title: Protective effects of lycopene against methylmercury-induced neurotoxicity in cultured rat cerebellar granule neurons.
abstract: Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. Oxidative stress and mitochondrial dysfunction are widely accepted as central pathogenic mechanisms of MeHg-mediated neurotoxicity. Lycopene, a carotenoid compound, is a potent antioxidant with demonstrated neuroprotective properties in several experimental models of oxidative damage. The present study was designed to investigate whether lycopene could provide protective effects against MeHg-induced neurotoxicity in cultured rat cerebellar granule neurons (CGNs). The cultured CGNs were pretreated with different dose of lycopene for 2h, followed by the challenge with 500nM MeHg for 12h. It was found that MeHg exposure caused the loss of cell viability and the LDH release. Furthermore, we demonstrated that MeHg exposure significantly elevated intracellular reactive oxygen species generation and mitochondria-derived superoxide production, caused disruption of mitochondrial membrane potential and opening of mPTP, inhibited mitochondrial complex enzyme activities (complex III and complex IV), reduced ATP generation and decreased mtDNA copy numbers and mtDNA transcript levels. However, each of these oxidative damages was efficiently attenuated by lycopene pretreatment. Collectively, these results suggest that lycopene affords protection against MeHg-induced neurotoxicity in CGNs, and these beneficial effects of lycopene may be attributable to its roles in preventing mitochondrial dysfunction.
authors.affiliation: Center for Health Protection of the Second Artillery Force of PLA, Beijing 100071, PR China. Electronic address: qumingyue2008@126.com.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Qu
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Nan
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Gao
authors.forename: Baoshi
authors.initials: B
authors.lastname: Guo
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D000077276:Lycopene; D008767:Methylmercury Compounds / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004272:DNA, Mitochondrial; D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D002338:Carotenoids; D000077276:Lycopene
keywords: 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazole-carbocyanide iodine; BHT; CCK-8; DCFH-DA; JC-1; Lycopene; MeHg; Methylmercury; Mitochondria; NRFU; Oxidative stress; ROS; Reactive oxygen species; THF; butylated hydroxytoluene; cell counting kit-8; dichlorofluorescein diacetate; mPTP; methylmercury; mitochondrial DNA; mitochondrial permeability transition pore; mtDNA; normalized relative fluorescence units; reactive oxygen species; tetrahydrofuran