Le C T, Hollaar L, van der Valk E J, van der Laarse A
Department of Cardiology, University Hospital, Leiden, The Netherlands.
Cardiovasc Res. 1992 Feb;26(2):133-42. doi: 10.1093/cvr/26.2.133.
The aim was to find effective protection of myocytes against peroxide induced damage in terms of preservation of contractile activity, protection against lipid peroxidation, and protection against cell death.
The components of the glutathione redox cycle, the production of malondialdehyde, cell contractions, and enzyme release from myocytes were measured in cultured neonatal rat heart cells before and after administration of cumene hydroperoxide, 80 mumol.litre-1. The protective action was tested of (1) glucose (10 mmol.litre-1) which stimulates the production of NADPH; (2) Trolox-C (0.16 mmol.litre-1) which is a water soluble analogue of alpha tocopherol and a scavenger of free radicals; and (3) GSSG (0.6 mmol.litre-1) which increases the intracellular concentrations of GSH and GSSG.
Although the three substances tested were equally effective in reducing the formation of malondialdehyde, exogenous GSSG afforded only slight protection against cumene hydroperoxide induced cell death, whereas glucose and Trolox-C were highly effective protectors. The depressant effect of cumene hydroperoxide on beating frequency was not influenced by preincubation with GSSG, nor by coadministration of glucose, but Trolox-C was able to diminish the negative chronotropic action of cumene hydroperoxide.
Effective protection against cumene hydroperoxide induced lipid peroxidation is not associated per se with effective protection against cumene hydroperoxide induced loss of beating frequency and cell death.
旨在从收缩活性的保存、脂质过氧化的防护以及细胞死亡的防护等方面,找到对心肌细胞过氧化物诱导损伤的有效保护方法。
在给予80微摩尔/升氢过氧化异丙苯前后,对培养的新生大鼠心脏细胞中谷胱甘肽氧化还原循环的成分、丙二醛的产生、细胞收缩以及心肌细胞的酶释放进行测定。测试了以下物质的保护作用:(1)刺激NADPH产生的葡萄糖(10毫摩尔/升);(2)作为α-生育酚的水溶性类似物和自由基清除剂的生育三烯酚-C(0.16毫摩尔/升);以及(3)增加细胞内谷胱甘肽和氧化型谷胱甘肽浓度的氧化型谷胱甘肽(0.6毫摩尔/升)。
尽管所测试的三种物质在减少丙二醛形成方面同样有效,但外源性氧化型谷胱甘肽对氢过氧化异丙苯诱导的细胞死亡仅提供轻微保护,而葡萄糖和生育三烯酚-C是高效的保护剂。氢过氧化异丙苯对搏动频率的抑制作用不受与氧化型谷胱甘肽预孵育的影响,也不受葡萄糖共同给药的影响,但生育三烯酚-C能够减弱氢过氧化异丙苯的负性变时作用。
对氢过氧化异丙苯诱导的脂质过氧化的有效保护本身与对氢过氧化异丙苯诱导的搏动频率丧失和细胞死亡的有效保护无关。