Assessment of mercuric chloride-induced nephrotoxicity by p-aminohippuric acid uptake and the activity of four gluconeogenic enzymes in rat renal cortex.

p-Aminohippurate (PAH) uptake and the activities of four gluconeogenic enzymes were used in vitro as indicators of nephrotoxicity in rats. The purpose was to compare the relative sensitivities of the gluconeogenic enzymes (pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glucose-6-phosphatase), measured in renal cortical homogenates, and PAH uptake, measured in renal cortical slices, following ip treatment with mercuric chloride (HgCl₂). The morphologic aspects of the nephrotoxicity produced by HgCl₂ were also evaluated. A time study (30 days) following administration of 2 mg/kg of HgCl₂ showed that PAH uptake was more sensitive to HgCl₂ than the activities of the four gluconeogenic enzymes. The greatest inhibitory effect was noted on Day 6 and an increase toward normal was seen from Day 7. A dose-response study undertaken 6 days after HgCl₂ showed that 1 mg/kg caused significant decreases in the activities of fructose-1,6-diphosphatase and pyruvate carboxylase. However, PAH uptake was significantly reduced at 0.5 mg/kg; with this dosage no morphologic renal alterations were observed. PAH uptake was found to be more sensitive for detecting HgCl₂-induced nephrotoxicity than were the activities of the four gluconeogenic enzymes, with fructose-1,6-diphosphatase being the most sensitive of the four enzymes.