Toxicity of adenine nucleotides in the isolated perfused kidney: selective destruction of the S2 segment of the proximal tubule.
In an attempt to ameliorate the morphological abnormalities and decreased renal function produced by hypoxia in the isolated perfused rat kidney, adenosine triphosphate (ATP) was added to the perfusate medium. No improvement was noted in the histological changes or renal function. Paradoxically, however, in oxygenated control kidneys, ATP (2.5-10 mM), caused a severe injury remarkably limited to the S2 segments of proximal tubule. This injury was more destructive than that observed with complete ischemia for the same period of time or with inhibitors of glycolysis, intermediary metabolism, or respiratory chain function. Tubular damage produced by ATP was paradoxically prevented by hypoxia and mitochondrial inhibition. The mechanism of this selective toxic injury to the proximal tubule remains unclear and may depend upon intact transport metabolism of the cell.
Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Beth Israel Hospital, Department of Pathology, Boston, MA.
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D000244:Adenosine Diphosphate / Q000633:toxicity*; D000255:Adenosine Triphosphate / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007511:Ischemia / Q000139:chemically induced / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000502:physiology
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate