Hartmann Clair, Nussbaum Benedikt, Calzia Enrico, Radermacher Peter, Wepler Martin
Institute of Anesthesiological Pathophysiology and Process Engineering, Ulm University HospitalUlm, Germany.
Department of Anesthesiology, Ulm University HospitalUlm, Germany.
Front Physiol. 2017 Sep 19;8:691. doi: 10.3389/fphys.2017.00691. eCollection 2017.
The role of nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (HS) as poisonous gases is well-established. However, they are not only endogenously produced but also, at low concentrations, exert beneficial effects, such as anti-inflammation, and cytoprotection. This knowledge initiated the ongoing debate, as to whether these molecules, also referred to as "gaseous mediators" or "gasotransmitters," could serve as novel therapeutic agents. In this context, it is noteworthy, that all gasotransmitters specifically target the mitochondria, and that this interaction may modulate mitochondrial bioenergetics, thereby subsequently affecting metabolic function. This feature is of crucial interest for the possible induction of "suspended animation." Suspended animation, similar to mammalian hibernation (and/or estivation), refers to an externally induced hypometabolic state, with the intention to preserve organ function in order to survive otherwise life-threatening conditions. This hypometabolic state is usually linked to therapeutic hypothermia, which, however, comes along with adverse effects (e.g., coagulopathy, impaired host defense). Therefore, inducing an on-demand hypometabolic state by directly lowering the energy metabolism would be an attractive alternative. Theoretically, gasotransmitters should reversibly interact and inhibit the mitochondrial respiratory chain during pharmacologically induced suspended animation. However, it has to be kept in mind that this effect also bears the risk of cytotoxicity resulting from the blockade of the mitochondrial respiratory chain. Therefore, this review summarizes the current knowledge of the impact of gasotransmitters on modulating mitochondrial function. Further, we will discuss their role as potential candidates in inducing a suspended animation.
一氧化氮（NO）、一氧化碳（CO）和硫化氢（HS）作为有毒气体的作用已得到充分证实。然而，它们不仅在体内产生，而且在低浓度时还具有有益作用，如抗炎和细胞保护作用。这一认识引发了一场持续的争论，即这些分子，也被称为“气体介质”或“气体递质”，是否可以作为新型治疗药物。在这种背景下，值得注意的是，所有气体递质都特异性地靶向线粒体，并且这种相互作用可能调节线粒体生物能量学，从而随后影响代谢功能。这一特性对于可能诱导“假死状态”至关重要。假死状态类似于哺乳动物的冬眠（和/或夏眠），是指一种外部诱导的低代谢状态，目的是在其他可能危及生命的情况下保护器官功能。这种低代谢状态通常与治疗性低温有关，然而，治疗性低温会带来不良反应（如凝血障碍、宿主防御受损）。因此，通过直接降低能量代谢来诱导按需低代谢状态将是一种有吸引力的替代方法。理论上，在药理学诱导的假死状态期间，气体递质应可逆地相互作用并抑制线粒体呼吸链。然而，必须记住，这种效应也存在因线粒体呼吸链阻断而导致细胞毒性的风险。因此，本综述总结了目前关于气体递质对调节线粒体功能影响的知识。此外，我们将讨论它们作为诱导假死状态潜在候选物的作用。
