colistin and Nerve-Degeneration

To investigate the neurotoxicity of colistin, female mice received colistin sulfate (7.5 mg/kg/12 h) intravenously for 7 days successively, the behavioral changes, and the neuropathological and electrophysiological characterizations of sciatic nerves were determined prior to administration and at 1, 3, 7 and 15 days thereafter. At 1, 3, and 7 days, the compound action potential durations (CAPDs), compound muscle action potential amplitudes (CAPAs), conduction velocities of sciatic-tibial nerve (NCVs) showed progressively abnormal changes with the time prolonged. Compared to the control, these changes were significant at day 7 (p < 0.01, p < 0.05, p < 0.05, p < 0.01 and p < 0.05, respectively), but at day 15, only CAPAs were significantly different (p < 0.05), other indexes presented a recovery tendency. These functional damages were confirmed by the synchronous ultrastructural observations which expressed axonal degeneration and demyelination in the sciatic nerves. These results indicated that peripheral neurotoxicity occurred in mice treated intravenously with colistin sulfate and the electrophysiological and ultrastructural changes of their sciatic nerves exerted in time-dependent fashion.

Topics: Action Potentials; Animals; Anti-Bacterial Agents; Axons; Behavior, Animal; Colistin; Demyelinating Diseases; Electrophysiology; Female; Injections, Intravenous; Mice; Mice, Inbred Strains; Nerve Degeneration; Neural Conduction; Sciatic Nerve; Time Factors; Toxicity Tests

In addition to the classical microtubule inhibitors (antimitotic agents), transganglionic degenerative atrophy of central terminals of primary sensory neurons can be induced also by means of applying to a peripheral nerve basic polypeptides (Polymyxin B and Colimycin) and two basic derivatives of glutamic acid that do not exert any microtubule inhibition. This effect is independent of other pharmacological effects (histamine liberation, Ca2+ -binding, etc.) of the applied compounds, and probably it is based on a competitive reaction with nerve growth factor.

Topics: Animals; Atrophy; Colistin; Female; Glutamates; Histamine; Male; Nerve Degeneration; Neurons, Afferent; Peptides; Polymyxin B; Rats; Rats, Inbred Strains; Sciatic Nerve; Spinal Cord