Week_10_Selected_Nephrotoxicants

Week_10_Selected_Nephrotoxicants - Week 10 - Selected...

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Week 10 - Selected Nephrotoxicants Heavy Metals Many metals (e.g. cadmium, chromium, lead, mercury, platinum and uranium) are nephrotoxic. The nature and severity of nephrotoxicity depends upon the form of the metal. For example, inorganic mercury salts are more nephrotoxic than organic mercury compounds. Additionally, different metals have different primary targets within the kidney. Mercury Humans are environmentally exposed to elemental mercury vapor, inorganic mercurous and mercuric salts and organic mercuric compounds. Elemental mercury is rapidly oxidized in erthyrocytes or tissues to inorganic mercury and, thus, the tissue distributions of elemental and inorganic mercury are very similar. The kidneys are the primary target organs for accumulation of Hg 2+ and the proximal tubule is the initial site of toxicity. Cadmium Chronic exposure of (nonsmoking) humans to cadmium is primarily through food. Cadmium has a half-life of greater than 10 years in humans and thus accumulates in the body over time. Approximately 50% of the cadmium body burden can be found in the kidneys. Cadmium produces proximal tubule dysfunction and renal injury characterized by increases in urinary excretion of glucose, amino acids, calcium and cellular enzymes. An interesting aspect of cadmium nephrotoxicity is the role of metallothioneins. Metallothioneins are low molecular weight metal-binding proteins that have a high affinity for cadmium and other metals. The mechanism by which metallothionein is thought to mediate heavy metal toxicity is through its ability to bind the metal and thereby render it biologically inactive. This assumes that the unbound ('free') metal is the toxic species. Following exposure, cadmium is thought to reach the
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Week_10_Selected_Nephrotoxicants - Week 10 - Selected...

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