Schwartz E, Samuni A, Friedman I, Hempelmann E, Golenser J
Sheba Medical Centre, Tel-Hashomer, Jerusalem.
Inflammation. 1999 Aug;23(4):361-70. doi: 10.1023/a:1020261600498.
Oxidant stress is associated with the generation of reactive oxygen species that are responsible for the damage of a variety of cellular components. The prevention of such biological damage can be achieved by dismutation of superoxide to H2O2 which in turn is removed by catalase and GSH peroxidase. However, redox-active iron released during the development of plasmodia in the erythrocyte can mediate the conversion of H2O2 to hydroxyl radical which is more reactive. The roles of SOD and the nitroxide SOD mimic 4-OH,2,2,6,6,tetramethyl piperidine-N-oxyl (Tempol) were examined in P. falciparum grown in vitro. Both compounds did not prevent the interference with growth inflicted by various inducers of oxidant stress. Moreover, Tempol inhibited parasite growth, in agreement with previous experiments depicting accelerated mortality in SOD overexpressing mouse model of malaria. Probably, effective defense against ROS requires balanced increments in antioxidant enzymes and is not necessarily improved by an increase in the activity of one enzyme.
氧化应激与活性氧的产生有关，活性氧会对多种细胞成分造成损伤。通过将超氧化物歧化为过氧化氢，再由过氧化氢酶和谷胱甘肽过氧化物酶将其清除，可预防此类生物损伤。然而，疟原虫在红细胞内发育过程中释放的具有氧化还原活性的铁，可介导过氧化氢转化为活性更强的羟基自由基。研究了超氧化物歧化酶（SOD）和氮氧化物SOD模拟物4-羟基-2,2,6,6-四甲基哌啶-N-氧化物（Tempol）在体外培养的恶性疟原虫中的作用。这两种化合物均不能阻止各种氧化应激诱导剂对生长的干扰。此外，Tempol抑制寄生虫生长，这与先前描述超氧化物歧化酶过表达疟疾小鼠模型中死亡率加速上升的实验结果一致。或许，对活性氧的有效防御需要抗氧化酶的平衡增加，而不一定通过增加一种酶的活性来改善。
