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Propofol Prevents Oxidative Stress by Decreasing the Ischemic Accumulation of Succinate in Focal Cerebral Ischemia–Reperfusion Injury

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Abstract

Oxidative stress caused by mitochondrial dysfunction during reperfusion is a key pathogenic mechanism in cerebral ischemia–reperfusion (IR) injury. Propofol (2,6-diisopropylphenol) has been proven to attenuate mitochondrial dysfunction and reperfusion injury. The current study reveals that propofol decreases oxidative stress injury by preventing succinate accumulation in focal cerebral IR injury. We evaluated whether propofol could attenuate ischemic accumulation of succinate in transient middle cerebral artery occlusion in vivo. By isolating mitochondria from cortical tissue, we also examined the in vitro effects of propofol on succinate dehydrogenase (SDH) activity and various mitochondrial bioenergetic parameters related to oxidative stress injury, such as the production of reactive oxidative species, membrane potential, Ca2+-induced mitochondrial swelling, and morphology via electron microscopy. Propofol significantly decreased the ischemic accumulation of succinate by inhibiting SDH activity and inhibited the oxidation of succinate in mitochondria. Propofol can decrease membrane potential in normal mitochondria but not in ischemic mitochondria. Propofol prevents Ca2+-induced mitochondrial swelling and ultrastructural changes to mitochondria. The protective effect of propofol appears to act, at least in part, by limiting oxidative stress injury by preventing the ischemic accumulation of succinate.

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Funding

This project was supported by a Grant from the Natural Science Foundation of China (No. 81271456).

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  1. Wei Yu and Dapeng Gao have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, The Fourth Affiliated Hospital of the Harbin Medical University, 37 Yiyuan Road, Harbin, 150001, Heilongjiang, China

    Wei Yu, Dapeng Gao, Wen Jin, Siliang Liu & Sihua Qi

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  1. Wei Yu
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  2. Dapeng Gao
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  3. Wen Jin
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Contributions

Study design: SQ, WY. Study conduct: DG, SL. Data analysis: WY, WJ. Writing paper: WY, SQ. Revising paper: all authors.

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Correspondence to Sihua Qi.

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Yu, W., Gao, D., Jin, W. et al. Propofol Prevents Oxidative Stress by Decreasing the Ischemic Accumulation of Succinate in Focal Cerebral Ischemia–Reperfusion Injury. Neurochem Res 43, 420–429 (2018). https://doi.org/10.1007/s11064-017-2437-z

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