Glutathione status, glutathione monoisopropyl ester, and cadmium metabolism in mice.
Glutathione monoisopropyl ester (GSHMI) was synthesized for an investigation of its interactions with cadmium (Cd) in mice. When administered ip prior to the injection of lethal doses of Cd given by the ip or sc route, it did not reduce Cd-induced mortality. When given to Cd-bearing mice it did not promote mobilization of Cd from metallothionein-bound stores in liver, kidneys, spleen, testes, pancreas, or brain. When given at a dose of 6.0 mmol/kg 2 hr prior to administration of Cd, GSHMI enhanced Cd accumulation in kidneys, liver, spleen, and testes, and reduced the accumulation of the metal in brain. When 4.0 mmol/kg of the ester were given at various intervals prior to Cd administration, the major actions observed were substantial increases in Cd concentrations ultimately attained in kidneys and liver at most time intervals examined. Reductions of Cd accumulation were found only in liver and pancreas, and only when GSHMI treatment preceded Cd administration by 30 min. Reduction of endogenous GSH levels by administration of L-buthionine-(S,R)-sulfoximine (BSO) led to moderate increases in Cd accumulation in kidneys and pancreas; Cd deposition was reduced in spleen, testes, heart, lungs, and brain. BSO pretreatment led to only slight or no change in liver Cd accumulation. Sephadex G-75 gel filtration chromatography revealed that GSHMI pretreatment led to only a moderate and transient increase in hepatic Cd-metallothionein content when measured 2 hr after Cd administration; when assessed 1 hr and 3 hr post-Cd, elution profiles of extracts from livers of GSHMI-pretreated mice were indistinguishable from control profiles. We conclude that GSHMI is not an effective agent for the control of Cd toxicity.
Gale
G R
GR
Department of Veterans Affairs Medical Center, Charleston, SC 29403.
Smith
A B
AB
Atkins
L M
LM
Jones
M M
MM
Singh
P K
PK
Meredith
M J
MJ
D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D004347:Drug Interactions; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008668:Metallothionein / Q000494:pharmacology; D051379:Mice; D011292:Premedication
D002104:Cadmium; D008668:Metallothionein; C058293:glutathione monoisopropyl ester; D005978:Glutathione