Zinc Supplementation Protects against Cadmium Accumulation and Cytotoxicity in Madin-Darby Bovine Kidney Cells

<div><p>Cadmium ions (Cd²⁺) have been reported to accumulate in bovine tissues, although Cd²⁺ cytotoxicity has not been investigated thoroughly in this species. Zinc ions (Zn²⁺) have been shown to antagonize the toxic effects of heavy metals such as Cd²⁺ in some systems. The present study investigated Cd²⁺ cytotoxicity in Madin-Darby bovine kidney (MDBK) epithelial cells, and explored whether this was modified by Zn²⁺. Exposure to Cd²⁺ led to a dose- and time-dependent increase in apoptotic cell death, with increased intracellular levels of reactive oxygen species and mitochondrial damage. Zn²⁺ supplementation alleviated Cd²⁺-induced cytotoxicity and this protective effect was more obvious when cells were exposed to a lower concentration of Cd²⁺ (10 μM), as compared to 50 μM Cd²⁺. This indicated that high levels of Cd²⁺ accumulation might induce irreversible damage in bovine kidney cells. Metallothioneins (MTs) are metal-binding proteins that play an essential role in heavy metal ion detoxification. We found that co-exposure to Zn²⁺ and Cd²⁺ synergistically enhanced RNA and protein expression of MT-1, MT-2, and the metal-regulatory transcription factor 1 in MDBK cells. Notably, addition of Zn²⁺ reduced the amounts of cytosolic Cd²⁺ detected following MDBK exposure to 10 μM Cd²⁺. These findings revealed a protective role of Zn²⁺ in counteracting Cd²⁺ uptake and toxicity in MDBK cells, indicating that this approach may provide a means to protect livestock from excessive Cd²⁺ accumulation.</p>