Strategies for therapeutic hypometabothermia

Liu, Shimin; Chen, Jiang‐Fan

doi:10.6030/1939-067x-5.1.31

Cited by 10 publications

(2 citation statements)

References 135 publications

(143 reference statements)

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“…H 2 S is a gaseous mediator that may be a promising therapy for preserving organ function and life during suspended animation in vivo models [ 43 ]. Major targets clearly include the inhibition of mitochondrial cytochrome c oxidase and activation of endothelial cell K + -ATPase channels, but the downstream effects of both pathways are highly context-dependent.…”

Section: Discussionmentioning

confidence: 99%

In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats

Wang

Zhang

et al. 2014

BMC Anesthesiol

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BackgroundAcute lung injury (ALI) is a serious disease with high incidence in ICU, and impaired mitochondria function plays a significant role in ALI. In this study, we examined the possible roles of exogenous hydrogen sulfide (H2S) in lung mitochondria regulation in ALI rats.MethodsThe rat ALI model was induced by an intra-tongue vein Lipopolysaccharide (LPS) injection. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly divided 40 Sprague–Dawley rats into five groups: control, LPS injury, LPS + low-dose NaHS (0.78 mg•kg-1), LPS + middle-dose NaHS (1.56 mg•kg-1), and LPS + high-dose NaHS (3.12 mg•kg-1). Rats were killed 3 h after NaHS administration. We calculated a semi-quantitative histological index of lung injury assessments and measured the lung wet-to-dry weight ratio. We further analyzed serum for interleukin-1β levels using enzyme-linked immunosorbent assays. We observed lung mitochondria ultrastructures with an electron microscope. We examined oxidative stress markers in lung mitochondria and the mitochondrial swelling and activity. We analyzed lung mitochondria and cytosol Cyt-c protein expression using Western blotting.ResultsCompared to the control group, the quantitative assessment score index, wet-to-dry weight ratios, and interleukin-1β content in the LPS injury group were significantly increased and the mitochondrial ultrastructure damaged. Furthermore, mitochondrial activity, adenosine triphosphatease, superoxide dismutase, glutathione peroxidase, and mitochondrial Cyt-c protein expression were significantly decreased, and malondialdehyde content, mitochondrial swelling, and cytosol Cyt-c protein expression were significantly increased in the LPS injury group compared to the control group. These effects were lessened by NaHS.ConclusionExogenous H2S provided a protective effect against ALI by decreasing the mitochondrial lipid peroxidation level and protecting the cell structure in the LPS-induced rat models. Its regulatory effect on lung mitochondria is positively correlated with the dosage.

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Section: Discussionmentioning

confidence: 99%

In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats

Wang

Zhang

et al. 2014

BMC Anesthesiol

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“…The most common and classical method of hypothermia induction is systemic cooling, including whole-body surface cooling and endovascular cooling 27 , with surface cooling being relatively simpler, less invasive, and more cost effective. However, surface cooling has been limited in clinical practice due to the slow onset of hypothermia, poor control of core temperatures and several side effects 28 . These led to an increasing interest in studying mild hypothermia (~34 °C) to widen its practicality.…”

Section: Discussionmentioning

confidence: 99%

Phenothiazines Enhance Mild Hypothermia-induced Neuroprotection via PI3K/Akt Regulation in Experimental Stroke

Duan

et al. 2017

Sci Rep

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Physical hypothermia has long been considered a promising neuroprotective treatment of ischemic stroke, but the treatment’s various complications along with the impractical duration and depth of therapy significantly narrow its clinical scope. In the present study, the model of reversible right middle cerebral artery occlusion (MCAO) for 2 h was used. We combined hypothermia (33–35 °C for 1 h) with phenothiazine neuroleptics (chlorpromazine & promethazine) as additive neuroprotectants, with the aim of augmenting its efficacy while only using mild temperatures. We also investigated its therapeutic effects on the Phosphatidylinositol 3 kinase/Protein kinase B (PI3K/Akt) apoptotic pathway. The combination treatment achieved reduction in ischemic rat temperatures in the rectum, cortex and striatum significantly (P < 0.01) faster than hypothermia alone, accompanied by more obvious (P < 0.01) reduction of brain infarct volume and neurological deficits. The combination treatment remarkably (P < 0.05) increased expression of p-Akt and anti-apoptotic proteins (Bcl-2 and Bcl-xL), while reduced expression of pro-apoptotic proteins (AIF and Bax). Finally, the treatment’s neuroprotective effects were blocked by a p-Akt inhibitor. By combining hypothermia with phenothiazines, we significantly enhanced the neuroprotective effects of mild hypothermia. This study also sheds light on the possible molecular mechanism for these effects which involves the PI3K/Akt signaling and apoptotic pathway.

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Antipsychotic inductors of brain hypothermia and torpor-like states: perspectives of application

et al. 2016

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Hypothermia and hypometabolism (hypometabothermia) normally observed during natural hibernation and torpor, allow animals to protect their body and brain against the damaging effects of adverse environment. A similar state of hypothermia can be achieved under artificial conditions through physical cooling or pharmacological effects directed at suppression of metabolism and the processes of thermoregulation. In these conditions called torpor-like states, the mammalian ability to recover from stroke, heart attack, and traumatic injuries greatly increases. Therefore, the development of therapeutic methods for different pathologies is a matter of great concern. With the discovery of the antipsychotic drug chlorpromazine in the 1950s of the last century, the first attempts to create a pharmacologically induced state of hibernation for therapeutic purposes were made. That was the beginning of numerous studies in animals and the broad use of therapeutic hypothermia in medicine. Over the last years, many new agents have been discovered which were capable of lowering the body temperature and inhibiting the metabolism. The psychotropic agents occupy a significant place among them, which, in our opinion, is not sufficiently recognized in the contemporary literature. In this review, we summarized the latest achievements related to the ability of modern antipsychotics to target specific receptors in the brain, responsible for the initiation of hypometabothermia.

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Strategies for therapeutic hypometabothermia

Cited by 10 publications

References 135 publications

In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats

In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats

Phenothiazines Enhance Mild Hypothermia-induced Neuroprotection via PI3K/Akt Regulation in Experimental Stroke

Antipsychotic inductors of brain hypothermia and torpor-like states: perspectives of application

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