Abstract

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.

Highlights

  • Cadmium (Cd) is a heavy metal that is extensively used in the manufacture of alloys, pigments, electroplates, and batteries

  • This study demonstrated that Cd2+ exposure was cytotoxic to a bovine cell line (MDBK) and indicated that Zn2+ supplementation had protective effects against this Cd2+-mediated cytotoxicity

  • Triggered Madin-Darby bovine kidney (MDBK) apoptotic cell death in a time- and dosedependent manner. This was associated with a Cd2+-induced increase in reactive oxygen species (ROS) accumulation in these cells, and mitochondrial depolarization

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Summary

Introduction

Cadmium (Cd) is a heavy metal that is extensively used in the manufacture of alloys, pigments, electroplates, and batteries. The toxic effects of free cadmium ions (Cd2+) have been studied intensively in humans, and effects on a wide range of organs have been reported, including the liver, bones, kidneys, and the reproductive, neurological, and immunological system [1,2]. The kidney and skeleton are most affected by chronic Cd2+ toxicity. Around 50% of the absorbed Cd2+ accumulates in the kidneys, and syndromes associated with Cd2+-induced renal damage include impaired vitamin metabolism, proteinuria, and loss of bone calcium [4]. Cd2+ accumulation to levels high enough to cause toxic effects in humans was reported in a polish study of cattle in 1999 [6]

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