GLUTATHIONE EFFECTS ON TOXICITY AND UPTAKE OF MERCURIC-CHLORIDE AND SODIUM ARSENITE IN RABBIT RENAL CORTICAL SLICES

The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl 2 and NaAsO2 is not clear. The metals are known to react with endogeno us sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 10(-4) M HgCl2 or 10(-3) NaAsO2 +/- stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10(-4) M Hg(SG)(2) or 10(-3) M As(SG)( 3)]. Incubations were performed at 37 degrees C in DME-F12 buffer (95/ 5 O-2/CO2) for 8 hr. Hg(SG)(2) reduced slice K+/DNA content, as an ind icator of viability, significantly less than HgCl2. As(SG)(3) exhibite d a 2-hr delay in K+/DNA content reduction compared to NaAsO2. This de lay in toxicity was not correlated to changes in uptake. Arsenic and m ercury accumulation, determined by proton-induced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCl2 cytotoxicity and was correlated to a dec rease in Hg accumulation in the slice. Exogenous GSH had limited ii an y protective effects against cytotoxicity by NaAsO2 and a decrease in As accumulation was not observed. Complex metal-GSH interactions appea r to exist and impact on the uptake and toxicity of these metals.