Protective effects of cannabidiol against nephrotoxicity of ionophore coccidiostats in HEK-293 cells

Oliwia Maria Kończak; Joanna Zeyland; Lidia Radko

doi:10.2478/jvetres-2026-0047

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Protective effects of cannabidiol against nephrotoxicity of ionophore coccidiostats in HEK-293 cells

Journal of Veterinary Research

AHEAD OF PRINT

By: Oliwia Maria Kończak , Joanna Zeyland and Lidia Radko

Open Access

|Aug 2026

Abstract

Introduction

Veterinary drug residues in the environment threaten public health and animal welfare. Ionophore coccidiostats (lasalocid (LAS), monensin (MON) and narasin (NAR)) are commonly used in animal production. Overdosing, errors in feed mixing or interactions with other drugs can cause nephrotoxicity in animals, which has also been observed in poisoned humans. The toxic effects of veterinary drugs may be mitigated by cannabidiol (CBD), known to be antioxidant and cytoprotective and expected to have a protective effect on kidney cells. The aim of this study was to evaluate the effect of CBD on cytotoxicity induced by ionophore coccidiostats in human embryonic kidney cells (HEK-293).

Material and Methods

Cells were exposed to LAS, MON and NAR, either alone or in combination with CBD. Cytotoxicity was assessed using mitochondrial activity, lysosomal activity, total protein content and membrane integrity assays. The action of combination of CBD and the coccidiostats was determined using interaction analysis.

Results

The ionophores induced cytotoxicity dose-dependently. Lasalocid was the most toxic, significantly impairing mitochondrial function and membrane integrity at 1 µg/mL. Co-treatment with CBD significantly attenuated the drugs’ toxic effects. Predominantly, antagonistic effects were revealed, indicating a protective effect of CBD. However, an additive effect was observed at high concentrations of the LAS-CBD combination.

Conclusion

Cannabidiol exerts a protective effect against coccidiostat nephrotoxicity in human renal cells. This finding suggests its modulation of cellular responses to ionophore-induced cytotoxicity, offering a basis for further in vivo studies on its potential.

References

Babić M., Petrović Z., Borjan N., Krnjaja O., Gavrilović D., Silađi Č., Tanković S.: Coccidiostat residues in withdrawal feed for broilers – implications of cross-contamination in feed production lines. Meat Technol 2025, 66, 529–533, doi: 10.18485/meattech.2025.66.3.91.
Open DOI Search in Google Scholar Back to article
Bello A., Henri J., Viel A., Mochel J.P., Poźniak B.: Ionophore coccidiostats – disposition kinetics in laying hens and residues transfer to eggs. Poult Sci 2023, 102, 102280, doi: 10.1016/j.psj.2022.102280
Open DOI Search in Google Scholar Back to article
Blain M., Garrard A., Poppenga R., Chen B., Valento M., Halliday Gittinger M.: Survival after severe rhabdomyolysis following monensin ingestion. J Med Toxicol 2017, 13, 241–245, doi: 10.1007/s13181-017-0616-6.
Open DOI Search in Google Scholar Back to article
Bosch L., Bersenas A.M., Bateman S.: Acute polyneuromyopathy with respiratory failure secondary to monensin intoxication in a dog. J Vet Emerg Crit Care 2017, 27, 711–717, doi: 10.1111/vec.12684.
Open DOI Search in Google Scholar Back to article
Caldeira C., Neves W.S., Cury P.M., Serrano P., Baptista M.A.S.F., Burdmann E.A.: Rhabdomyolysis, acute renal failure, and death after monensin ingestion. Am J Kidney Dis 2001, 38, 1108–1112, doi: 10.1053/ajkd.2001.28618.
Open DOI Search in Google Scholar Back to article
Chou T.-C., Talalay P.: Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv Enzym Regul 1984, 22, 27–55, doi: 10.1016/0065 2571(84)90007-4.
Open DOI Search in Google Scholar Back to article
Cybulski W., Radko L., Rzeski W.: Cytotoxicity of monensin, narasin and salinomycin and their interaction with silybin in HepG2, LMH and L6 cell cultures. Toxicol In Vitro 2015, 29, 1466–1473, doi: 10.1016/j.tiv.2014.11.013.
Open DOI Search in Google Scholar Back to article
Damir H., Alhaj Ali M., Abbas T.A., Omer E.A., Al Fihail A.M.: Narasin poisoning in the dromedary camel (Camelus dromedarius). Comp Clin Pathol 2013, 22, 305–311, doi: 10.1007/s00580-011-1403-4.
Open DOI Search in Google Scholar Back to article
Decloedt A., Verheyen T., De Clercq D., Sys S., Vercauteren G., Ducatelle R., van Loon G.: Acute and long-term cardiomyopathy and delayed neurotoxicity after accidental lasalocid poisoning in horses. J Vet Intern Med 2012, 26, 1005–1011, doi: 10.1111/j.1939-1676.2012.00933.x.
Open DOI Search in Google Scholar Back to article
Deljou M., Aslani M.R., Mohri M., Movassaghi A.R., Heidarpour M.: Clinical, laboratory and pathological findings in sub-acute monensin intoxication in goats. Vet Res Forum 2014, 5, 161–167.
Search in Google Scholar Back to article
Ekinci İ.B., Chłodowska A., Olejnik M.: Ionophore toxicity in animals: A review of clinical and molecular aspects. Int J Mol Sci 2023, 24, 1696, doi: 10.3390/ijms24021696.
Open DOI Search in Google Scholar Back to article
Gaweł A., Mazurkiewicz M.: Przebieg zatrucia narazyną w stadzie indyków rzeźnych (Narasin poisoning in a flock of slaughter turkeys – in Polish). Med Weter 2004, 60, 154–159.
Search in Google Scholar Back to article
Ghovanloo M.R., Goodchild S.J., Ruben P.C.: Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study. PLoS One 2022, 17, e0271801, doi: 10.1371/journal.pone.0271801.
Open DOI Search in Google Scholar Back to article
Jans D.A., Jans P., Luzius H., Fahrenholz F.: Monensin-resistant LLC-PK1 cell mutants are affected in recycling of the adenylate cyclase-stimulating vasopressin Endocrinol 1991, 81, V2-receptor. Mol Cell 165–174, doi: 10.1016/0303 7207(91)90215-e.
Open DOI Search in Google Scholar Back to article
Jung K.Y., Uchida S., Endou H.: Nephrotoxicity assessment by measuring cellular ATP content. I. Substrate specificities in the maintenance of ATP content in isolated rat nephron segments. Toxicol Appl Pharmacol 1989, 100, 369–382, doi: 10.1016/0041 008x8990285-8.
Open DOI Search in Google Scholar Back to article
Kim J.L., Kim B.R., Kim D.Y., Jeong Y.A., Jeong S., Na Y.J., Park S.H., Yun H.K., Jo M.J., Kim B.G., Kim H.D., Kim D.H., Oh S.C., Lee S.I., Lee D.-H.: Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer. Cancers 2019, 11, 625, doi: 10.3390/cancers11050642.
Open DOI Search in Google Scholar Back to article
Kouyoumdjian J.A., Morita M.P.A., Sato A.K., Pissolatti A.F.: Fatal rhabdomyolysis after acute sodium monensin (Rumensin®) toxicity: case report. Arq Neuro-Psiquiatr 2001, 59, 596–598, doi: 10.1590/S0004-282X2001000400022.
Open DOI Search in Google Scholar Back to article
Martins R.R., Pereira A.M.P.T., Silva L.J.G., Esteves A., Duarte S.C., Freitas A., Pena A.: Risk assessment of nine coccidiostats in commercial and home-raised eggs. Foods 2023, 12, 1225, doi: 10.3390/foods12061225.
Open DOI Search in Google Scholar Back to article
Mortier L., Huet A.-C., Charlier C., Daeseleire E., Delahaut P., Van Peteghem C.: Incidence of residues of nine anticoccidials in eggs. Food Addit Contam 2005, 22, 1120–1125, doi: 10.1080/02652030500199355.
Open DOI Search in Google Scholar Back to article
Pan H., Mukhopadhyay P., Rajesh M., Patel V., Mukhopadhyay B., Gao B., Haskó G., Pacher P.: Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. J Pharmacol Exp Ther 2009, 328, 708–714, doi: 10.1124/jpet.108.147181.
Open DOI Search in Google Scholar Back to article
Pankowska E., Kończak O., Żakowicz P., Wojciechowicz T., Gogulski M., Radko L.: Protective action of cannabidiol on tiamulin toxicity in humans—in vitro study. Int J Mol Sci 2024, 25, 13542, doi: 10.3390/ijms252413542.
Open DOI Search in Google Scholar Back to article
Park W.H., Jung C.W., Park J.O., Kim K., Kim W.S., Im Y.H., Lee M.H., Kang W.K., Park K.: Monensin inhibits the growth of renal cell carcinoma cells via cell cycle arrest or apoptosis. Int J Oncol 2003, 22, 855–860, doi: 10.3892/ijo.22.4.855.
Open DOI Search in Google Scholar Back to article
Preisig P.A., Alpern R.J., Hebert S.C.: Opossum kidney cells: A polarized renal epithelial cell line. Am J Physiol 1988, 255, F279–F288.
Search in Google Scholar Back to article
Radko L., Cybulski W., Rzeski W.: Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells. Pol J Vet Sci 2013, 16, 275–282, doi: 10.2478/pjvs-2013-0038.
Open DOI Search in Google Scholar Back to article
Radko L., Wojciechowicz T., Kończak O., Żakowicz P., Łętowski O., Salmanowicz J., Skrzypczak Z.: The action of cannabidiol on doxycycline cytotoxicity in human cells—in-vitro study. Molecules 2025, 30, 4319, doi: 10.3390/molecules30214319.
Open DOI Search in Google Scholar Back to article
Segev G., Baneth G., Levitin B., Aroch I., Shlosberg I.: Accidental poisoning of 17 dogs with lasalocid. Vet Rec 2004, 155, 174–176, doi: 10.1136/vr.155.6.174.
Open DOI Search in Google Scholar Back to article
Stewart J.R., Kenny A.J.: Proteins of the kidney microvillar membrane. Effects of monensin, vinblastine, swainsonine and glucosamine on the processing and assembly of endopeptidase 24.11 and dipeptidyl peptidase IV in pig kidney slices. Biochem J 1984, 224, 559–568, doi: 10.1042/bj2240559.
Open DOI Search in Google Scholar Back to article
Śledziński P., Nowak-Terpiłowska A., Rzymski P., Słomski R., Zeyland J.: In vitro evidence of selective pro-apoptotic action of the pure cannabidiol and cannabidiol-rich extract. Molecules 2023, 28, 7887, doi: 10.3390/molecules28237887.
Open DOI Search in Google Scholar Back to article
Vadizadeh A., Salehcheh M., Kalantar H., Khorsandi L., Rashno M., Mahdavinia M.: Cannabidiol attenuates arsenic induced nephrotoxicity via the NOX4 and NF-κB pathways in mice. Res Pharm Sci 2024, 19, 447–458, doi: 10.4103/RPS.RPS_51_24.
Open DOI Search in Google Scholar Back to article
Verma S.P., Das P.: Monensin induces cell death by autophagy and inhibits matrix metalloproteinase 7 (MMP7) in UOK146 renal cell carcinoma cell line. In Vitro Cell Dev Biol Anim 2018, 54, 736–742, doi: 10.1007/s11626-018-0298-7
Open DOI Search in Google Scholar Back to article
Zhang Z., Cui S., Zhang J.: Rhabdomyolysis and hepatotoxicity following accidental monensin ingestion: A report of two cases. Toxicol Ind Health 2021, 37, 34-37, doi: 10.1177/0748233720974128.
Open DOI Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.2478/jvetres-2026-0047 | Journal eISSN: 2450-8608 (formerly 2300-3235)

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Language: English

Submitted on: Mar 9, 2026

Accepted on: Aug 20, 2026

Published on: Aug 24, 2026

Published by: National Veterinary Research Institute in Pulawy

In partnership with: Paradigm Publishing Services

Keywords:

Related subjects:

Microbiology and virology,

Life sciences, other,

Medicine,

Veterinary medicine

© 2026 Oliwia Maria Kończak, Joanna Zeyland, Lidia Radko, published by National Veterinary Research Institute in Pulawy
This work is licensed under the Creative Commons Attribution 4.0 License.

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