PMC7177798.
Stanishevskaya IE, Stoinova AM, Marakhova AI, Stanishevskiy YM. Silver nanoparticles: Preparation and use for medical purposes. Drug Development and Registration. 2016;(1):66-69.
Rezvani E, Rafferty A, McGuinness C, Kennedy J. Adverse effects of nanosilver on human health and the environment. Acta Biomater. 2019 Aug;94:145-159. doi: 10.1016/j.actbio.2019.05.042. Epub 2019 May 22. PMID: 31125729.
Gaillet S, Rouanet JM. Silver nanoparticles: their potential toxic effects after oral exposure and underlying mechanisms--a review. Food Chem Toxicol. 2015 Mar;77:58-63. doi: 10.1016/j.fct.2014.12.019. Epub 2014 Dec 30. PMID: 25556118.
Bamal D, Singh A, Chaudhary G, Kumar M, Singh M, Rani N, Mundlia P, Sehrawat AR. Silver Nanoparticles Biosynthesis, Characterization, Antimicrobial Activities, Applications, Cytotoxicity and Safety Issues: An Updated Review. Nanomaterials (Basel). 2021 Aug 17;11(8):2086. doi: 10.3390/nano11082086. PMID: 34443916; PMCID: PMC8402060.
Khanna P, Ong C, Bay BH, Baeg GH. Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death. Nanomaterials (Basel). 2015 Jun 30;5(3):1163-1180. doi: 10.3390/nano5031163. PMID: 28347058; PMCID: PMC5304638.
Horie M, Tabei Y. Role of oxidative stress in nanoparticles toxicity. Free Radic Res. 2021 Apr;55(4):331-342. doi: 10.1080/10715762.2020.1859108. Epub 2020 Dec 18. PMID: 33336617.
Cameron SJ, Hosseinian F, Willmore WG. A Current Overview of the Biological and Cellular Effects of Nanosilver. Int J Mol Sci. 2018 Jul 12;19(7):2030. doi: 10.3390/ijms19072030. PMID: 30002330; PMCID: PMC6073671.
Jaswal T, Gupta J. A review on the toxicity of silver nanoparticles on human health. Materials Today Proceedings. 2023;81:859-863. doi: 10.1016/j.matpr.2021.04.266.
Suthar JK, Vaidya A, Ravindran S. Toxic implications of silver nanoparticles on the central nervous system: A systematic literature review. J Appl Toxicol. 2023 Jan;43(1):4-21. doi: 10.1002/jat.4317. Epub 2022 Mar 23. PMID: 35285037.
Patlolla AK, Hackett D, Tchounwou PB. Silver nanoparticle-induced oxidative stress-dependent toxicity in Sprague-Dawley rats. Mol Cell Biochem. 2015 Jan;399(1-2):257-68. doi: 10.1007/s11010-014-2252-7. Epub 2014 Oct 30. PMID: 25355157; PMCID: PMC4268425.
Flores-López LZ, Espinoza-Gómez H, Somanathan R. Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative stress, beneficial and toxicological effects. Mini review. J Appl Toxicol. 2019 Jan;39(1):16-26. doi: 10.1002/jat.3654. Epub 2018 Jun 25. PMID: 29943411.
Halliwell B. How to characterize a biological antioxidant. Free Radic Res Commun. 1990;9(1):1-32. doi: 10.3109/10715769009148569. PMID: 2159941.
Voronina TA. Pioneer of antioxidant neuroprotection 20 years in clinical practice. Russian Medical Journal Neurology. 2016;7:434-438.
Sambale F, Wagner S, Stahl F, Khaydarov RR, Scheper T, Bahnemann D. Investigations of the toxic effect of silver nanoparticles on mammalian cell lines. Journal of Nanomaterials. 2015;1:136765. doi: 10.1155/2015/136765.
Vazquez-Muñoz R, Borrego B, Juárez-Moreno K, García-García M, Mota Morales JD, Bogdanchikova N, Huerta-Saquero A. Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter? Toxicol Lett. 2017 Jul 5;276:11-20. doi: 10.1016/j.toxlet.2017.05.007. Epub 2017 May 5. PMID: 28483428.
Ryan J, Jacob P, Lee A, Gagnon Z, Pavel IE. Biodistribution and toxicity of antimicrobial ionic silver (Ag+) and silver nanoparticle (AgNP+) species after oral exposure, in Sprague-Dawley rats. Food Chem Toxicol. 2022 Aug;166:113228. doi: 10.1016/j.fct.2022.113228. Epub 2022 Jun 13. PMID: 35710031.
Kreyling WG, Holzwarth U, Hirn S, Schleh C, Wenk A, Schäffler M, Haberl N, Gibson N. Quantitative biokinetics over a 28 day period of freshly generated, pristine, 20 nm silver nanoparticle aerosols in healthy adult rats after a single 1½-hour inhalation exposure. Part Fibre Toxicol. 2020 Jun 5;17(1):21. doi: 10.1186/s12989-020-00347-1. PMID: 32503677; PMCID: PMC7275317.
Benn T, Cavanagh B, Hristovski K, Posner JD, Westerhoff P. The release of nanosilver from consumer products used in the home. J Environ Qual. 2010 Nov-Dec;39(6):1875-82. doi: 10.2134/jeq2009.0363. PMID: 21284285; PMCID: PMC4773917.
Nosrati H, Hamzepoor M, Sohrabi M, Saidijam M, Assari MJ, Shabab N, Gholami Mahmoudian Z, Alizadeh Z. The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms. BMC Nephrol. 2021 Jun 18;22(1):228. doi: 10.1186/s12882-021-02428-5. PMID: 34144690; PMCID: PMC8212496.
Qi M, Wang X, Chen J, Liu Y, Liu Y, Jia J, Li L, Yue T, Gao L, Yan B, Zhao B, Xu M. Transformation, Absorption and Toxicological Mechanisms of Silver Nanoparticles in the Gastrointestinal Tract Following Oral Exposure. ACS Nano. 2023 May 23;17(10):8851-8865. doi: 10.1021/acsnano.3c00024. Epub 2023 May 5. PMID: 37145866.
Jayati B, Lorraine B, Cotton P, Harding J, Holmes T, Ljumanovic N, McClure F, McGuire A, McInnes L, Prior H, Sewell F. Applying the 3Rs to urinalysis assessments in toxicity studies: Refining procedures and adopting a case-by-case approach. Comp Clin Pathol. 2025;34:311-322. doi: 10.1007/s00580-025-03642-5.
Lentini P, Zanoli L, Granata A, Signorelli SS, Castellino P, Dell'Aquila R. Kidney and heavy metals - The role of environmental exposure (Review). Mol Med Rep. 2017 May;15(5):3413-3419. doi: 10.3892/mmr.2017.6389. Epub 2017 Mar 24. PMID: 28339049.
Pócsi I, Dockrell ME, Price RG. Nephrotoxic Biomarkers with Specific Indications for Metallic Pollutants: Implications for Environmental Health. Biomark Insights. 2022 Jul 14;17:11772719221111882. doi: 10.1177/11772719221111882. PMID: 35859925; PMCID: PMC9290154.
Kirsanova AYU, Kubrak NV. Urine sediment parameters in healthy wistar rats. Laboratory Animals for Scientific Research. 2022;1:3-7. doi: 10.29296/2618723X-2022-01-01.
Ryabova YV, Minigalieva IA, Sutunkova MP, Klinova SV, Tsaplina AK, Valamina IE, Petrunina EM, Tsatsakis AM, Mamoulakis C, Stylianou K, Kuzmin SV, Privalova LI, Katsnelson BA. Toxic Kidney Damage in Rats Following Subchronic Intraperitoneal Exposure to Element Oxide Nanoparticles. Toxics. 2023 Sep 19;11(9):791. doi: 10.3390/toxics11090791. PMID: 37755801; PMCID: PMC10537166.
Tucker PS, Scanlan AT, Dalbo VJ. Chronic kidney disease influences multiple systems: describing the relationship between oxidative stress, inflammation, kidney damage, and concomitant disease. Oxid Med Cell Longev. 2015;2015:806358. doi: 10.1155/2015/806358. Epub 2015 Mar 15. PMID: 25861414; PMCID: PMC4377508.
Watanabe K, Watanabe T, Nakayama M. Cerebro-renal interactions: impact of uremic toxins on cognitive function. Neurotoxicology. 2014 Sep;44:184-93. doi: 10.1016/j.neuro.2014.06.014. Epub 2014 Jul 6. PMID: 25003961.
Fujisaki K, Tsuruya K, Yamato M, Toyonaga J, Noguchi H, Nakano T, Taniguchi M, Tokumoto M, Hirakata H, Kitazono T. Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: neuroprotective effect of tempol. Nephrol Dial Transplant. 2014 Mar;29(3):529-38. doi: 10.1093/ndt/gft327. Epub 2013 Sep 12. PMID: 24030834.
Sinyuhin VN, Rabinovich EZ, Sokolov MA, Sivkov AV. Neurological disorders in patients with chronic kidney disease. Experimental and Clinical Urology. 2017;2:92-101.
Yang Y, Wang JZ. From Structure to Behavior in Basolateral Amygdala-Hippocampus Circuits. Front Neural Circuits. 2017 Oct 31;11:86. doi: 10.3389/fncir.2017.00086. PMID: 29163066; PMCID: PMC5671506.
Antsiferova A, Kopaeva M, Kashkarov P. Effects of Prolonged Silver Nanoparticle Exposure on the Contextual Cognition and Behavior of Mammals. Materials (Basel). 2018 Apr 5;11(4):558. doi: 10.3390/ma11040558. PMID: 29621146; PMCID: PMC5951442.
Węsierska M, Dziendzikowska K, Gromadzka-Ostrowska J, Dudek J, Polkowska-Motrenko H, Audinot JN, Gutleb AC, Lankoff A, Kruszewski M. Silver ions are responsible for memory impairment induced by oral administration of silver nanoparticles. Toxicol Lett. 2018 Jun 15;290:133-144. doi: 10.1016/j.toxlet.2018.03.019. Epub 2018 Mar 22. PMID: 29578054.