Vincristine-induced neuropathy in rat: electrophysiological and histological study

Abstract

Peripheral sensory-motor neuropathy is one of the most frequent side effects of vincristine (VCR) administration, which often limits its usefulness in the treatment of a wide range of neoplastic diseases. The purpose of this work is to study VCR neurotoxicity in experimental animals from clinical, electrophysiological, and histological points of view. Sixty-five rats were used as a control group and 31 rats were divided into two groups and given VCR in two different regimens: the fixed-dose group (0.2 mg/kg) and the increasing-dose group (0.1 mg/kg, by an increment of 0.05 mg/kg/week). VCR was given intraperitoneally once weekly for five consecutive weeks. Electrophysiological examinations of the control and both treated groups were performed and included measurements of nerve conduction velocity and action potential (AP) amplitude of sciatic and tail nerves weekly during the period of treatment and 14 weeks after discontinuation of treatment. Histological sections of sciatic nerves were examined after the appearance of early electrophysiological changes, at the end of the 5th, and 19th weeks of the study (14 weeks after discontinuation of treatment). With the progress of the treatment, an increasing number of rats showing signs of neurological deficits were observed. During the first 5 weeks of this study, electrophysiological testing showed a nonsignificant difference in the conduction velocities of sciatic and tail nerves between the control and the treated groups, whereas a significant decrease in the amplitude of the sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) of the tested nerves was recorded. The reduction in the AP amplitude was associated with histological changes characterized by axonal degeneration with relative demyelination. Fourteen weeks after discontinuation of treatment, a significant increment in the SNAP and CMAP amplitudes of both sciatic and tail nerves was noticed. While the CMAP amplitude of the distal segment of the tail showed nonsignificant increment, lesser number of fibers with axonal and/or myelin lesions were found. The clinical, electrophysiological, and histological results suggest that VCR induces peripheral sensorimotor neuropathy of axonal type more prominent in the fixed- than the increasing-dose group. The discontinuation of VCR permitted the improvement of the electrophysiological and histological changes. The rat can be used as an animal model for studying VCR neurotoxicity. However, further studies on larger number of animals are required to evaluate the type of nerve fiber involvement and the site of damage.

Mechanisms of vincristine-induced neurotoxicity: Possible reversal by erythropoietin

“…We observed that the amplitude of the MCAP was significantly decreased, while its duration was significantly prolonged in the VCR group. This suggests that a significant number of sensory and motor fibers are affected by the drug as confirmed by reported histological studies, which showed VCR-induced axonal degeneration as well as disorganization of the axonal microtubule cytoskeleton and increase in the caliber of unmyelinated sensory axons (9,16). On the other hand, no significant change was observed in conduction velocity.…”

“…Inc., Chungcheongnamdo, Korea; 1 mg/mL vial) was injected at a dose of 150 μg/kg, intraperitoneally, three times weekly for five consecutive weeks (8,9); Group III (EPO-treated group 1, EPO1 group), this group of rats was treated with VCR at the same dose and route of administration as in group II and concomitantly received human recombinant EPO (Egyptian International Pharmaceutical Industries Co., 10th of Ramadan City, Egypt; 10,000 IU/mL vial) at a dose of 40 μg/kg, intraperitoneally, three times weekly for five consecutive weeks (7); Group IV (EPO-treated group 2, EPO2 group), this group of rats was subjected to the same treatment protocol as in group III, but the EPO dose was doubled (80 μg/kg).…”

Lithium Attenuates Peripheral Neuropathy Induced by Paclitaxel in Rats

“…After the last behavioural tests, six rats were anaesthetized with pentobarbital sodium (65 mg ⁄ kg). Body temperature was then monitored and maintained within normal limits; then, sensory nerve conduction velocity (SNCV) in the left sural and tail nerve and motor nerve conduction velocity (MNCV) in the left sciatic and tail nerve were recorded as previously described using an isometric force transducer (MLT 1030 ⁄ D; AD Instruments, Power Lab, Oxford, UK) and the same stimulating and recording pin electrodes (pin; AD Instrument) [18].…”

Neurotoxicité périphérique des traitements oncologiques: aspects précliniques et cliniques

“…Vincristine L'existence de cette neuropathie a é té confirmé e chez l'animal par O N C O L O G I E une diminution des vitesses de conduction nerveuses et l'existence d'une dé gé né rescence axonale pure distale ou associé e à une dé myé linisation secondaire [23]. Les deux principaux modè les animaux ont ré vé lé l'existence d'une hyperalgé sie et allodynie mé canique associé es à une hyperalgé sie et allodynie thermique au froid [1,6].…”