title: Curcumin Attenuates Colistin-Induced Neurotoxicity in N2a Cells via Anti-inflammatory Activity, Suppression of Oxidative Stress, and Apoptosis.
abstract: Neurotoxicity is an unwanted side-effect seen in patients receiving therapy with the "last-line" polymyxin antibiotics. This is the first study to show that colistin-induced neurotoxicity in neuroblastoma-2a (N2a) cells gives rise to an inflammatory response involving the IL-1β/p-IκB-α/NF-κB pathway. Pretreatment with curcumin at 5, 10, and 20 μM for 2 h prior to colistin (200 μM) exposure for 24 h, produced an anti-inflammatory effect by significantly down-regulating the expression of the pro-inflammatory mediators cyclooxygenase-2 (COX-2), phosphorylation of the inhibitor of nuclear factor-kappa B (NF-κB) (p-IκB)-α, and concomitantly NF-κB levels. Moreover, curcumin significantly decreased intracellular reactive oxygen species (ROS) production and increased the activities of the anti-ROS enzymes superoxide dismutase, catalase, and the intracellular levels of glutathione. Curcumin pretreatment also protected the cells from colistin-induced mitochondrial dysfunction, caspase activation, and subsequent apoptosis. Overall, our findings demonstrate for the first time, a potential role for curcumin for treating polymyxin-induced neurotoxicity through the modulation of NF-κB signaling and its potent anti-oxidative and anti-apoptotic effects.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, People's Republic of China.
authors.forename: Chongshan
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Pathology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Giuseppe D
authors.initials: GD
authors.lastname: Ciccotosto
authors.affiliation: Department of Pathology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, People's Republic of China.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, People's Republic of China.
authors.forename: Daowen
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, People's Republic of China.
authors.forename: Sanlei
authors.initials: S
authors.lastname: Xie
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, People's Republic of China. xiaoxl@cau.edu.cn.
authors.forename: Xilong
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia. Tony.Velkov@monash.edu.
authors.forename: Tony
authors.initials: T
authors.lastname: Velkov
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003091:Colistin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003474:Curcumin / Q000494:pharmacology*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003474:Curcumin; D003091:Colistin
keywords: Colistin; Curcumin; Inflammation; Mitochondrial dysfunction; Neurotoxicity; Oxidative stress