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 organ s of the male Wistar rat urogenital system, 48 h after cadmium adminis tration ip at a dose of 0.03 mmol/kg. Characteristic DNA fragmentation (as measured by an enzyme-linked immunosorbent assay, ELISA) and hist opathologically observed changes characteristic of apoptosis are found in the kidney, prostate, seminal vesicles, testes, and epididymis. TU NEL assay also demonstrates the apoptosis. Such changes are absent fro m bladder and vas deferens tissue. Timely administration of an appropr iate chelating agent capable of reaching intracellular cadmium binding sites can suppress the processes leading to apoptosis. Administration of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS, 0.5 mmol/kg ipi to cadmium treated rats is effective in greatly reducing typical hist opathologic signs of apoptosis and the associated chromatin DNA fragme ntation as revealed by ELISA when the antagonist is administered 1 h a fter cadmium. Administration of the chelating agent at later times res ults in greater degradation of DNA into oligonucleotides and more prom inent histopathological evidence of apoptotic changes in the affected organs of the rat urogenital system. There is also a progressive incre ase in apoptotic changes indicated by TUNEL assay, as the antagonist i s administered at progressively greater intervals after cadmium.