Lipid peroxidation: a possible mechanism of trichloroethylene-induced nephrotoxicity.
The purpose of this study was to investigate whether lipid peroxidation plays a role in (TCE) trichloroethylene-induced nephrotoxicity in mice at different oxygen concentrations. Male NMRI mice (25-30 g) were treated i.p. with TCE in a dosage of 125-1000 mg/kg in sesame oil. To determine the TCE-induced depletion of reduced glutathione (GSH) in the kidney cortex and liver tissue, mice were given 1000 mg/kg TCE i.p., then killed between 0 and 6 h after TCE administration and GSH was measured was non-protein sulfhydryls. In another series of experiments, mice were administered 125 to 1000 mg/kg TCE i.p. with or without a 2 h i.p. pretreatment with 1500 mg/kg L-buthionine-S-R-sulfoximine (BSO). Mice were then exposed to a 10, 15, 20 or 100% oxygen atmosphere for 3 h and lipid peroxidation in vivo was measured as exhalation of ethane. Subsequently, mice were killed and malondialdehyde (MDA) generation was measured in the liver and kidney cortex. Ethane evolution was estimated by gas chromatography and MDA was determined as thiobarbituric acid reactive substances. In a further series of experiments mice were treated in the same manner as for ethane and MDA determination and the changes in blood urea nitrogen (BUN) and accumulation of the organic ion p-aminohippurate (PAH) were determined. PAH accumulation by renal cortical slices were measured as the slice to medium (S/M) ratio. Six hours after administration of 1000 mg/kg TCE to mice, GSH was significantly depleted to about 60% of control in the kidney cortex but not in the liver. Three hours after TCE administration, MDA content in the kidney cortex and ethane exhalation increased in a dose-dependent manner only under a 10% oxygen atmosphere. Under the same experimental conditions, MDA content remained unchanged in the liver. BSO depletion of GSH prior TCE administration induced an increase of the MDA content in the kidney cortex and an increase of the ethane exhalation in vivo. At 10% oxygen concentration, TCE induced a dose-dependent increase in BUN and a dose-dependent decrease of PAH accumulation by the renal cortical slices. Thus, the results of the present study suggest that, under hypoxic conditions, lipid peroxidation plays a role in TCE nephrotoxicity.
Cojocel
C
C
Hoechest AG, Frankfurt/Main, F.R.G.
Beuter
W
W
Müller
W
W
Mayer
D
D
D000818:Animals; D001806:Blood Urea Nitrogen; D001944:Breath Tests; D019328:Buthionine Sulfoximine; D004980:Ethane / Q000032:analysis; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D010100:Oxygen / Q000494:pharmacology; D014241:Trichloroethylene / Q000633:toxicity*; D010130:p-Aminohippuric Acid / Q000032:analysis
D005609:Free Radicals; D008054:Lipid Peroxides; D008717:Methionine Sulfoximine; D014241:Trichloroethylene; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D005978:Glutathione; D004980:Ethane; D010100:Oxygen; D010130:p-Aminohippuric Acid