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

Kończak O.; Zeyland J.; Radko L. · Journal of veterinary research · 2026

**Background & Methods** This in vitro review study evaluated the protective effects of cannabidiol (CBD) against nephrotoxicity induced by ionophore coccidiostats (lasalocid, monensin, and narasin) in human embryonic kidney (HEK-293) cells. Cells were exposed to each coccidiostat alone or in combination with CBD, with cytotoxicity assessed through mitochondrial activity, lysosomal activity, total protein content, and membrane integrity assays. Interaction analysis was performed to determine synergistic, additive, or antagonistic effects of CBD co-treatment. **Key Findings** • Ionophore coccidiostats induced dose-dependent cytotoxicity in HEK-293 cells, with lasalocid demonstrating the greatest toxicity, significantly impairing mitochondrial function and membrane integrity at 1 µg/mL concentration. • Co-treatment with cannabidiol significantly attenuated the toxic effects of all three coccidiostats, with predominantly antagonistic interactions observed, indicating a protective mechanism by CBD against ionophore-induced kidney cell damage. • Additive toxic effects were noted at high concentrations of the lasalocid-CBD combination, suggesting concentration-dependent variability in CBD's protective capacity. **Dosage & Administration** Specific doses and administration routes for therapeutic application are not reported. The study utilized varying in vitro concentrations of lasalocid, monensin, narasin, and CBD to establish dose-response relationships and interaction patterns. **Safety & Adverse Effects** Not reported. The study did not assess adverse effects or safety parameters in this in vitro model system. **Evidence Quality** This is an in vitro laboratory study with significant limitations regarding clinical applicability. Findings are restricted to a single human kidney cell line and do not account for complex physiological systems, metabolic processes, absorption, distribution, or elimination that occur in vivo. The authors acknowledge this limitation, calling for further in vivo studies to validate protective effects. The antagonistic interaction observed between CBD and coccidiostats suggests a genuine protective mechanism, though the additive toxicity at high lasalocid-CBD concentrations raises questions about optimal dosing thresholds. As a cell culture review study, this represents preliminary mechanistic evidence (Level IV) that requires confirmation through animal models and clinical investigation before clinical recommendations can be established.

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