Jurczuk Maria, Moniuszko-Jakoniuk Janina, Brzóska Malgorzata M
Department of Toxicology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland.
Toxicology. 2006 Feb 15;219(1-3):11-21. doi: 10.1016/j.tox.2005.10.022. Epub 2005 Dec 2.
The involvement of low-molecular thiols, such as reduced glutathione (GSH) and metallothionein (Mt), in the mechanisms of the peroxidative action of lead (Pb) and ethanol (EtOH) in liver and kidney was investigated on rats treated with 500 mg Pb/l (in drinking water) and 5 g EtOH/kg body wt./24h (p.o.), alone and in conjunction with each other for 12 weeks. Beside of GSH and Mt, concentration of total and non-protein SH groups (TSH and NPSH, respectively) in these organs as well as the blood activity of dehydratase of delta-aminolevulinic acid (delta-ALAD) and the urinary concentration of delta-aminolevulinic acid (delta-ALA) were determined. The exposure to Pb and EtOH alone and in conjunction with each other led to a decrease in the blood delta-ALAD activity and an increase in the urinary delta-ALA concentration, and these effects were more markedly advanced at co-exposure. In the liver and kidney of rats treated with Pb and/or EtOH, a decrease in concentrations of GSH and NPSH was noted, compared to control. However, in the Pb+EtOH group, only the liver concentrations of NPSH and GSH were lower also compared to the Pb and EtOH groups. The liver concentration of TSH decreased in the rats exposed to EtOH alone and in conjunction with Pb, whereas the kidney concentration of TSH decreased only at co-exposure to Pb and EtOH. Mt concentration was unchanged except for an increase in the liver in the Pb and Pb+EtOH groups. Two-way analysis of variance (ANOVA/MANOVA) revealed that the changes noted at the co-exposure to Pb and EtOH resulted from an independent action of the two xenobiotics as well as from their interactive action. Negative correlations noted between the liver and kidney concentrations of GSH and/or NPSH and recently reported malondialdehyde (MDA, an indicator of lipid peroxidation) concentration in both organs of those rats indicate the relationship between the content of SH groups and the intensity of the Pb and/or EtOH-induced lipid peroxidation. The results allow for the conclusion that the decrease in the liver and kidney concentrations of GSH and NPSH are involved in the mechanisms of the peroxidative action of Pb and EtOH alone and at co-exposure in these organs.
研究了低分子硫醇，如还原型谷胱甘肽（GSH）和金属硫蛋白（Mt），在铅（Pb）和乙醇（EtOH）对大鼠肝脏和肾脏过氧化作用机制中的参与情况。将大鼠分别以500mg Pb/l（饮用水中）和5g EtOH/kg体重/24小时（口服）单独及联合处理12周。除了GSH和Mt，还测定了这些器官中总巯基和非蛋白巯基（分别为TSH和NPSH）的浓度，以及血液中δ-氨基乙酰丙酸脱水酶（δ-ALAD）的活性和尿中δ-氨基乙酰丙酸（δ-ALA）的浓度。单独及联合暴露于Pb和EtOH导致血液中δ-ALAD活性降低，尿中δ-ALA浓度升高，且这些效应在联合暴露时更为明显。与对照组相比，用Pb和/或EtOH处理的大鼠肝脏和肾脏中，GSH和NPSH的浓度降低。然而，在Pb+EtOH组中，与Pb组和EtOH组相比，仅肝脏中NPSH和GSH的浓度也较低。单独暴露于EtOH以及与Pb联合暴露的大鼠肝脏中TSH浓度降低，而仅在Pb和EtOH联合暴露时肾脏中TSH浓度降低。除了Pb组和Pb+EtOH组肝脏中Mt浓度增加外，Mt浓度未发生变化。双向方差分析（ANOVA/MANOVA）表明，Pb和EtOH联合暴露时所观察到的变化是由两种外源化合物的独立作用以及它们的相互作用导致的。在这些大鼠的肝脏和肾脏中，GSH和/或NPSH浓度与最近报道的丙二醛（MDA，脂质过氧化指标）浓度之间的负相关表明了巯基含量与Pb和/或EtOH诱导的脂质过氧化强度之间的关系。结果表明，肝脏和肾脏中GSH和NPSH浓度的降低参与了Pb和EtOH单独及联合暴露于这些器官时的过氧化作用机制。
