Glutathione monoethyl ester moderates mercuric chloride-induced acute renal failure.
Glutathione (GSH)-dependent reactions are an important cellular defense against ischemic or oxidative injury, although their role in toxin-induced renal cellular injury is less clear. Because of the known sulfhydryl reactivity of mercury (M), we hypothesized that GSH could modify mercuric chloride (MC)-induced acute renal failure (ARF). Therefore, we evaluated the effects of glutathione monoethyl ester (GE), which produces high intrarenal levels of GSH, on the nephrotoxicity of MC. GE treatment in normal rats did not alter their creatinine clearance (CCr), fractional sodium (CNa/CCr) or lysozyme (CLy/CCr) excretion, but histologically resulted in prominent proximal tubular vacuolization. GE pretreatment in rats with MC-induced ARF resulted in partial preservation of their CCr, CNa/CCr and CLy/CCr. Renal histology also demonstrated a reduction in tubular necrosis. M content in the renal cortex 3 following MC was lower in the MC + GE group, but levels were higher in the liver and inner stripe/inner medulla as compared to animals receiving MC alone. No differences were seen in the outer stripe at 3 h or in any of the tissues 24 h following MC injection. Thus, GE moderated MC-induced ARF, likely by providing a large intracellular sulfhydryl pool and thereby reducing M reactivity with endogenous cellular proteins and enzymes.
Houser
M T
MT
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68198-2165.
Milner
L S
LS
Kolbeck
P C
PC
Wei
S H
SH
Stohs
S J
SJ
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008628:Mercury / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains
D008627:Mercuric Chloride; C042431:S-ethyl glutathione; D008628:Mercury; D005978:Glutathione