LIPID-PEROXIDATION - A POSSIBLE MECHANISM OF TRICHLOROETHYLENE-INDUCED NEPHROTOXICITY
LIPID-PEROXIDATION - A POSSIBLE MECHANISM OF TRICHLOROETHYLENE-INDUCED NEPHROTOXICITY
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DOI：
10.1016/0300-483x(89)90180-7
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发表时间：
1989-04-01
期刊：
影响因子：
4.5
通讯作者：
MAYER, D
中科院分区：
文献类型：
--
作者：
COJOCEL, C;BEUTER, W;MAYER, D
本研究的目的是探讨脂质过氧化是否在不同氧浓度下（TCE）三氯乙烯引起的小鼠肾毒性中起作用。雄性NMRI小鼠（25-30 g）以1250-1000 mg/kg的麻油剂量灌胃TCE。为了确定TCE诱导的肾皮质和肝组织中还原性谷胱甘肽（GSH）的消耗，小鼠给予1000 mg/kg TCE，然后在TCE给药后0 ~ 6 h杀死，测量GSH的非蛋白巯基。在另一系列实验中，小鼠分别给予125 ~ 1000 mg/kg TCE，并以1500 mg/kg l -丁硫氨酸-s - r -亚砜胺（BSO）预处理2 h。然后将小鼠暴露于10、15、20或100%的氧气环境中3小时，并通过乙烷的呼出来测量体内脂质过氧化。随后，处死小鼠，测定肝脏和肾脏皮层丙二醛（MDA）的生成。用气相色谱法测定乙烷析出度，测定丙二醛为硫代巴比妥酸反应物质。在进一步的一系列实验中，采用与乙烷和丙二醛测定相同的方法处理小鼠，并测定血液尿素氮（BUN）的变化和对氨基马粪酸有机离子（PAH）的积累。采用片中比（S/M）法测定肾皮质多环芳烃（PAH）累积量。给小鼠1000mg /kg TCE 6小时后，肾皮质的GSH明显减少，约为对照组的60%，而肝脏中没有。TCE给药3小时后，只有在10%氧气环境下，肾皮质MDA含量和乙烷呼出量呈剂量依赖性增加。在相同的实验条件下，肝脏中MDA含量保持不变。在TCE给药前，BSO消耗GSH引起肾皮质MDA含量增加和体内乙烷呼出量增加。在10%氧浓度下，TCE诱导肾皮质切片BUN呈剂量依赖性增加，PAH蓄积呈剂量依赖性减少。因此，本研究结果表明，在缺氧条件下，脂质过氧化作用在TCE肾毒性中起作用。
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 1250-1000 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.