Salet C, Moreno G, Bazin M, Santus R
Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Aug;50(2):295-303. doi: 10.1080/09553008614550671.
A first attempt to impair a biological function by the synergistic effects of HpD and nitroimidazoles (metronidazole or misonidazole) under anaerobic conditions is reported. A function tightly linked to a membrane has been chosen as model and the Ca2+ movements through the inner mitochondrial membrane have been studied. When isolated mitochondria (1 mg/cm3) are irradiated in oxic condition with 25 micrograms/cm3 HpD and 1 mmol dm-3 nitroimidazole in the medium, Ca2+ uptake is stopped after 15 s of irradiation. When irradiated in anoxic conditions with 25 micrograms/cm3 HpD alone, addition of ATP triggers a normal Ca2+ uptake even after 10 min of irradiation. In contrast Ca2+ uptake is stopped by 1 min irradiation after addition of 1 mmol dm-3 misonidazole to HpD and by 2 min irradiation after addition of 1 mmol dm-3 metronidazole. Thus, under these experimental conditions, the enhancement ratio of the HpD action (defined as the ratio of the durations of irradiation necessary to obtain the cessation of Ca2+ uptake before and after addition of a component other than HpD) is of the order of 40, 10 and 5 for oxygen, misonidazole and metronidazole, respectively. Misonidazole is still efficient at a concentration of 0.1 mmol dm-3.
据报道，首次尝试在厌氧条件下通过血卟啉衍生物（HpD）与硝基咪唑类药物（甲硝唑或米索硝唑）的协同作用来损害生物功能。已选择一种与膜紧密相关的功能作为模型，并研究了钙离子通过线粒体内膜的移动情况。当分离的线粒体（1毫克/立方厘米）在有氧条件下用25微克/立方厘米的HpD和1毫摩尔/立方分米的硝基咪唑在培养基中照射时，照射15秒后钙离子摄取停止。当在无氧条件下仅用25微克/立方厘米的HpD照射时，即使照射10分钟后添加ATP仍能触发正常的钙离子摄取。相比之下，在HpD中添加1毫摩尔/立方分米的米索硝唑后，照射1分钟可使钙离子摄取停止；添加1毫摩尔/立方分米的甲硝唑后，照射2分钟可使钙离子摄取停止。因此，在这些实验条件下，HpD作用的增强比率（定义为在添加除HpD之外的成分之前和之后获得钙离子摄取停止所需的照射持续时间之比）对于氧气、米索硝唑和甲硝唑分别约为40、10和5。米索硝唑在浓度为0.1毫摩尔/立方分米时仍然有效。
