TY - JOUR
T1 - A hypoxia-driven occurrence of chronic kidney disease and osteoporosis in COPD individuals
T2 - New insights into environmental cadmium exposure
AU - Cirovic, Aleksandar
AU - Denic, Aleksandar
AU - Clarke, Bart L.
AU - Vassallo, Robert
AU - Cirovic, Ana
AU - Landry, Greg M.
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/12
Y1 - 2022/12
N2 - Humans are exposed to cadmium via a variety of anthropogenic and natural pathways. Hypoxia, a key pathophysiological consequence of chronic obstructive pulmonary disease (COPD), as well as anemia, induce expression of many genes, including divalent metal transporter (DMT-1), to induce cell adaptation to decreased pO2. DMT-1 then becomes increasingly expressed in a majority of organs, specifically the duodenum and the kidney. DMT-1 serves as an iron transporter; however, it can transport other physiologically important elements, including manganese (Mn2+) and zinc (Zn2+), as well as highly toxic divalent cations such as cadmium (Cd2+). Chronic obstructive pulmonary disease (COPD) is a highly prevalent, non-communicable disease in populations > 40 years of age, and is a leading cause of death worldwide. Occurrence of comorbidities accompanying COPD, such as chronic kidney disease (CKD) and osteoporosis increase the mortality rate and costs of treatment. As cadmium has been shown to be significantly osteo- and nephrotoxic, its hazardous effects could deteriorate bone microarchitecture and decrease kidney function positioning it as a likely environmental contributor to comorbidity development. In this review, we highlight the important contribution of hypoxia-induced DMT-1 expression mediating a cadmium (Cd2+) overload-induced CKD and osteoporosis axes. Furthermore, individuals who suffer from chronic lung disease with hypoxic respiratory failure, such as severe COPD appear to be significantly more sensitive to cadmium toxicity than healthy individuals.
AB - Humans are exposed to cadmium via a variety of anthropogenic and natural pathways. Hypoxia, a key pathophysiological consequence of chronic obstructive pulmonary disease (COPD), as well as anemia, induce expression of many genes, including divalent metal transporter (DMT-1), to induce cell adaptation to decreased pO2. DMT-1 then becomes increasingly expressed in a majority of organs, specifically the duodenum and the kidney. DMT-1 serves as an iron transporter; however, it can transport other physiologically important elements, including manganese (Mn2+) and zinc (Zn2+), as well as highly toxic divalent cations such as cadmium (Cd2+). Chronic obstructive pulmonary disease (COPD) is a highly prevalent, non-communicable disease in populations > 40 years of age, and is a leading cause of death worldwide. Occurrence of comorbidities accompanying COPD, such as chronic kidney disease (CKD) and osteoporosis increase the mortality rate and costs of treatment. As cadmium has been shown to be significantly osteo- and nephrotoxic, its hazardous effects could deteriorate bone microarchitecture and decrease kidney function positioning it as a likely environmental contributor to comorbidity development. In this review, we highlight the important contribution of hypoxia-induced DMT-1 expression mediating a cadmium (Cd2+) overload-induced CKD and osteoporosis axes. Furthermore, individuals who suffer from chronic lung disease with hypoxic respiratory failure, such as severe COPD appear to be significantly more sensitive to cadmium toxicity than healthy individuals.
KW - Cadmium
KW - Chronic kidney disease
KW - Chronic obstructive pulmonary disease
KW - Divalent metal transporter 1
KW - Hypoxia
KW - Osteoporosis
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U2 - 10.1016/j.tox.2022.153355
DO - 10.1016/j.tox.2022.153355
M3 - Review article
C2 - 36265524
AN - SCOPUS:85140436100
SN - 0300-483X
VL - 482
JO - Toxicology
JF - Toxicology
M1 - 153355
ER -