title: Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane‑induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways.
abstract: Millions of infants and children are exposed to anesthesia every year during medical care. Sevoflurane is a volatile anesthetic that is frequently used for pediatric anesthesia. However, previous reports have suggested that the administration of sevoflurane promotes neurodegeneration, raising concerns regarding the safety of its usage. The present study aimed to investigate caffeic acid phenethyl ester (CAPE) and its protective effect against sevoflurane‑induced neurotoxicity in neonatal rats. Rat pups were administered with CAPE at 10, 20 or 40 mg/kg body weight from postnatal day 1 (P1) to P15. The P7 rats were exposed to sevoflurane (2.9%) for 6 h. Control group rats received no sevoflurane or CAPE. Neuronal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. The expression levels of caspases (caspase‑3, ‑8 and ‑9), apoptotic pathway proteins [Bcl‑2‑associated X protein (Bax), B cell CCL/lymphoma 2 (Bcl‑2), Bcl‑2‑like 1 (Bcl‑xL), Bcl‑2‑associated agonist of cell death (Bad) and phosphorylated (p)‑Bad], mitogen‑activated protein kinases (MAPK) signaling pathway proteins [c‑Jun N‑terminal kinase (JNK), p‑JNK, extracellular signal‑regulated kinase (ERK)1/2, p‑ERK1/2, p38, p‑p38 and p‑c‑Jun] and the phosphoinositide 3‑kinase (PI3K)/Akt cascade were evaluated by western blotting following sevoflurane and CAPE treatment. In addition, the expression of cleaved caspase‑3 was analyzed by immunohistochemistry. CAPE significantly reduced sevoflurane‑induced apoptosis, downregulated the expression levels of caspases and pro‑apoptotic proteins (Bax and Bad) and elevated the expression levels of Bcl‑2 and Bcl‑xL when compared with sevoflurane treatment. Furthermore, CAPE appeared to modify the expression levels of MAPKs and activate the PI3K/Akt signaling pathway. Thus, the present study demonstrated that CAPE effectively inhibited sevoflurane‑induced neuroapoptosis by modulating the expression and phosphorylation of apoptotic pathway proteins and MAPKs, and by regulating the PI3K/Akt pathway.
authors: Department of Pediatric Surgery, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors: Li-Yan
authors: LY
authors: Wang
authors: Department of Orthopedics in Repair and Reconstruction, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors: Zhi-Jun
authors: ZJ
authors: Tang
authors: Department of Pediatric Internal Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors: Yu-Zeng
authors: YZ
authors: Han
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D002109:Caffeic Acids / Q000627:therapeutic use*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008738:Methyl Ethers / Q000009:adverse effects*; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D002109:Caffeic Acids; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D000077149:Sevoflurane; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol