Common mechanisms in nephropathy induced by toxic metals.
Various metals of unknown function in the body (Cd, Cr, Hg, Pb, U), trace elements in excessive concentrations (Co, Cu, Fe, Zn), or metals used in cancer therapy (Pt, V), accumulate in the mammalian kidney, largely in the proximal tubule (PT) cells, and cause functional and structural damage that results in reabsorptive and secretory defects. The intracellular mechanisms of their toxicity in the PT cells are not well known. Recent studies have indicated an oxidative stress with associated lipid peroxidation, apoptosis, and necrosis as common phenomena in the course of nephrotoxicity of these metals. However, a number of other phenomena, such as the selective inhibition and/or loss of various membrane transporters, enhancement of ion conductances, increased cytoplasmic concentration of calcium, deranged cytoskeleton and cell polarity, impaired endocytosis, swelling and fragmentation of mitochondria, increased expression of metallothionein, heat-shock and multidrug resistance proteins, loss of cell membrane integrity, as well as the damage of mitochondrial and genomic DNAs have been fragmentarily demonstrated for the action of some toxic metals, but their importance for the course of nephrotoxicity and the sequence of events in relation to oxidative stress, apoptosis, and necrosis have not been clearly established. Recent studies of metal toxicity in various tissues and cells of non-renal and renal origin enable us to estimate 'causes and consequences' of various phenomena in the metal-induced nephrotoxicity, and to assemble them in a possible common, time-related sequence.
Sabolić
Ivan
I
Unit of Molecular Toxicology, Institute for Medical Research and Occupational Health, Zagreb, Croatia. sabolic@imi.hr
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D019216:Metals, Heavy / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
D019216:Metals, Heavy