Abstract
The overuse of antibiotics in both humans and livestock has led to the antibiotic resistance phenomenon which is now considered one of the biggest problems in the modern world. Some antibiotics used to control or prevent infections in livestock poultry were registered a long time ago, and as a result, data on the possible side effects of their use, both for birds and humans, are incomplete and should be updated. An example of such an antibiotic is enrofloxacin which has been widely used in poultry since 1989. Data in recent years have begun to indicate that this antibiotic induces the process of apoptosis in diverse types of eukaryotic cells. Unfortunately, such studies have never been conducted on chicken models even though it is in poultry that this antibiotic is most commonly used. Therefore, the purpose of this work was to investigate whether enrofloxacin induces apoptosis in chicken cells of the UMNSAH/DF-1 line and to study the molecular mechanism of its action. The results of these experiments indicated that enrofloxacin induces apoptosis in chicken cells but not in human HEK-293 and PC3 cells. This induction was accompanied by changes in the morphology and size of mitochondria, the process of apoptosome formation and activation of executive caspases, which clearly indicates the role of the mitochondrial pathway in the induction of apoptosis by enrofloxacin. This study is the first to show the toxicity of enrofloxacin against chicken cells and to demonstrate the exact mechanism of its action. The results presented in this work show the need to monitor the concentration of antibiotic residues in poultry foods as well as to study their impact on public health to guarantee consumer safety and prevent the phenomenon of antibiotic resistance in bacteria.
Similar content being viewed by others
Data availability
Raw data are available from the authors upon request.
References
Scheer M (1987) Studies on the antibacterial activity of Baytril (Enrofloxacin). Vet Med Rev 2(1):90–99
Maślanka T, Jaroszewski JJ, Mikołajczyk A, Rotkiewicz T (2009) Effect of increasing doses of enrofloxacin on chicken articular cartilage. Pol J Vet Sci 12(1):21–33 PMID: 19459436
Huang J, Liao L, Wang G, Du Z, Wu Z (2023) Reproductive toxicity of enrofloxacin in Caenorhabditis elegans involves oxidative stress-induced cell apoptosis. J Environ Sci (China) 127:726–737. https://doi.org/10.1016/j.jes.2022.07.002
Ahadi H, Emami S (2020) Modification of 7-piperazinylquinolone antibacterials to promising anticancer lead compounds: synthesis and in vitro studies. Eur J Med Chem 187:111970. https://doi.org/10.1016/j.ejmech.2019.111970
Siengdee P, Euppayo T, Buddhachat K, Chomdej S, Nganvongpanit K (2016) Two fluoroquinolones and their combinations with hyaluronan: comparison of effects on canine chondrocyte culture. J Vet Pharmacol Ther 39(5):439–451. https://doi.org/10.1111/jvp.12305
Khazaeel K, Mazaheri Y, Hashemi Tabar M, Najafzadeh H, Morovvati H, Ghadrdan A (2015) Effect of Enrofloxacin on histochemistry, immunohistochemistry and molecular changes in Lamb articular cartilage. Acta Med Iran 53(9):555–561 PMID: 26553083
Liu B, Cui Y, Brown PB, Ge X, Xie J, Xu P (2015) Cytotoxic effects and apoptosis induction of enrofloxacin in hepatic cell line of grass carp (Ctenopharyngodon Idellus). Fish Shellfish Immunol 47(2):639–644. https://doi.org/10.1016/j.fsi.2015.10.007
Ding X, Jiang S, Li X, Wang Y, Zheng Z, Qin Y (2022) Cytotoxicity and apoptosis induced by enrofloxacin in loach fin cells in vitro. Comp Biochem Physiol C Toxicol Pharmacol 259:109398. https://doi.org/10.1016/j.cbpc.2022.109398
Jia D, You X, Tang M, Lyu Y, Hu J, Sun W (2023) Single and combined genotoxicity of metals and fluoroquinolones to zebrafish embryos at environmentally relevant concentrations. Aquat Toxicol 258:106495. https://doi.org/10.1016/j.aquatox.2023.106495
Zhivotovsky B, Orrenius S (2010) Cell death mechanisms: cross-talk and role in disease. Exp Cell Res 316(8):1374–1383. https://doi.org/10.1016/j.yexcr.2010.02.037
Kroemer G, Martin SJ (2005) Caspase-independent cell death. Nat Med 11:725–730. https://doi.org/10.1038/nm1263
Li J, Yuan J (2008) Caspases in apoptosis and beyond. Oncogene 27:6194–6206. https://doi.org/10.1038/onc.2008.297
Sessler T, Healy S, Samali A, Szegezdi E (2013) Structural determinants of DISC function: new insights into death receptor-mediated apoptosis signaling. Pharmacol Ther 140(2):186–199. https://doi.org/10.1016/j.pharmthera.2013.06.009
Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87(1):99–163. https://doi.org/10.1152/physrev.00013.2006
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91(4):479–489. https://doi.org/10.1016/s0092-8674(00)80434-1
Agyare C, Boamah VE, Zumbi CN, Osei FB (2019) Antibiotic Use in Poultry Production and Its Effects on Bacterial Resistance in: Antimicrobial Resistance - A Global; Threat Kumar, Yashwant, editor. IntechOpen ISBN: 978-1-78985-784-9, https://doi.org/10.5772/intechopen.73725
Grabowski Ł, Gaffke L, Pierzynowska K, Cyske Z, Choszcz M, Węgrzyn G, Węgrzyn A (2022) Enrofloxacin-the ruthless killer of eukaryotic cells or the last Hope in the fight against bacterial infections? Int J Mol Sci 23(7):3648. https://doi.org/10.3390/ijms23073648
Pena A, Silva LJ, Pereira A, Meisel L, Lino CM (2010) Determination of fluoroquinolone residues in poultry muscle in Portugal. Anal Bioanal Chem 397(6):2615–2621. https://doi.org/10.1007/s00216-010-3819-0
Muaz K, Riaz M, Akhtar S, Park S, Ismail A (2018) Antibiotic residues in Chicken meat: global prevalence, threats, and decontamination strategies: a review. J Food Prot 81(4):619–627. https://doi.org/10.4315/0362-028X.JFP-17-086
Teglia CM, Guiñez M, Culzoni MJ, Cerutti S (2021) Determination of residual enrofloxacin in eggs due to long term administration to laying hens. Analysis of the consumer exposure assessment to egg derivatives. Food Chem 351:129279. https://doi.org/10.1016/j.foodchem.2021.129279
Gbylik-Sikorska M, Łebkowska-Wieruszewska B, Gajda A, Nowacka-Kozak E, Lisowski A, Posyniak A (2021) Transfer of enrofloxacin, ciprofloxacin, and lincomycin into eggshells and residue depletion in egg components after multiple oral administration to laying hens. Poult Sci 100(9):101341. https://doi.org/10.1016/j.psj.2021.101341
Lu N, Bu M, Zhang C, Gao Q, Wang X, Zhou X, Ding D, Zhang H (2023) Development of a rapid detection method for enrofloxacin in food. Biotechnol Genet Eng Rev 21:1–19. https://doi.org/10.1080/02648725.2023.2204701
Wu S, Mao J, Zhang Y, Wang S, Huo M, Guo H (2023) Sensitive electrochemical detection of enrofloxacin in eggs based on carboxylated multi-walled carbon nanotubes-reduced graphene oxide nanocomposites: molecularly imprinted recognition versus direct electrocatalytic oxidation. Food Chem 413:135579. https://doi.org/10.1016/j.foodchem.2023.135579
Funding
This research was funded by the Institute of Biochemistry and Biophyscis, Polish Academy of Sciences (Poland), grant no. SBM-04/21 to ŁG.
Author information
Authors and Affiliations
Contributions
Conceptualization: ŁG and KP,; Methodology: ŁG, AW, GW, KP; Formal analysis and investigation: ŁG, MC, KW, LG, DN, MP; Writing - original draft preparation: ŁG, GW, KP; Writing - review and editing: GW, KP; Funding acquisition: ŁG; Supervision: GW, KP.
Corresponding author
Ethics declarations
Ethical approval
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Grabowski, Ł., Choszcz, M., Wiśniewska, K. et al. Induction of the mitochondrial pathway of apoptosis by enrofloxacin in the context of the safety issue of its use in poultry. Apoptosis (2024). https://doi.org/10.1007/s10495-024-01937-6
Accepted:
Published:
DOI: https://doi.org/10.1007/s10495-024-01937-6