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

Abstract

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