title: Ascorbic acid protects against colistin sulfate-induced neurotoxicity in PC12 cells.
abstract: This study aimed to examine the protective effect of ascorbic acid against colistin-induced neurotoxicity mediated by oxidative stress, a potential mechanism. An in vitro neurotoxicity model was established with PC12 cells exposed to 125 µg/mL colistin sulfate for 24 h. PC12 cells were treated with colistin (125 µg/mL) in the absence and presence of ascorbic acid (0.1, 1.0 and 10 µM/mL) for 24 h. Both 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were carried out to evaluate cell viability. The levels of intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione (GSH) levels were assessed. Moreover, we tested the level of DNA fragmentation, the release of cytochrome-c and the expressions of caspase-9 and -3 mRNA. The results showed that 1 and 10 µM/mL ascorbic acid significantly increased the cell viability and the levels of SOD and GSH (both p<0.05), while 0.1, 1 and 10 µM/mL ascorbic acid significantly decreased the generation of ROS, the release of cytochrome-c, formation of DNA fragmentation and the expressions of caspase-9 and -3 mRNA in colistin-treated PC12 cells, compared with the colistin model group. These results suggest that ascorbic acid could reduce colistin sulfate-induced neurotoxicity through the resistance of oxidative stress and the prevention of apoptosis mediated via mitochondria pathway. They also highlight the potential of coadministering ascorbic acid to widen the therapeutic dose of colistin.
authors.affiliation: College of Veterinary Medicine and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Chongshan
authors.initials: C
authors.lastname: Dai
authors.forename: Ruixia
authors.initials: R
authors.lastname: Gao
authors.forename: Jichang
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001483:Base Sequence; D053148:Caspase 3 / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics; D003091:Colistin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D045304:Cytochromes c / Q000378:metabolism; D017931:DNA Primers; D005978:Glutathione / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D013482:Superoxide Dismutase; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione; D001205:Ascorbic Acid; D003091:Colistin