ACUTE TOXIC EFFECTS OF PARAQUAT AND DIQUAT ON THE RAT-KIDNEY

The bipyridyls, paraquat and diquat, cause mild renal tubular damage in the rat. A marked diuresis, albuminuria, glucosuria, and an increased plasma urea concentration occurred 6-24 hr after paraquat (680, po, or 108 μmol/kg, sc) and an increased urinary excretion of N-acetyl-β-d-glucosaminidase occurred 6-24 hr after paraquat (680 μmol/kg, po). Diquat (680 μmol/kg, po) produced proteinuria and glucosuria 6-24 hr after dosing. Histological examination of the kidneys showed there was mild hydropic degeneration of the proximal convoluted tubules. Mercuric chloride (HgCl2), a nephrotoxic agent, was used as a positive control in these studies dosed at 7.4 μmol/kg, sc, and produced marked tubular necrosis. Biochemical studies showed that both paraquat and diquat decrease N′-methylnicotinamide (NMN) but not p-aminohippurate (PAH) accumulation by renal cortical slices when added in vitro, suggesting competition for the base transport system. However, no decrease in NMN or PAH accumulation was seen in renal cortical slices from rats treated with paraquat or diquat. Both bipyridyls stimulated pentose phosphate pathway and inhibited fatty acid synthesis when added in vitro to renal cortical slices. However, neither of these parameters were affected in renal cortical slices prepared from rats treated with paraquat or diquat. We conclude that both bipyridyls cause renal tubular damage but this damage is mild compared with that seen after HgCl2. And that biochemical indicators of paraquat damage in the lung are not altered in renal cortical slices from bipyridyl-treated rats. These minimal changes observed using histological and biochemical techniques contrast sharply with the effects these compounds have on renal excretory function. © 1979.