Transaminases activity and bilirubin level in the blood of rats after administration of the antibiotic enrofloxacin, nanopolymer PEG-400 and their complex
DOI:
https://doi.org/10.31548/dopovidi2020.04.009Keywords:
rats, antibiotic enrofloxacin, nanopolymer, AST, ALT, bilirubinAbstract
The large-scale production of antibiotics able to the targeted drug delivery to the affected tissues and target cells is relevant for ensuring an increase in the effectiveness of the humans and animals treatment. The aim of this study is to evaluate the effect of the antibiotic enrofloxacin applied alone or in combination with the nanopolymer PEG-400 on the activity of the transamination enzymes (ALT, AST) and the concentration of bilirubin in the rats’ serum. The complex enrofloxacin-PEG-400 was obtained by the reaction of enrofloxacin chloride with PEG-400. Four groups of 12 rats each were studied; there were three experimental groups and a control one. Control group rats were injected intramuscularly with saline, the first experimental group with the antibiotic enrofloxacin, the second with the nanopolymer PEG-400, the third with the complex enrofloxacin-PEG-400.
The volume of administrated drugcorresponded to the dose of enrofloxacin for animals’ treatmentand it was 0.03 ml per 200 g of rat weight for all groups. The drugs were being administered for four days, every day. Decapitation of animals was carried out in 7, 14 and 12 days after drug administration. In the blood of animals the AST / ALT activity and their ratio (de Ritis Ratio) have been studied, as well as the total bilirubin.
Seven days afterthe drugs introduction,the ALT activity in the serum of the twofirst experimental groups of rats, injected with the antibiotic enrofloxacin in its traditional form and nanopolymer PEG-400, corresponded to control values, whereas theALT activity in the blood of animals afterthe administration of nanopolymer PEG-400 and complexwas lower than control values.At the same time, the AST activity in the serum of the first experimental group was at the control level.As for the others ones,nanopolymer PEG-400 and complexwere administered,the higher rates could be due to active penetration of these substances into cells and mitochondria, where this enzymewas localized. De Ritis Ratioincreased, so it certifies the active elimination of AST in the blood. The bilirubin level in the serum of experimental animals was higher than the level of control. Such changes in the blood parameters of experimental ratscan be considered asa minor disturbance of the liver structure and function.
On day 14 of the experiment, in comparison with day 7, the ALT activity in the serum of all rats groups resulted in a significant reduction, except for the first experimental group. The lowest activity rates were in the third experimental group and they corresponded to physiological values.During the experiment, the AST activity in the blood of all animals increased in comparison with the first study, but it didn’t go beyond physiological fluctuations.The maximum activity was determined after the administration of the traditional form of enrofloxacin. As for other experimental groups, they rates were a little lower.However, it can be assumed that enrofloxacin in its traditional formcan enter the bloodstream from the place of administration much more slowly than nanopolymerPEG-400 and complex enrofloxacin – nanopolymerPEG-400 and it can be metabolized in the livertissue.This fact can be described as an improvementof the speed of penetration and accumulation in cells of the antibiotic enrofloxacin combined with the nanopolymer PEG-400 for its transportation. De Ritis Ratio was higher in the studied rats. At the same time, the bilirubin level of all experimental animals decreased, but remained higher, as compared to controls.
21 days after the administration of the test substances, the ALT activity in the animals’ blood was going down. In the third experimental group, as well as in the control, the enzyme activity level in the blood was within physiological fluctuations, while in rats, injected with the antibiotic enrofloxacin and PEG-400 separately, the ALT activity was higher. On day 21of the experiment, the AST activity in the blood of all animals was at the physiological level. Meanwhile, the maximum value of the enzyme after the use of PEG-400 was a little lower than after the administration of the antibiotic enrofloxacin alone.At the same time it was lower after the complex enrofloxacin with nanopolymer PEG-400 administration.According to the dynamics of ALT/AST activity in the blood of animals, it may be concluded that the recovery of liver cells structure is faster in rats, injected with the complex enrofloxacin with nanopolymer PEG-400. The total bilirubin in the blood of all experimental groups has decreased. Thus, the obtained blood parameters can certify that three weeks after the administration of the antibiotic enrofloxacin, nanopolymer PEG-400 and complex enrofloxacin with PEG-400 the structure and the functional state of liver cellsrenewal process is going to start. The best results have been obtained after the use of complex enrofloxacin with PEG-400.
In the further research it is planned to study the effect of the enrofloxacin – nanopolymer PEG-400 complex on the functional state and the structure of other organs and systems of the body.
References
Padiyara, P., Inoue, H., & Sprenger, M. (2018). Global governance mechanisms to address antimicrobial resistance. Infectious Diseases: Research and Treatment, 11, 1178633718767887. https://doi.org/10.1177/1178633718767887
World Health Organization. (2019). Global action plan on antimicrobial resistance. Geneva: World Health Organization; 2015. Google Scholar.
Ardal, C., Outterson, K., Hoffman, S. J., Ghafur, A., Sharland, M., Ranganathan, N., Daulaire, N. (2016). International cooperation to improve access to and sustain effectiveness of antimicrobials. The Lancet, 387(10015), 296-307.
https://doi.org/10.1016/S0140-6736(15)00470-5
Shaker, M. A., & Shaaban, M. I. (2017). Formulation of carbapenems loaded gold nanoparticles to combat multi-antibiotic bacterial resistance: In vitro antibacterial study. International Journal of Pharmaceutics, 525(1), 71-84.
https://doi.org/10.1016/j.ijpharm.2017.04.019
Beyth, N., Houri-Haddad, Y., Domb, A., Khan, W., & Hazan, R. (2015). Alternative antimicrobial approach: nano-antimicrobial materials. Evidence-based complementary and alternative medicine, 2015. https://doi.org/10.1155/2015/246012
Varvarenko, S. M., Samaryk, V. V., Vlizlo, V. V., Ostapiv, D. D., Nosova, N. G., Tarnavchyk, I. T., Yaremchuk, I. N. (2015). Fluorescein-containing theranostics based on the pseudo-poly (amino acid) s for monitoring of drug delivery and release. Polymer Journal, 37(2), 193-199. https://doi.org/10.15407/polymerj.37.02.193
Chekh, B. O., Dron, I. A., Vynnytska, S. I., Oleksa, V. V., Atamaniuk, I. E., & Vlizlo, V. V. (2017). Antibacterial activity of complex of enrofloxacin with nanopolymer GluLa-DPG-PEG600. (19,№ 4), 83-87.
https://doi.org/10.15407/animbiol19.04.083
Radomska, A., Leszczyszyn, J., & Radomski, M. W. (2016). The nanopharmacology and nanotoxicology of nanomaterials: new opportunities and challenges. Advances in Clinical and Experimental Medicine, 25(1), 151-162.
https://doi.org/10.17219/acem/60879
Luo, Y., Hossain, M., Wang, C., Qiao, Y., An, J., Ma, L., & Su, M. (2013). Targeted nanoparticles for enhanced X-ray radiation killing of multidrug-resistant bacteria. Nanoscale, 5(2), 687-694.
https://doi.org/10.1039/C2NR33154C
Cheng, C. J., Tietjen, G. T., Saucier-Sawyer, J. K., & Saltzman, W. M. (2015). A holistic approach to targeting disease with polymeric nanoparticles. Nature reviews Drug discovery, 14(4), 239-247. https://doi.org/10.1038/nrd4503
Chekh, B. O., Ferens, M. V., OstapiV, D. D., Samaryk, V. Y., Varvarenko, S. M., & Vlizlo, V. V. (2017). Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats. The Ukrainian Biochemical Journal, (89,№ 4), 13-21. https://doi.org/10.15407/ubj89.04.013
Alekseev, K. V., Tikhonova, N. V., Blynskaya, E. V., Kurbusheva, E. Y., Turchinova, K. G., Mikheeva, A. S., Uvarov, N. A. (2012). Technology of increasing the biological and pharmaceutical accessibility of medicinal substances. Vestn. Nov. Med. Tekhnol, 19(4), 43-47.
Wang, J., Li, S., Han, Y., Guan, J., Chung, S., Wang, C., & Li, D. (2018). Poly (Ethylene Glycol)-polylactide micelles for cancer therapy. Frontiers in pharmacology, 9, 202.
https://doi.org/10.3389/fphar.2018.00202
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. - Vydavnytstvo Lvivskoi politekhniky, (886), 47-51.
Veterinary Clinical Biochemistry: Textbook, Levchenko,V. I. and Vlizlo, V. V, Bila Tserkva, 2019. 450 с
Vlizlo, V. V., Fedoruk, R. S., & Ratych, I. B. (2012). Laboratory methods of investigation in biology, stock-breeding and veterinary. by VV Vlizlo. Lviv: Spolom (in Ukrainian).
Levchenko, V., Vlizlo, V., Kondrakhin, I., Holovakha, V. Morozenko, D., Sakhniuk,V., Slivinska,L.,. ..&Bohatko, L. (2017). Clinical diagnostics of animal diseases.
Parliament, E. (2010). DIRECTIVE 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Book DIRECTIVE 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. City, 33-78.
Kliuchynska, T., Zalinian, Е., Verbova T. (2019). CREATION OF HISTORICAL CONTROL OF SERUM BIOCHEMISTRY PARAMETERS OF WISTAR HANNOVER RATS. State Enterprise "L. I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety", Ministry of Health of Ukraine, Kyiv, Ukraine.
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