diethyl-maleate and Acute-Kidney-Injury

Mercury renal disposition has been studied following HgCl2 injection (5.0 mg/kg body wt., s.c.) in controls, diethylmaleate and N-acetylcysteine-treated rats. The different treatments were used to generate statistically different degrees of non-protein sulfhydryls concentration in kidneys. Diethylmaleate (4 mmol/kg body wt., i.p.) diminished kidney glutathione levels to 25% and N-acetylcysteine (2 mmol/kg body wt., i.p.) increased kidney non-protein sulfhydryls levels up to 75% compared with new controls. The amount of mercury in the kidneys, the mercury excretion rate in urine and the mercury plasma disappearance curves were calculated during 3 h post HgCl2 injection. BUN was measured in plasma at the same time period to determine the onset of kidney damage. The results indicate a higher HgCl2 renal clearance in N-acetylcysteine-treated rats compared to controls and less renal mercury accumulation. The data agree with diminished renal toxicity. On the other hand, renal mercury accumulation was higher and mercury renal clearance lower in diethylmaleate-treated animals, associated with higher renal toxicity. The results suggest that non-protein sulfhydryl levels (principally glutathione) might determine renal accumulation of mercury as well as its elimination rate and hence might enhance or mitigate the nephrotoxicity induced by the metal.

Topics: Acetylcysteine; Acute Kidney Injury; Animals; Blood Urea Nitrogen; Glutathione; Kidney; Male; Maleates; Mercuric Chloride; Rats; Rats, Wistar

The effect of lowering renal cortical sulfhydryl concentration on development of acute renal failure (ARF) was evaluated in rats receiving HgCl2 (15 mg/kg body weight, im). Within 90 min after HgCL2 injection urine flow rate and fractional excretion of sodium (FENa) were significantly elevated above control levels, and they remained elevated throughout the 3-h experimental period. Urine flow rate and FENa were not significantly elevated above control levels in animals injected with diethyl maleate (3 mmol/kg, ip) 30 min before and 90 min after HgCl2 (DEM/HgCl2). Administration of DEM alone did not alter renal function. Although lower than control levels, concentrations of protein-bound sulfhydryl groups (PBSH) were comparable in HgCl2- and DEM/HgCl2-treated animals. In contrast, concentrations of nonprotein sulfhydryl groups (NPSH) were 62% lower in DEM/HgCl2 animals than in those treated with HgCl2 alone. Similarly, Hg accumulation was 54% lower in DEM/hgCl2-treated animals than in animals treated with HgCl2 alone. These results suggest that NPSH play an important role in Hg uptake and subsequent development of Hg toxicity.

Topics: Acute Kidney Injury; Animals; Drug Interactions; Male; Maleates; Mercuric Chloride; Mercury; Rats; Rats, Inbred Strains; Sulfhydryl Compounds