Masek L, Richards R J
Department of Biochemistry, University of Wales College of Cardiff, U.K.
Toxicology. 1990 Sep;63(3):315-26. doi: 10.1016/0300-483x(90)90193-k.
The ability of paraquat to damage mouse lung Clara cells in the presence and absence of herbicide inhibitors is investigated using a cell culture system. Clara cell damage is assessed on the loss of nitroblue tetrazolium reductase activity and the inability to attach and spread on an extracellular matrix. Endogenous amines such as putrescine and spermidine reduce paraquat-induced damage at low concentrations indicating that they compete for the same cell surface receptor as paraquat and thus potentially block the accumulation of the herbicide. The efficacy of 10 microM exogenous putrescine as a protectant is reduced the longer the time before it is added to the cultures. Clara cells contain high levels of NADPH-dependent P-450 reductase which is required to redox cycle the paraquat and generate reactive oxygen radicals. Compounds with antioxidant properties are examined for their ability to reduce the Clara cell damage. Cystamine, the disulphide form of the naturally occurring thiol, cysteamine, and taurine, a metabolite of cystamine, both of which are accumulated in the lung, do not reduce paraquat-induced Clara cell damage. Another antioxidant, alpha-tocopherol is also ineffective but reduced glutathione (GSH), present in high quantities (3.2 mM) in clara cells, could reduce damage to the cultured cells. Cysteine, a precursor of GSH, can also prevent Clara cell damage when the concentration of paraquat is low.
利用细胞培养系统，研究了在有和没有除草剂抑制剂的情况下百草枯损伤小鼠肺克拉拉细胞的能力。通过硝基蓝四氮唑还原酶活性的丧失以及在细胞外基质上附着和铺展能力的丧失来评估克拉拉细胞损伤。内源性胺如腐胺和亚精胺在低浓度时可减少百草枯诱导的损伤，这表明它们与百草枯竞争相同的细胞表面受体，从而可能阻止除草剂的积累。10微摩尔外源性腐胺作为保护剂的效果，会随着其添加到培养物之前时间的延长而降低。克拉拉细胞含有高水平的NADPH依赖性P-450还原酶，该酶是百草枯氧化还原循环并产生活性氧自由基所必需的。研究了具有抗氧化特性的化合物减少克拉拉细胞损伤的能力。胱胺是天然存在的硫醇半胱胺的二硫化物形式，以及胱胺的代谢产物牛磺酸，这两种物质都在肺中积累，但都不能减少百草枯诱导的克拉拉细胞损伤。另一种抗氧化剂α-生育酚也无效，但克拉拉细胞中大量存在（3.2毫摩尔）的还原型谷胱甘肽（GSH）可以减少对培养细胞的损伤。半胱氨酸是GSH的前体，当百草枯浓度较低时，也可以预防克拉拉细胞损伤。
