A study on cadmium-induced nephropathy in rats pretreated with puromycin aminonucleoside

Nephrotoxicity of cadmium (Cd) was investigated using puromycin aminonucleoside (AN)-pretreated rats. AN pretreatment was performed by iv injection of 100 mg AN/kg body wt 11 days before the initial Cd injection. Since massive proteinuria and focal glomerular deposits were recognized, glomerular permeability is considered to be increased in AN-pretreated rats. AN-pretreated and intact rats were injected sc with 3 mg Cd/kg body wt, 4 times a week. In non-pretreated rats, slight tubular vacuolation was seen after 1-week Cd exposure and severe vacuolation and coagulative necrosis of the tubules was observed after 2-week Cd exposure. On the other hand, AN pretreatment delayed the onset of vacuolation and necrosis for 1 week and made the lesion milder. After 1-week Cd exposure, a larger amount of Cd was excreted into the urine of AN-pretreated rats than of non-pretreated ones, whereas Cd accumulation in the kidney and liver was lower in AN-pretreated rats than in non-pretreated ones. Thereafter, no difference in Cd concentration was recognized between two groups. From these findings, it is suggested that in early stage of Cd administration, Cd was filtered through the glomerular basement membrane modified by AN pretreatment and that this filterable Cd did not have nephrotoxic effects in AN-pretreated rats.