title: Neuroprotection by epigallo catechin gallate against bupivacaine anesthesia induced toxicity involves modulation of PI3/Akt/PTEN signalling in N2a and SH-SY5Y cells.
abstract: Bupivacaine, an amide type long-acting local anaesthetic is commonly employed for epidural anesthesia and as well for nerve blockades. However, studies have shown neurotoxicity following local administration of bupivacaine raising concerns over the use of the drug. Compounds that could minimize or inhibit toxic effects of bupivacaine are of high value in operative settings and in pain management. The present study aims to investigate if epigallo catechin gallate (EGCG) could inhibit or prevent bupivacaine toxicity in neuroblastoma cells (N2a and SH-SY5Y). The viability of N2a and SH-SY5Y cells following exposure to EGCG (10-50 µM) were assessed by MTT assay and Annexin V/PI staining. The influence of EGCG on ROS generation was determined. The expression of apoptotic cascade proteins (Caspases-3, -8 and -9, Bcl-xL, Bad, Bax, Bcl-2) and PI3/Akt pathway proteins (Akt, p-Akt, GSK-3β, p-GSK-3β, PTEN) were analyzed by western blotting. EGCG improved the viability of the cells and inhibited apoptosis by potentially decreasing the expression of caspases and pro-apoptotic proteins. Bupivacaine induced ROS generations were reduced on EGCG exposure. EGCG significantly promoted the phosphorylation of Akt and GSK-3β and down-regulated PTEN, thus activating PI3/Akt signalling. EGCG effectively improved the cell viability and inhibited apoptosis of N2a and SH-SY5Y cells via suppression of ROS generation and modulation of PI3K/Akt signalling cascade.
authors.affiliation: Department of Pediatric Surgery, Linyi People's Hospital Linyi 276003, Shandong, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Pediatric Surgery, Linyi People's Hospital Linyi 276003, Shandong, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Linyi People's Hospital Linyi 276003, Shandong, China.
authors.forename: Yu-Zeng
authors.initials: YZ
authors.lastname: Han
keywords: Anesthesia; NF-KB signalling; PI3/Akt/PTEN; apoptosis; bupivacaine; epigallo catechin gallate