Effect of different renal glutathione levels on renal mercury disposition and excretion in the rat.
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.
Girardi
G
G
Facultad de Ciencias, Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, República Argentina.
Elías
M M
MM
D000111:Acetylcysteine / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D001806:Blood Urea Nitrogen; D005978:Glutathione / Q000032:analysis*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008627:Mercuric Chloride / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
D008298:Maleates; D008627:Mercuric Chloride; C014476:diethyl maleate; D005978:Glutathione; D000111:Acetylcysteine