An acetyl-L-carnitine switch on mitochondrial dysfunction and rescue in the metabolomics study on aluminum oxide nanoparticles. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Li, Xiaobo; Zhang, Chengcheng; Zhang, Xin; Wang, Shizhi; Meng, Qingtao; Wu, Shenshen; Yang, Hongbao; Xia, Yankai; Chen, Rui
• Is Part Of: Particle and fibre toxicology. Volume 13:Issue 1(2016)
• Page Start: 1
• Page End: 19
• Publication Date: 2015-12
• Subjects: Aluminum oxide nanoparticles -- Mitochondria -- Acetyl-L-carnitine -- Nanotoxicology -- Metabolomics; Particles -- Toxicology -- Periodicals; Fibers -- Toxicology -- Periodicals; 615.9
• DOI: 10.1186/s12989-016-0115-y
• Languages: English
• ISSNs: 1743-8977

Abstract

Abstract Background Due to the wide application of engineered aluminum oxide nanoparticles and increased aluminum containing particulate matter suspending in air, exposure of human to nano-scale aluminum oxide nanoparticles (Al2 O3 NPs) is becoming inevitable. Methods In the present study, RNA microarray coupled with metabolomics analysis were used to uncover mechanisms underlying cellular responses to Al2 O3 NPs and imply the potential rescue. Results We found that Al2 O3 NPs significantly triggered down-regulation of mitochondria-related genes located in complex I, IV and V, which were involved in oxidative phosphorylation and neural degeneration pathways, in human bronchial epithelial (HBE) cells. Subsequent cell- and animal- based assays confirmed that Al2 O3 NPs caused mitochondria-dependent apoptosis and oxidative stress either in vitro or in vivo, which were consistent with the trends of gene regulation. To rescue the Al2 O3 NPs induced mitochondria dysfunction, disruption of small molecular metabolites of HBE were profiled using metabolomics analysis, which facilitates identification of potential antagonizer or supplement against nanoparticle-involved damages. Supplementation of an antioxidant, acetyl-L-carnitine, completely or partially restored the Al2 O3 NPs modulated gene expression levels in mitochondrial complex I, IV and V. It further reduced apoptosis and oxidative damages in both Al2 O3 NPs treated HBE cells and animal lung tissues. Conclusion Thus, our results demonstrate the potential mechanism of respiratory system damages induced by Al2 O3 NPs. Meanwhile, based on the metabolomics profiling, application of acetyl-L-carnitine is suggested to ameliorate mitochondria dysfunction associated with Al2 O3 NPs.