Protection against mercuric chloride by nephrotoxic agents which do not induce thionein

Kidney damage caused by the ip administration of 1.1 mg/kg mercury given as HgCl₂ was less marked in 7-week-old male rats when mercury was given 7 days after the administration of one of the following nephrotoxic agents: 20 mg/kg sodium chromate, 100 mg/kg p-aminophenol, or 500 mg/kg sodium maleate, or 14 days after the injection of 4.0 mg/kg uranyl acetate. All four nephrotoxic agents were given in sufficient doses to cause renal damage. In the first 3–4 days after the administration of the nephrotoxic agents they increased the urinary excretion of alkaline phosphatase, glutamic oxaloacetic transaminase, and lactic dehydrogenase and caused widespread necrosis in the proximal tubular cells. In the first 24 hr after the injection of mercury, the urinary excretion of the three enzymes tested was lower in pretreated than in nonpretreated rats. Tubular cell necrosis was also less extensive in pretreated than in nonpretreated rats, and calcification could be seen 10 days after mercury only in the kidneys of the nonpretreated rats. The decreased susceptibility of regenerating kidneys to the tubulotoxic effect of mercuric chloride seems to be a general phenomenon which is unrelated to the renal concentration of metallothionein or change in renal mercury uptake.