Brazilian Journal of Anesthesiology (Mar 2023)

The antioxidant effect of preischemic dexmedetomidine in a rat model: increased expression of Nrf2/HO-1 via the PKC pathway

  • Yong-Hee Park,
  • Hee-Pyoung Park,
  • Eugene Kim,
  • Hannah Lee,
  • Jung-Won Hwang,
  • Young-Tae Jeon,
  • Young-Jin Lim

Journal volume & issue
Vol. 73, no. 2
pp. 177 – 185

Abstract

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Background: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. Methods: Thirty-eight rats were randomly assigned to five groups: sham (n...=...6), ischemic (n...=...8), chelerythrine (a PKC inhibitor; 5...mg.kg-1 IV administered 30...min before cerebral ischemia) (n...=...8), dexmedetomidine (100.....g.kg-1 IP administered 30...min before cerebral ischemia (n...=...8), and dexmedetomidine...+...chelerythrine (n...=...8). Global transient cerebral ischemia (10...min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24...hours after ischemia insult. Results: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p...<...0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p...<...0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p...<...0.05 and p...<...0.01, respectively) and diminished its beneficial neuroprotective effects. Conclusion: Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

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