Iron-induced apoptosis in mouse renal proximal tubules after an injection of a renal carcinogen, iron-nitrilotriacetate.
Redox-active iron was demonstrated in mouse kidney by Timm's sulphide-silver staining after an injection of a renal carcinogen, iron-nitrilotriacetate (Fe-NTA). The iron was on the apical site of tubular epithelia of the renal proximal convoluted portion and in the tubules of the straight portion 30 min after the Fe-NTA injection. As the epithelial cells of the proximal tubules died, the iron disappeared in the dead cells and was stored in the cytoplasm of the more distal tubular epithelia. Biochemically, redox-active iron in the kidney rapidly increased to four times higher than the control 30 min after the Fe-NTA injection, then decreased to a plateau which was still higher than the control. Iron tightly stored in iron-storage proteins increased gradually by 3 h after the injection and then decreased at 5 h. The iron-induced free radical injuries, such as lipid peroxidation and protein oxidation, were demonstrated in the renal proximal tubules by histochemistry. The nuclei of the proximal tubular epithelia shrank and fragmented with the free radical injuries, and were positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling. DNA ladder was demonstrated in the mice renal cortexes by agarose gel electrophoresis. It was elucidated that redox-active iron caused free radical injuries in the proximal tubules of mice kidneys after the injection of a renal carcinogenic iron (Fe-NTA) and induced the apoptosis of the proximal tubular epithelial cells.
Kawabata
T
T
Department of Pathology, Okayama University Medical School, Shikata-cho, Japan.
Ma
Y
Y
Yamador
I
I
Okada
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity*; D005290:Ferric Compounds / Q000633:toxicity*; D005609:Free Radicals; D007501:Iron / Q000633:toxicity*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D011817:Rabbits
D002273:Carcinogens; D005290:Ferric Compounds; D005609:Free Radicals; D007501:Iron; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate