engleski

Cell mechanisms of heavy metal toxicity

Metals are natural constituents of the environment and their balance is obtained by both geologic and biologic cycles. Their utilization by humans in industry and agriculture has transformed many metals into potential health hazards. Some metals, such as cadmium (Cd), mercury (Hg), lead (Pb), arsenic (As) and platinum (Pt) (often termed as heavy metals), were found to be very toxic to mammals. Main exposure sources of these metals are air, food and water. Following absorption, they cause a variety of toxic effects in kidney, liver and reproductive tract, their major target organs, that result in respective dysfunctions. Nephrotoxicity in humans and experimental animals due to exposure to Cd, Hg and Pt is primarily manifested by impaired reabsorption and secretion in proximal tubules (PT). The main symptoms of heavy metal nephrotoxicity are found in urine, and include polyuria, proteinuria, phosphaturia, aminoaciduria, and glucosuria, indicating various brush-border membrane (BBM) transporters as being affected. As found in experimental Cd nephrotoxicity in rats, impaired functional capacity of the BBM in heavy metal nephrotoxicity may result from: a) direct inhibition of BBM transporters, b) shortening and loss of microvilli, and c) loss of specific transporters from the membrane. The loss of BBM transporters may be caused by impaired vesicle-mediated recycling of proteins in PT cells due to diminished expression of the vacuolar H+-ATPase and direct inhibition of its activity in intracellular organelles. In addition, Cd, Hg and Pt were found to affect the structure, polymerization state and abundance of cytoskeleton (actin filaments and microtubules) in PT cells, thus contributing to the impaired intracellular vesicle trafficking and preventing functional integration of proteins into the BBM. The experimental evidence in rats showed that similar cellular mechanisms of heavy metal toxicity may be involved in male reproductive tract, causing dysfunctions of the epithelium and impaired fertility.

cell membrane; kidney; nephrotoxicity

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