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Both sexes of F344 rats were gavaged with maximal tolerated doses of mercuric chloride for periods from 2 wk to up to 2 yr to investigate chronic nephrotoxicity and potential carcinogenicity. The toxicity of mercuric chloride was excessive after 2 wk of exposure to doses ranging from 1.25 to 20 mg/kg, compromising renal function by selectively destroying cells of the proximal tubules, and eliciting marked elevations in urinary biomarker enzymes diagnostic for acute renal tubule necrosis. In the 2-wk studies, urinary alkaline phosphatase and aspartate amino-transferase were most sensitive to renal mercury toxicity among a panel of six enzymes, exhibiting twofold increases above controls at the 5.0 mg/kg dose, before changes in the other enzymes occurred. Urinary lactate dehydrogenase was the most responsive enzyme, with up to 11-fold increases in activity above controls. In response to mercuric chloride exposure of 5.0 mg/kg for 2-6 mo, the greatest and most persistent increases in elevation of urinary enzyme activities were exhibited by alkaline phosphatase and gamma-glutamyl transferase, which increased two-to threefold above controls. At this interval, the maximal severity of the renal lesions in both sexes of rats was graded as minimal to mild. Beyond 6 mo none of the urinary enzymes measured in this study was adequate as biomarkers of nephrotoxicity, although the severity of the renal lesions had progressed. Mercury accumulated in a dose-related fashion primarily in the kidney, and to a lesser extent in the liver. The severity of the renal lesions was increased by continued exposure to mercuric chloride, as tissue concentrations of mercury rose in proportion to dose. Mercuric chloride treatment for 2 yr clearly exacerbated the severity of the spontaneous nephrotoxicity prevalent in aging F344 rats. The excessive mortality that occurred in the male rats was probably due to a combination of these factors. No renal tumors were detected in rats, possibly because the potential for their development was reduced; however, direct tissue contact with mercury induced squamous-cell papillomas of the forestomach in both sexes.

The renal effect of the daily administration of gentamicin to male albino rats (20 mg/kg body weight) for 6 consecutive days on some biochemical systems of the kidney was examined. Urine volume and urinary protein levels were found to be progressively raised following gentamicin. Urinary alkaline phosphatase, acid phosphatase, muramidase and glutamate dehydrogenase (GDH) activities were found to be markedly elevated. Acid phosphatase and GDH activities in urine were raised 24 h and 48 h, respectively, from the onset of gentamicin administration. The sequence in which some regions of the renal cells were involved in gentamicin nephrotoxicity was determined and the probable mechanism of interaction of gentamicin antibiotic with the renal tubular cells is proposed.