Apoptotic pathways of oxidative damage to renal tubular epithelial cells.
Toxic renal failure induced by gentamicin, glycerol, or cisplatin, as well as ischemic renal failure in vivo and hypoxia/reoxygenation of tubular epithelial cells in vitro, induces the production of reactive oxygen metabolites (ROM). Generation of ROM is responsible for the induction of tubular epithelial cell death, which is mediated by caspases and/or endonucleases. Scavenging of ROM protects tubular epithelium from caspase and endonuclease activation and from cell death. Thus, the inhibition of ROM production combined with the pharmacological control of caspase and endonuclease pathways may provide future modalities in the prevention or treatment of acute renal failure in humans.
Basnakian
Alexei G
AG
University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Kaushal
Gur P
GP
Shah
Sudhir V
SV
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity; D004720:Endonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005839:Gentamicins / Q000633:toxicity; D005990:Glycerol / Q000633:toxicity; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005839:Gentamicins; D017382:Reactive Oxygen Species; D004720:Endonucleases; D020169:Caspases; D005990:Glycerol; D002945:Cisplatin