Multiple Effects of Chronic Low-Dose Cadmium Exposure on the Liver, Osteogenesis, and Hematopoiesis in Animals and Humans
Authors:   Dnipro State Medical University. 9, Vernadsky Str., office 51, Dnipro 49044, Ukraine, Zemlianyi O. A. , Gerasymchuk P. G. ,   Dnipro Medical Institute of Conventional and Alternative Medicine. 17, Sevastopolska St., Dnipro 49005, Ukraine, Zaitsev L. O. ,   Dnipro Medical Institute of Conventional and Alternative Medicine. 17, Sevastopolska St., Dnipro 49005, Ukraine, Mionchynsky D. O. ,   Dnipro Medical Institute of Conventional and Alternative Medicine. 17, Sevastopolska St., Dnipro 49005, Ukraine, Kharchenko O. I. ,   Dnipro Medical Institute of Conventional and Alternative Medicine. 17, Sevastopolska St., Dnipro 49005, Ukraine, Samoilenko I. I. ,   Dnipro Medical Institute of Conventional and Alternative Medicine. 17, Sevastopolska St., Dnipro 49005, Ukraine, Alekseenko V. V. ,   Dnipro Medical Institute of Conventional and Alternative Medicine. 17, Sevastopolska St., Dnipro 49005, Ukraine, Shemet S. A. ,   Public Organization Ukrainian Association for Hemophilia and Hemostasis" Factor D. 20, Housing microdistrict Topolya-3, Dnipro 49041,Ukraine
Published: October 2021

Cadmium salts are among the TOP-20 of the most dangerous compounds for animals in terms of toxicity. At the same time, today there is a paradigm shift in the studies of cadmium effects: in contrast to the acute effects of intoxication, more importance and practical relevance is attained by studying the continued chronic exposure to small cadmium doses (Chronic Low Cd Exposure) which can take place in real environmental conditions of industrially polluted regions and already impacts about 10% of the world population. While the early changes in kidneys and marker parameters of the urinary system under the action of cadmium are being studied quite actively, cadmium effects on other organs and systems in the body are insufficiently investigated. The purpose of the study was to analyse the multiple effects of cadmium on liver function, osteogenesis, haematopoiesis, and haemostasis in animals and humans. Protective mechanisms that reduce cadmium accumulation in hepatocytes compared to renal cells, in particular, the role of cellular transporters of biogenic metal ions (Fe2+, Zn2+, Mn2+, Cu2+), are systematized. Results and discussion. Cadmium mostly uses divalent metal transporter 1 and Zrt/Irt-like transporters, such as ZIP8 and ZIP14. Given the role of liver in the chelation and deposition of cadmium in the form of complexes with metallothioneins and glutathione, the significant potential of chelating and antioxidant hepatoprotectants to reduce negative effects is suggested. The role of exogenous chemical chelators and antioxidants in detoxifying cadmium is supported by the studies of other cadmium-binding molecules (glutathione, polyphenols, anthocyanins). Both direct effects of cadmium on the osteogenesis and calcium metabolism, and indirect effects on osteoblasts and osteoclasts are considered. In particular, current data on cadmium role in the development of endemic disease Itai-Itai in Japan is discussed. Notably, cadmium effect in children has a special hazards and long-term consequences. Data on cadmium role in interfering Ca2+ metabolism, particularly its effects on epithelial calcium channels (TRPV5) and Na-phosphate co-transporters (SLC34A1) are summarized. Conclusion. Current data suggest that chronic effects of cadmium in ultra-low concentrations upon the osteogenesis are even more evident than in renal system. A review of current data on cadmium effects upon the hematopoietic system in animal models is presented. The earliest studies found relation between cadmium and haemoglobin decrease, which could be mediated by interfering with intracellular Fe traffic, and effects on erythropoietin synthesis. Cadmium affected haemostasis and increased platelet aggregation. Animal studies suggest that chronic cadmium toxicity leads to hypercoagulation and increases the risks of thrombosis. Based on the summarized data, it is concluded that the investigating cadmium effects on hematopoiesis and hemostasis is a promising area for further studies of chronic low-dose cadmium exposure