CADMIUM-INDUCED APOPTOSIS IN THE UROGENITAL ORGANS OF THE MALE RAT AND ITS SUPPRESSION BY CHELATION

Abstract

Cadmium-induced apoptosis is shown to occur, in vivo, in several organs of the male Wistar rat urogenital system, 48 h after cadmium administration ip 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 monoisoamyl meso-2,3-dimercaptosuccinate (M\-ADMS, 0.5 mmol/kg ip) 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 I h after cadmium. Administration of the chelating agent at later 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.

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Mark M. Jones

Address correspondence to Dr. Mark M. Jones, Box 1583, Station B, Vanderbilt University, Nashville, Tennessee 37235, USA.