Humans are exposed intentionally and unintentionally to a variety of diverse chemicals that harm the kidney. As the list of drugs, natural products, industrial chemicals and environmental pollutants that cause nephrotoxicity has increased, it has become clear that chemicals with very diverse chemical structures produce nephrotoxicity. For example, the heavy metal HgCl2, the myco-toxin fumonisin B1, the immunosuppresant cyclosporin A, and the aminoglycoside antibiotics all produce acute renal failure but are not structurally related. Thus, it is not surprising that the cellular targets within the kidney and the mechanisms of cellular injury vary with different toxicants. Nevertheless, there are similarities between chemical-induced acute tubular injury and ischemia/reperfusion injury.
The tubular cells of the kidney are particularly vulnerable to toxicant-mediated injury due to their disproportionate exposure to circulating chemicals and transport processes that result in high intracellu-lar concentrations. It is generally thought that the parent chemical or a metabolite initiates toxicity through its covalent or noncovalent binding to cellular macromolecules or through their ability to produce reactive oxygen species. In either case the activity of the macromole-cule(s) is altered resulting in cell injury. For example, proteins and lipids in the plasma membrane, nucleus, lysosome, mitochondrion and cytosol are all targets of toxicants. If the toxicant causes oxidative stress both lipid peroxidation and protein oxidation have been shown to contribute to cell injury.
In many cases mitochondria are a critical target and the lack of adenosine triphosphate (ATP) leads to cell injury due to the dependence of renal function on aerobic metabolism. The loss of ATP leads
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