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Hemin treatment protects neonatal rats from sevoflurane-induced neurotoxicity via the phosphoinositide 3-kinase/Akt pathway

Author:
Yang, Fan, Zhang, Yongfang, Tang, Zhiyin, Shan, Yangyang, Wu, Xiuying, Liu, Hongtao
Source:
Life sciences 2020 v.242 pp. 117151
ISSN:
0024-3205
Subject:
Western blotting, anesthesia, antioxidant activity, antioxidant enzymes, apoptosis, biochemical mechanisms, brain, brain damage, breathing, caspase-3, heme oxygenase (biliverdin-producing), memory, neonates, neuroprotective effect, neurotoxicity, oxidative stress, phosphatidylinositol 3-kinase, porphyrins, protein-serine-threonine kinases, scaffolding proteins, sevoflurane, signal transduction, superoxide dismutase
Abstract:
Anaesthesia-related neurotoxicity in the developing brain is a controversial issue that has recently attracted much attention. Hemin plays a protective role in hypoxic and ischemic brain damage; however, its effects on sevoflurane-induced neurotoxicity remain unclear. Our aim was to investigate the mechanisms of sevoflurane neurotoxicity and potential neuroprotective roles of hemin upon sevoflurane exposure.Hippocampi were harvested 18 h after sevoflurane exposure. Haem oxygenase 1 (HMOX1), superoxide dismutase 2 (SOD2), discs large MAGUK scaffold protein 4 (DLG4), phosphorylated Akt, Akt, cleaved caspase 3, and neuroglobin were detected by western blotting. A water maze test was used to assess learning and memory ability in P30 rats.Sevoflurane inhalation increased cleaved caspase 3 levels. Hemin treatment enhanced the antioxidant defence response, protecting rats from oxidative stress injury. Hemin plays its neuroprotective role via phosphoinositide 3-kinase (PI3K)/Akt signalling. A single inhalation of sevoflurane did not affect DLG4 expression, while hemin treatment did. Platform crossing increased in rats treated with hemin as well, which may be related to increased DLG4. Neuroglobin expression was not affected, suggesting that it may act upstream of PI3K/Akt signalling.Our study demonstrates that hemin plays a protective role in anaesthesia-induced neurotoxicity by both inhibiting apoptosis via the PI3K/Akt pathway and increasing the expression of antioxidant enzymes, reducing oxidative damage. The results provide mechanistic insight into the effects of sevoflurane anaesthesia on the developing brain and suggest that hemin could help avoid these effects.
Agid:
6799042