Inhibition of lipid peroxidation without prevention of cellular injury in isolated rat hepatocytes.
Inhibition of lipid peroxidation without prevention of cellular injury in isolated rat hepatocytes.
复制标题
抑制脂质过氧化而不预防离体大鼠肝细胞的细胞损伤。
DOI：
10.1016/0041-008x(81)90110-1
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发表时间：
1981
影响因子：
3.8
通讯作者：
Klaassen,CD
中科院分区：
文献类型：
--
作者：
Stacey,NH;Klaassen,CD
脂质过氧化在组织损伤中的作用一直是许多研究的主题。最近有证据表明，各种化学物质引起的脂质过氧化是肝细胞活力丧失的直接原因。在本研究中，用胶原酶灌流技术分离的肝细胞在Tris缓冲液中孵育，或在含有和不含有抗氧化剂N，N‘-二苯基-对苯二胺(2.5μm)的培养液中孵育。为了确定脂质过氧化与细胞损伤之间是否存在关系，在6小时的孵育期内采集样本，以估计硫代巴比妥酸(TBA)反应物、脂质的二烯结合物的浓度以及细胞内钾离子(K+)和天冬氨酸氨基转移酶(AST)的损失。同时测定还原型谷胱甘肽(GSH)含量。同样的参数也在细胞中进行了研究，悬浮在199的培养液中，分别与碘乙酰胺钠(100μm)、马来酸二乙酯(4 MM)或钒酸钠(400μm)孵育。还研究了DPPD(2.5μm)对这些化学物质诱导的反应的影响。在细胞存活率、细胞内K+和AST漏出量方面，199是一种较好的孵育缓冲液。此外，当使用199培养液而不是Tris时，GSH保持在更高的浓度，并且没有发现较少的脂质过氧化证据。但在DPPD存在下，TBA反应物浓度的升高受到抑制，而DPPD对K+和AST的释放及GSH浓度的降低无保护作用。三种化学处理，即碘乙酰胺钠、马来酸二乙酯和钒酸钠，都会导致细胞活力丧失，GSH显著和迅速下降，并增加脂质过氧化的估计。DPPD可完全抑制碘乙酰胺所致的脂质过氧化，但仅延缓和不阻止K+的丢失，对GSH的丢失无影响。同样，DPPD可抑制顺丁烯二酸二乙酯所致的脂质过氧化，但对细胞存活率的下降或谷胱甘肽的丧失无明显影响。DPPD可阻止钒引起的细胞活力下降，但在孵育6小时时，DPPD与钒共同孵育的肝细胞内K+显著低于单独DPPD孵育的肝细胞。同样，DPPD抑制了脂质过氧化的增加，但不能改变钒处理后GSH的损失。总体而言，这项研究的结果表明，脂质过氧化并不是与在不同介质中孵育或对碘乙酰胺和马来酸二乙酯等化学物质的反应有关的细胞活力丧失的完全原因。
The role of lipid peroxidation in tissue injury has been the subject of many investigations. Recently evidence has suggested that lipid peroxidation due to various chemicals is directly responsible for loss of hepatocyte viability. In the present study hepatocytes, isolated by a collagenase perfusion technique, were incubated in either a Tris buffer or Medium 199 with and without the antioxidant N,N′-diphenyl-p-phenylenediamine (DPPD) (2.5 μm). In order to determine if there is a relationship between lipid peroxidation and cell injury, samples were taken over a 6-hr incubation period for estimation of concentration of thiobarbituric acid (TBA) reactants, diene conjugates of lipids, and loss of intracellular potassium ion (K+) and aspartate aminotransferase (AST). The content of reduced glutathione (GSH) was also assessed. The same parameters were also investigated in cells, which were suspended in Medium 199, incubated with either sodium iodoacetamide (100 μm), diethyl maleate (4 mm), or sodium vanadate (400 μm). The effects of DPPD (2.5 μm) on the responses induced by these chemicals were also studied. Medium 199 was found to be a superior incubation buffer with respect to the cellular viability characteristics, leakage of intracellular K+and AST. Furthermore, GSH was maintained at much higher concentrations and there was less evidence of lipid peroxidation when Medium 199 was used rather than Tris. However, in the presence of DPPD the increase in concentration of TBA reactants was inhibited but DPPD had no protective effect on the release of K+and AST or the decrease in GSH concentration. The three chemical treatments, sodium iodoacetamide, diethyl maleate, and sodium vanadate, each caused loss of cell viability, marked and rapid decrease in GSH, and increases in the estimates of lipid peroxidation. DPPD completely inhibited the lipid peroxidation due to sodium iodoacetamide, but only delayed and did not prevent the loss of K+and had no effect on the loss of GSH. Similarly, DPPD inhibited the lipid peroxidation due to diethyl maleate but did not cause a significant change in the decline of cell viability or alteration in the loss of GSH. The decrease in cell viability produced by vanadium was prevented by DPPD, although at 6 hr of incubation intracellular K+was significantly lower in hepatocytes incubated with DPPD plus vanadium than those with DPPD alone. Again DPPD inhibited the increase in lipid peroxidation but did not alter the loss of GSH with vanadium treatment. Overall the results of this study suggest that lipid peroxidation is not totally responsible for the loss of cellular viability associated with incubation in different mediums or in response to chemicals such as sodium iodoacetamide and diethyl maleate.
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影响因子：
3.6
作者：
G. Poli;E. Gravela;E. Albano;M. Dianzani
通讯作者：
M. Dianzani
比较金属对离体大鼠肝细胞细胞损伤和脂质过氧化的影响。
DOI：
10.1080/15287398109529965
发表时间：
1981
期刊：
Journal of toxicology and environmental health
影响因子：
--
作者：
Stacey,NH;Klaassen,CD
通讯作者：
Klaassen,CD
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影响因子：
3.9
作者：
G. Poli;M. Chiono;T. Slater;M. Dianzani;E. Gravela
通讯作者：
E. Gravela
离体大鼠肝细胞中的脂质过氧化：与 CCl4、ADP/Fe3 和马来酸二乙酯毒性的关系。
影响因子：
3.8
作者：
N. Stacey;B. Priestly
通讯作者：
B. Priestly
苯巴比妥和马来酸二乙酯对离体大鼠肝细胞四氯化碳毒性的影响。
影响因子：
3.6
作者：
T. Lindstrom;M. W. Anders;H. Remmer
通讯作者：
H. Remmer