Exogenous carbon monoxide protects against mitochondrial DNA‑induced hippocampal pyroptosis in a model of hemorrhagic shock and resuscitation

Fu,Lan; Zhang,Dong‑Xue; Zhang,Li‑Min; Song,Yan‑Cheng; Liu,Feng‑Hai; Li,Yan; Wang,Xu‑Peng; Zheng,Wei‑Chao; Wang,Xiao‑Dong; Gui,Chun‑Xiao; Kong,Xiang‑Jun; Kang,Li‑Qing

doi:10.3892/ijmm.2020.4493

Exogenous carbon monoxide protects against mitochondrial DNA‑induced hippocampal pyroptosis in a model of hemorrhagic shock and resuscitation

Authors:
- Lan Fu
- Dong‑Xue Zhang
- Li‑Min Zhang
- Yan‑Cheng Song
- Feng‑Hai Liu
- Yan Li
- Xu‑Peng Wang
- Wei‑Chao Zheng
- Xiao‑Dong Wang
- Chun‑Xiao Gui
- Xiang‑Jun Kong
- Li‑Qing Kang
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Affiliations: Graduate School, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Gerontology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Radiodiagnosis, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Central Laboratory, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
Published online on: February 7, 2020 https://doi.org/10.3892/ijmm.2020.4493
Pages: 1176-1186
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Carbon monoxide‑releasing molecule‑3 (CORM‑3), which is an exogenous carbon monoxide (CO) compound, slowly releases CO under physiological conditions; this exerts neuroprotective effects against incomplete ischemia/reperfusion injury. The objective of the present study was to investigate whether the administration of CORM‑3 protects against nucleotide‑binding oligomerization domain‑like receptor pyrin domain‑3 (NLRP3) inflammasome formation and neuronal pyroptosis in the hippocampus following hemorrhagic shock and resuscitation (HSR). To establish this, an HSR model was created. Hemorrhagic shock was induced in adult male Sprague‑Dawley rats under sevoflurane anesthesia by bleeding using a heparinized syringe to maintain a mean arterial pressure of 30±5 mmHg for 60 min. Resuscitation was performed by reperfusion of the blood and, if necessary, administering sterile saline to achieve the baseline arterial pressure. Following resuscitation, CORM‑3 (4 mg/kg) was injected via the femoral vein. Neuronal pyroptosis in the hippocampus, mitochondrial morphology, mitochondrial DNA (mtDNA), brain magnetic resonance imaging, expression levels of NLRP3 and the interaction of pro‑caspase‑1 and apoptosis‑associated speck‑like protein containing a CARD domain (ASC) were examined 12 h after HSR; locomotor activity was assessed 7 days after HSR. Compared with HSR‑treated rats, CORM‑3 administration resulted in a lower level of neuronal pyroptosis in the hippocampus, improved mitochondrial morphology, a lower mtDNA level, steadier levels of metabolites, decreased expression levels of NLRP3 and pro‑caspase‑1 interacting with ASC and enhanced locomotor activity. In conclusion, treatment with CORM‑3 ameliorated impairments of locomotor and exploratory activities in a rat model of HSR. The mechanism may be associated with the inhibition of mitochondrial DNA‑induced pyroptosis via improvements in cell metabolism.

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