Protective effect of astaxanthin against La2O3 nanoparticles induced neurotoxicity by activating PI3K/AKT/Nrf-2 signaling in mice. (October 2020)

• Record Type: Journal Article
• Authors: Yuan, Lu; Qu, Yunhua; Li, Qingzhao; An, Tianyang; Chen, Zhenfei; Chen, Yajing; Deng, Xuenan; Bai, Disi
• Is Part Of: Food and chemical toxicology. Volume 144(2020)
• Publication Date: 2020-10
• Subjects: La2O3 nanoparticles -- Astaxanthin -- PI3K/AKT/Nrf-2 signaling -- Oxidative stress -- Neuroinflammation -- Apoptosis; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111582
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Lanthanum oxide nanoparticles (La2 O3 NPs) are used in photoelectric and catalytic applications. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant and anti-inflammatory properties, and the antioxidant activities promote neuroprotection. This study explored the effect of ASX supplementation on La2 O3 NP-induced neurotoxicity in mice and the molecular mechanisms of such protective effects. Amongst our findings, we determined that ASX treatment significantly attenuated La2 O3 NP-induced behavioural abnormalities, histopathological evidence of hippocampal injury and ultrastructural changes in the CA1 region of the hippocampus. ASX treatment also markedly inhibited the production of ROS and activated PI3K/AKT signaling, which facilitated the nuclear translocation of Nrf-2 and reversed the down-regulation of HO-1, NQO1 and GCLM proteins in the hippocampus that were induced by sub-chronic exposure to La2 O3 NPs. Administration of ASX to mice receiving La2 O3 NPs also resulted in decreased expression of iNOS, IL-1β, TNF-α, COX-2, Bax and Caspase-3 and in increased expression of BDNF, NGF and Bcl-2 observed in response to La2 O3 NPs. In conclusion, ASX had a markedly protective effect against the negative sequelae associated with La2 O3 NP-induced neurotoxicity. This may result from the activation of the PI3K/AKT/Nrf-2 signaling and via the inhibition of oxidative stress, neuroinflammation and cellular apoptosis. Highlights: ASX attenuated histopathological and ultrastructural changes in mice hippocampus. ASX alleviated La2 O3 NP-induced oxidative stress in mice brain. ASX activated the PI3K/AKT/Nrf-2 signaling in La2 O3 NP-treated mice. ASX ameliorated La2 O3 NP-induced neuroinflammatory response and apoptosis.