title: Naringenin pre-treatment inhibits neuroapoptosis and ameliorates cognitive impairment in rats exposed to isoflurane anesthesia by regulating the PI3/Akt/PTEN signalling pathway and suppressing NF-κB-mediated inflammation.
abstract: The volatile anaesthetic isoflurane is one of the most frequently employed general anaesthetics in neonates, children and adults. Accumulating evidence demonstrated that exposure to anaesthetics is associated with widespread neurodegeneration and cognitive impairment. Thus, the identification and development of compounds capable of preventing or reducing these adverse effects is of great clinical importance. For this purpose, the present study aimed to assess the effects of a flavonoid, naringenin, on isoflurane-induced neuroapoptosis and cognitive impairment. Separate groups of neonatal rat pups were administered naringenin at 25, 50 or 100 mg/kg body weight from postnatal day 1 (P1) to P21. On P7, the pups were exposed to 6 h of isoflurane (0.75%) anaesthesia. Neuroapoptosis was examined using the TUNEL assay. The expression of cleaved caspase-3, the apoptotic pathway proteins (Bad, Bax, Bcl-2 and Bcl-xL), the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway proteins [Akt, phosphorylated (-)Akt, glycogen synthase kinase 3β (GSK‑3β), p‑GSK-3β, phosphatase and tensin homolog (PTEN)] and nuclear factor-κB (NF-κB)‑mediated signalling proteins were determined by western blot analysis. General behaviour, as well as the learning ability and memory of the pups were assessed. Naringenin significantly inhibited isoflurane‑induced neuroapoptosis and markedly decreased the protein expression of caspase-3, Bad, Bax, NF-κB, tumor necrosis factor-α, interleukin (IL)-6 and IL-1β. Furthermore, naringenin increased the expression of Bcl-xL and Bcl-2 and activated the PI3K/Akt pathway. Significant improvements in learning capacity and memory retention were observed following naringenin treatment. Naringenin effectively ameliorated cognitive dysfunction and reduced isoflurane‑induced apoptosis as well as modulating the PI3/Akt/PTEN and NF-κB signalling pathways.
authors: Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Fu-Zhou
authors: FZ
authors: Hua
authors: Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Jun
authors: J
authors: Ying
authors: Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Jing
authors: J
authors: Zhang
authors: Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330039, P.R. China.
authors: Xi-Feng
authors: XF
authors: Wang
authors: Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Yan-Hui
authors: YH
authors: Hu
authors: Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Ying-Ping
authors: YP
authors: Liang
authors: Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Qin
authors: Q
authors: Liu
authors: Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Guo-Hai
authors: GH
authors: Xu
mesh_terms: D000280:Administration, Inhalation; D000758:Anesthesia; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007530:Isoflurane; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D044950:Flavanones; D016328:NF-kappa B; D007530:Isoflurane; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D053148:Caspase 3; C005273:naringenin