New insight in colistin induced neurotoxicity with the mitochondrial dysfunction in mice central nervous tissues.
In the present study, the mechanism of colistin-induced neurotoxicity was investigated with a focus on behavioral characters, mitochondrial ultrastructures and functions of the central nerve tissues in mice followed by administrating intravenously 15 (divided into two dose and 12 h apart), 7.5 and 5 mg/kgbw colistin sulfate for 1, 3 or 7 days successively. To assess the recoverability of colistin-induced neurotoxicity, the neurotoxicity was also examined on day 15 (8 post colistin sulfate administration for 7 days). The results showed that, the spontaneous activities of mice were significantly decreased on days 3 and 7 in the 15 mg/kg group compared with the correspondingly control group. The abnormal ultrastructure changes of mitochondria were presented in their nervous tissues and changed in a dose- and time-dependent manner, e.g. severe vacuolation and fission on days 3 and 7 in the 15 mg/kg group and more slight on day 7 in the 7.5 mg/kg group. In addition, mitochondrial permeability transition (MPT), membrane potential (Δψm) and activities of mitochondrial succinate dehydrogenase changed, showing that colistin affected the mitochondrial functions. The recoverability of colistin-induced neurotoxicity was showed and only slight injury occurred in the nerve tissues of mice on day 15 in the 15 mg/kg group and it had no abnormal changes in the behavioral and neuropathology characters in mice on day 15 in the 7.5 and 5 mg/kg groups. The results suggested that mitochondrial dysfunction might partly account for the mechanism of neurotoxicity induced by colistin sulfate.
College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Xiangfang District, Harbin 150030, PR China.
Chongshan
C
Dai
Jichang
J
Li
Jian
J
Li
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D002490:Central Nervous System / Q000000981:diagnostic imaging / Q000187:drug effects*; D003091:Colistin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000000981:diagnostic imaging / Q000187:drug effects*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014463:Ultrasonography
D000900:Anti-Bacterial Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D003091:Colistin
Behavioral test; Colistin sulfate; Mitochondrial dysfunction; Neurotoxicity