Emmy Van Kerkhove

Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative stress depends on the dose, duration and frequency of Cd exposure. Also the presence or absence of serum in experimental conditions, type of cells and their antioxidant capacity, as well as the speciation of Cd are important determinants. At the cellular level, the Cd-induced oxidative stress either leads to oxidative damage or activates signal transduction pathways to initiate defence responses. This balance is important on how different organ systems respond to Cd stress and ultimately define the pathological outcome. In this review, we highlight the Cd-induced oxidant/antioxidant status as well as the damage versus signalling scenario in relation to Cd toxicity. Emphasis is addressed to Cd-induced pathologies of major target organs, including a section on cell proliferation and carcinogenesis. Furthermore, attention is paid to Cd-induced oxidative stress in undifferentiated stem cells, which can provide information for future therapies in preventing Cd-induced pathologies.

Urinary kidney injury molecule 1 is a recently discovered early biomarker for renal damage that has been proven to be correlated to urinary cadmium in rats. However, so far the association between urinary cadmium and kidney injury molecule 1 in humans after long-term, low-dose cadmium exposure has not been studied.

Toxic metals such as cadmium (Cd²⁺) pose serious risks to human health. However, even though the importance of Cd²⁺ as environmental health hazards is now widely appreciated, the specific mechanisms by which it produces its adverse effects have yet to be fully elucidated. Cd²⁺ is known to enter cells, it binds and interacts with a multitude of molecules, it may indirectly induce oxidative stress and interfere with gene expression and repair of DNA. It also interacts with transport across cell membranes and epithelia and may therefore disturb the cell’s homeostasis and function. Interaction with epithelial transport, especially in the kidney and the liver, may have serious consequences in general health. A lot of research still needs to be done to understand the exact way in which Cd²⁺ interferes with these transport phenomena. It is not always clear whether Cd²⁺ has primary or secondary effects on cell membrane transport. In the present review we try to summarize the work that has been done up to now and to critically discuss the relevance of the experimental work in vitro with respect to the in vivo situation.