Interactions between cadmium, selenium and glutathione peroxidase in rat testis

Abstract

In rats given a minimal damaging dose of 109CdCl 2 (0.011 mmole/kg, s.c.), a visible hemorrhagic response was evident after 48 h when testicular Cd uptake exceeded a level of approx. 150 ng/g. Glutathione peroxidase (GSH-Px) activity was elevated in homogenates of these damaged testes. In rats whose testes were not damaged, the Cd levels were below 150 ng/g and the GSH-Px activity was similar to that of control animals injected with sodium acetate. Rat testis cytosol was found to contain two different GSH-Px activities when assayed with cumene hydroperoxide. These could be separated by gel filtration chromatography. The larger species (GSH-Px A) was eluted in the void volume on Sephadex G-150 and incorporated 75Se from Na 2 75SeO 3 given 4 weeks earlier. The smaller species, of approx. 42 000 molecular weight (MW) (GSH-Px B), did not incorporate 75Se and could be distinguished from GSH-Px A by its insensitivity to cyanide (10 mM). CdCl 2 (1 mM) did not inhibit GSH-Px activity when added in vitro to GSH-Px A or B from testicular cytosol, or to purified GSH-Px isolated from ovine erythrocytes. When 109CdCl 2 was given in vivo to rats injected 4 weeks previously with a tracer dose of Na 2 75SeO 3 or added in vitro to cytosol prepared from similarly labeled rats, Sephadex G-150 chromatography of cytosol showed that most of the 109Cd was eluted in a major peak of 34 000 MW. Little or no 109Cd was found in association with 75Se (major peak 140 000 MW) or GSH-Px activity. When 109CdCl 2 was injected into rats given an equimolar dose of Na 2 75SeO 3 30 min previously, 109Cd uptake in cytosol was increased and both 109Cd and 75Se was shifted into a peak of 110 000 MW. The 109Cd-binding peak of approx. 30 000–34 000 MW was the major Cd-binding fraction in cytosol of 7-week-old rats but was not detectable in 4-week-old rats. Susceptibility of the testes to Cd did not correlate with the presence of this peak, however, since 4-week-old rats were occassionally damaged by CdCl 2.