Cadmium-induced apoptosis in the urogenital organs of the male rat and its suppression by chelation.
Cadmium-induced apoptosis is shown to occur, in vivo, in several organs of the male Wistar rat urogenital system, 48 h after cadmium administration i.p. at a dose of 0.03 mmol/kg. Characteristic DNA fragmentation (as measured by an enzyme-linked immunosorbent-assay, ELISA) and histopathologically observed changes characteristic of apoptosis are found in the kidney, prostate, seminal vesicles, testes, and epididymis. TUNEL assay also demonstrates the apoptosis. Such changes are absent from bladder and vas deferens tissue. Timely administration of an appropriate chelating agent capable of reaching intracellular cadmium binding sites can suppress the processes leading to apoptosis. Administration of monoisomyl meso-2,3-dimercaptosuccinate (Mi-ADMS, 0.5 mmol/kg i.p.) to cadmium-treated rats is effective in greatly reducing typical histopathologic signs of apoptosis and the associated chromatin DNA fragmentation as revealed by ELISA when the antagonist is administered 1 h after cadmium. Administration of the chelating agent at law times results in greater degradation of DNA into oligonucleotides and more prominent histopathological evidence of apoptotic changes in the affected organs of the rat urogenital system. There is also a progressive increase in apoptotic changes indicated by TUNEL assay, as the antagonist is administered at progressively greater intervals after cadmium.
Yan
H
H
Department of Biology, Vanderbilt University, Nashville, Tennessee 37235, USA.
Carter
C E
CE
Xu
C
C
Singh
P K
PK
Jones
M M
MM
Johnson
J E
JE
Dietrich
M S
MS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001710:Biotin; D019256:Cadmium Chloride / Q000633:toxicity*; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation; D004253:DNA Nucleotidylexotransferase; D004797:Enzyme-Linked Immunosorbent Assay; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D004113:Succimer / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014544:Uridine Triphosphate; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D014566:Urogenital System / Q000187:drug effects*
D002614:Chelating Agents; D002843:Chromatin; D009153:Mutagens; D001710:Biotin; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; D004253:DNA Nucleotidylexotransferase; D019256:Cadmium Chloride; D014544:Uridine Triphosphate