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

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.