BLOOD CREATININE CONTENT AND RAT KIDNEY STRUCTURE AFTER INTRAMUSCULAR INJECTION OF PEGYLATED ANTIBIOTIC ENROFLOXACIN
DOI: http://dx.doi.org/10.30970/sbi.1703.720
Abstract
Background. Polyethylene glycol (PEG) is able to affect the permeability of membranes by increasing the entry of antibiotics into the cell of microorganism; therefore, PEGylation may improve the effectiveness of antibiotics due to chemical modification of their molecules. It is important to assess the safety and toxicity of new compounds for drug development activity. The aim of this research was to study the functional state and structure of the kidneys of laboratory rats after intramuscular administration of PEGylated antibiotic enrofloxacin, as well as commercial antibiotic enrofloxacin and polymer PEG-400, which were used for the synthesis of PEGylated antibiotic enrofloxacin.
Materials and Methods. PEGylated antibiotic enrofloxacin was obtained via the reaction between enrofloxacin chloride and PEG-400 polymer (polyethylene glycol with a molecular weight of 400 Da). The research was conducted on four groups of rats: control and three experimental ones, 12 animals in each group. Physiological saline solution was intramuscularly injected to the control rats; commercial antibiotic enrofloxacin – to rats of the first experimental group; polymer PEG-400 – to rats of the second experimental group; PEGylated antibiotic enrofloxacin – to rats of the third experimental group.
Results. The conducted studies did not show a significant difference between the serum creatinine in control rats and experimental ones on the 7th, 14th and 21st days after the last administration of the drugs. Creatinine levels in the blood of all groups of animals were within physiological ranges. Histological studies of the kidney structure in control rats indicated no changes during the experiment. Histological changes in the structure of the kidneys were observed within the first seven days after the end of the intramuscular administration of polymer PEG-400 and PEGylated antibiotic enrofloxacin. Injections of the commercial form of antibiotic enrofloxacin to experimental rats caused histological changes in the kidney structure for 21 days of the experiment.
Conclusions. Quadruple intramuscular administration of PEGylated and commercial antibiotics enrofloxacin to rats showed that PEGylation reduces nephrotoxicity and shortens the duration of adverse effects in the kidneys.
Keywords
Full Text:
PDFReferences
| Alhassani, R. Y., Bagadood, R. M., Balubaid, R. N., Barno, H. I., Alahmadi, M. O., & Ayoub, N. A. (2021). Drug therapies affecting renal function: an overview. Cureus, 13(11), e19924. doi:10.7759/cureus.19924 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Benincasa, M., Zahariev, S., Pelillo, C., Milan, A., Gennaro, R., & Scocchi, M. (2015). PEGylation of the peptide Bac7(1-35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity. European Journal of Medicinal Chemistry, 95, 210-219. doi:10.1016/j.ejmech.2015.03.028 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Bhattacharya, S., Sen, D., & Bhattacharjee, C. (2019). In vitro antibacterial effect analysis of stabilized PEGylated allicin-containing extract from Allium sativum in conjugation with other antibiotics. Process Biochemistry, 87, 221-231. doi:10.1016/j.procbio.2019.09.025 Crossref ● Google Scholar | ||||
| ||||
| Dron, I. A., Vynnytska, S. I., Oleksa, V. V., Khomyak, S. V., & Ostapiv, D. D. (2018). Synthesys and study of the antibacterial properties of pegylated enrofloxacines. Visnyk Natsionalnoho Universytetu "Lvivska Politekhnika". Serie: Khimiia, Tekhnolohiia Rechovyn ta yikh Zastosuvannia, 886, 47-51. (In Urrainian) Google Scholar | ||||
| ||||
| El-Daly, A. A. A. (2013). Histological and histochemical effects of green tea extract on enroflocsacin-induced kidnay injury in Albino rats. The Egyptian Journal of Experimental Biology (Zoology), 9(2), 237-245. Google Scholar | ||||
| ||||
| Fuchs, K., Rinder, M., Dietrich, R., Banspach, L., Ammer, H., & Korbel, R. (2022). Penetration of enrofloxacin in aqueous humour of avian eyes. Veterinary Sciences, 10(1), 5. doi:10.3390/vetsci10010005 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Gray, D. A., & Wenzel, M. (2020). Multitarget approaches against multiresistant superbugs. ACS Infectious Diseases, 6(6), 1346-1365. doi:10.1021/acsinfecdis.0c00001 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Gu, J., Clegg, J. R., Heersema, L. A., Peppas, N. A., & Smyth, H. D. C. (2020). Optimization of cationic nanogel PEGylation to achieve mammalian cytocompatibility with limited loss of Gram-negative bactericidal activity. Biomacromolecules, 21(4), 1528-1538. doi:10.1021/acs.biomac.0c00081 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Kang, J., Hossain, M. A., Park, H., Kim, Y., Lee, K., & Park, S. (2019). Pharmacokinetic and pharmacodynamic integration of enrofloxacin against Salmonella Enteritidis after administering to broiler chicken by per-oral and intravenous routes. Journal of Veterinary Science, 20(2), e15. doi:10.4142/jvs.2019.20.e15 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Klein, E. Y., Milkowska-Shibata, M., Tseng, K. K., Sharland, M., Gandra, S., Pulcini, C., & Laxminarayan, R. (2021). Assessment of WHO antibiotic consumption and access targets in 76 countries, 2000-15: an analysis of pharmaceutical sales data. The Lancet Infectious Diseases, 21(1), 107-115. doi:10.1016/s1473-3099(20)30332-7 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Lam, A. K., Moen, E. L., Pusavat, J., Wouters, C. L., Panlilio, H., Ferrell, M. J., Houck, M. B., Glatzhofer, D. T., & Rice, C. V. (2020). PEGylation of polyethylenimine lowers acute toxicity while retaining anti-biofilm and β-lactam potentiation properties against antibiotic-resistant pathogens. ACS Omega, 5(40), 26262-26270. doi:10.1021/acsomega.0c04111 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Levchenko, V. I. & Vlizlo, V. V. (Eds.). (2019). Veterynarna klinichna biokhimiia [Veterinary clinical biochemistry]. Bila Tserkva. (In Ukrainian) Google Scholar | ||||
| ||||
| Moen, E. L., Lam, A. K., Pusavat, J., Wouters, C. L., Panlilio, H., Heydarian, N., Peng, Z., Lan, Y., & Rice, C. V. (2023). Dimerization of 600 Da branched polyethylenimine improves β-lactam antibiotic potentiation against antibiotic-resistant Staphylococcus epidermidis and Pseudomonas aeruginosa. Chemical Biology & Drug Design, 101(3), 489-499. doi:10.1111/cbdd.14009 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Morales-Alvarez, M. C. (2020). Nephrotoxicity of antimicrobials and antibiotics. Advances in Chronic Kidney Disease, 27(1), 31-37. doi:10.1053/j.ackd.2019.08.001 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Mozar, F. S., & Chowdhury, E. H. (2018). Impact of PEGylated nanoparticles on tumor targeted drug delivery. Current Pharmaceutical Design, 24(28), 3283-3296. doi:10.2174/1381612824666180730161721 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Panlilio, H., Lam, A. K., Heydarian, N., Haight, T., Wouters, C. L., Moen, E. L., & Rice, C. V. (2021). Dual-function potentiation by PEG-BPEI restores activity of carbapenems and penicillins against carbapenem-resistant Enterobacteriaceae. ACS Infectious Diseases, 7(6), 1657-1665. doi:10.1021/acsinfecdis.0c00863 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Rafiq, K., Mori, H., Sherajee, S. J., Kobara, H., Nishiyama, N., & Nishiyama, A. (2016). Effects of polyethylene glycol on renal functional parameters in rats. Journal of Bangladesh Society of Physiologist, 10(2), 61-66. doi:10.3329/jbsp.v10i2.27166 Crossref ● Google Scholar | ||||
| ||||
| Soultan, A. H., Lambrechts, D., Verheyen, T., Van Gorp, H., Roeffaers, M. B. J., Smet, M., De Borggraeve, W. M., & Patterson, J. (2019). Nanocarrier systems assembled from PEGylated hyperbranched poly(arylene oxindole). European Polymer Journal, 119, 247-259. doi:10.1016/j.eurpolymj.2019.07.029 Crossref ● Google Scholar | ||||
| ||||
| Stasiuk, A., Fihurka, N., Vlizlo, V., Prychak, S., Ostapiv, D., Varvarenko, S., & Samaryk, V. (2022). Synthesis and properties of phosphorus-containing pseudo-poly(amino acid)sof polyester type based on N-derivatives of glutaminic acid. Chemistry & Chemical Technology, 16(1), 51-58. doi:10.23939/chcht16.01.051 Crossref ● Google Scholar | ||||
| ||||
| Trouchon, T., & Lefebvre, S. (2016). A review of enrofloxacin for veterinary use. Open Journal of Veterinary Medicine, 6(2), 40-58. doi:10.4236/ojvm.2016.62006 Crossref ● Google Scholar | ||||
| ||||
| Yang, S.-Y., Zhao, F.-K., Pang, H., Chen, L.-Z., Shi, R.-B., & Fang, B.-H. (2022). Pharmaceutical cocrystals and salts of enrofloxacin: structure and properties. Journal of Molecular Structure, 1265, 133335. doi:10.1016/j.molstruc.2022.133335 Crossref ● Google Scholar | ||||
| ||||
| Zelenina, O. M., Vlizlo, V. V., Ostapiv, D. D., Samaryk, V. Ja., Dron, I. A., Kozak, M. P., Kuzmina, N. V., Chernushkin, B. O., Maksymovych, I. A., Leno, M. I., Rusyn, V. I., Prystupa, O. I., Fedorovych, V. L., Lukashchuk, B. O., & Zinko, H. O. (2021). PEGylation of antibiotic enrofloxacin and its effects on the state of the antioxidant system in rats. Ukrainian Journal of Ecology, 11(1), 202-208, doi:10.15421/2020_32 Crossref ● Google Scholar | ||||
| ||||
| Zelenina, O., Vlizlo, V., Kozak, M., Ostapiv, D., Dron, I., Samaryk, V., Stetsko, T., Skrypka, M., Tomchuk, V., Danchuk, O., & Levchenko, A. (2022). Antimicrobial activity of the PEGylated antibiotic enrofloxacin and its functional and structural effect on the liver in rats. Journal of Applied Pharmaceutical Science, 68-75. doi:10.7324/japs.2022.120607 Crossref ● Google Scholar | ||||
Refbacks
- There are currently no refbacks.
Copyright (c) 2023 Mariia Kozak, Oksana Zelenina, Dmytro Ostapiv, Maryna Skrypka, Volodymyr Samaryk, Vasyl Vlizlo
This work is licensed under a Creative Commons Attribution 4.0 International License.