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Hemin treatment protects neonatal rats from sevoflurane-induced neurotoxicity via the phosphoinositide 3-kinase/Akt pathway.
Life Sci. 2020 Feb 01; 242:117151.LS

Abstract

AIMS

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.

MAIN METHODS

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.

KEY FINDINGS

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.

SIGNIFICANCE

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.

Authors+Show Affiliations

Shengjing Hospital of China Medical University, Shenyang, China.Shengjing Hospital of China Medical University, Shenyang, China.Shengjing Hospital of China Medical University, Shenyang, China.The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.Shengjing Hospital of China Medical University, Shenyang, China.Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: 494565379@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31843526

Citation

Yang, Fan, et al. "Hemin Treatment Protects Neonatal Rats From Sevoflurane-induced Neurotoxicity Via the Phosphoinositide 3-kinase/Akt Pathway." Life Sciences, vol. 242, 2020, p. 117151.
Yang F, Zhang Y, Tang Z, et al. Hemin treatment protects neonatal rats from sevoflurane-induced neurotoxicity via the phosphoinositide 3-kinase/Akt pathway. Life Sci. 2020;242:117151.
Yang, F., Zhang, Y., Tang, Z., Shan, Y., Wu, X., & Liu, H. (2020). Hemin treatment protects neonatal rats from sevoflurane-induced neurotoxicity via the phosphoinositide 3-kinase/Akt pathway. Life Sciences, 242, 117151. https://doi.org/10.1016/j.lfs.2019.117151
Yang F, et al. Hemin Treatment Protects Neonatal Rats From Sevoflurane-induced Neurotoxicity Via the Phosphoinositide 3-kinase/Akt Pathway. Life Sci. 2020 Feb 1;242:117151. PubMed PMID: 31843526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemin treatment protects neonatal rats from sevoflurane-induced neurotoxicity via the phosphoinositide 3-kinase/Akt pathway. AU - Yang,Fan, AU - Zhang,Yongfang, AU - Tang,Zhiyin, AU - Shan,Yangyang, AU - Wu,Xiuying, AU - Liu,Hongtao, Y1 - 2019/12/13/ PY - 2019/10/23/received PY - 2019/11/30/revised PY - 2019/12/08/accepted PY - 2019/12/18/pubmed PY - 2020/2/6/medline PY - 2019/12/18/entrez KW - Hemin KW - Neuroglobin KW - Neurotoxicity KW - Phosphoinositide 3-kinase/Akt KW - Rats, anaesthesia KW - Sevoflurane SP - 117151 EP - 117151 JF - Life sciences JO - Life Sci. VL - 242 N2 - AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31843526/Hemin_treatment_protects_neonatal_rats_from_sevoflurane_induced_neurotoxicity_via_the_phosphoinositide_3_kinase/Akt_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)31079-3 DB - PRIME DP - Unbound Medicine ER -