OBJECTIVE: To investigate the toxic actions of colistin sulphate on sciatic-tibial nerves of mice. METHODS: Colistin sulphate 7.5 mg·kg -1 was iv administered to Kunming female mice, twice a day. The mice were divided into colistin sulphate 1, 3, 7 d and 7 d post colistin sulphate groups according the adminstration for 1, 3 and 7 d, respectively. The body mass and gait observations were obtained first, followed by determinations of foot splay and the threshold intensity (TI), maximal intensity (MI), compound action potential duration (CAPD), latency of compound action potential (CAPL), compound action potential amplitude (peak to peak) (CAPA), and nerve conduction velocity (NCV) of sciatic-tibial nerve. Serum creatinine (Cre) and urea nitrogen (BUN) concentrations were determined before the first dose on 2nd day (d 2), d 4, d 8 and d 15 (the day of the first dose as the first day). RESULTS: Compared with normal control group, after colistin sulphate was given for 1 d, Cre showed significant difference (P < 0.05); and for 3 d, BUN and body mass showed significant difference, respectively (P < 0.05); after colistin sulphate was given for 7 d, the gait and the foot splay showed significant difference (both P < 0.05). Compared with normal control group, after colistin sulphate was given for 1, 3 and 7 d, TI increased by 60%, 60% and 192% (P < 0.01), respectively; MI increased by 4%, 13% and 100% (P < 0.05), respectively; CAPD increased by 15.1%, 11.5% and 52.8% (P < 0.05), respectively; CAPL prolonged by 9.0%, 9.0% and 14.6% (P < 0.05), respectively; CAPA decreased 0.92%, 16.2% and 47.6% (P < 0.01), respectively; and NCV decreased by 7.6%, 7.5% and 12.7% (P < 0.05), respectively. After 7 d of stopping administration, the gait and the foot splay had no significant differences, and all electrophysiology indexes showed a recovery tendency and only CAPA was significantly different (P < 0.05). CONCLUTION: Nephrotoxicity is earlier than neurotoxicity on mice treated with colistin sulphate, at the same time, the progressive changes in CAP characteristics of the sciatic-tibial nerves are dependent with the time of colistin sulphate administration and abnormal CAPA has the longest duration time.
|Number of pages||6|
|Journal||Chinese Journal of Pharmacology and Toxicology|
|Publication status||Published - Dec 2012|
- Colistin sulphate
- Sciatic-tibial nerve