lithium-chloride and Peripheral-Nervous-System-Diseases

As a cancer chemotherapeutic agent, paclitaxel (Taxol® ) causes dose-related peripheral neuropathy in human beings. The mechanisms underlying this toxicity are currently unknown, and there are no validated treatments for its prevention or control. To assess whether lithium as a pre-treatment and at subtherapeutic dose could prevent the peripheral neuropathy produced by it, rats were treated with paclitaxel (2 mg/kg i.p. every other day for a total of 16 times) and/or lithium chloride (300 mg/l) via water supply. General toxicity and body-weight were measured regularly during the experiment. To evaluate the sensory and motor neuropathy hot-plate, open-field test and nerve conduction velocity were used. In rats treated with only paclitaxel, there was behavioural, electrophysiological and histological evidence of a mixed sensorimotor neuropathy after 16 injections. Lithium robustly reduced the rate of mortality and general toxicity. Paclitaxel-induced sensorimotor neuropathy was significantly improved as indicated by changes in hotplate latency, total distance moved and a significant increase in sciatic, sural and tail sensory or motor nerve conduction velocity. The same results were observed in histopathological examinations; however, dorsal root ganglion neurons did not significantly change in the paclitaxel-treated groups. These results suggest that lithium, at subtherapeutic doses, can prevent both motor and sensory components of paclitaxel neuropathy in rats. Thus, lithium at these doses, as an inexpensive and relatively safe salt, may be useful clinically in preventing the neuropathy induced by paclitaxel treatment.

Topics: Animals; Antineoplastic Agents, Phytogenic; Disease Models, Animal; Lithium Chloride; Male; Motor Neurons; Neural Conduction; Neuroprotective Agents; Paclitaxel; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley

Vincristine (VCR) as a frequently used antimitotic agent which is commonly prescribed for wide spectrum of neoplasm, causes mixed sensorimotor neuropathy. Several evidences show lithium could be a neuroprotective agent, therefore to assess whether a pretreatment and at subtherapeutic dose it could prevent the peripheral neuropathy produced by VCR, rats were treated with VCR 0.1mg/kg i.p. for 3 alternative doses and / or lithium chloride (20mg/kg or 40 mg/kg i.p. daily from the first day to the day of sacrifice). Erythrocyte lithium concentration (ELC) and plasma lithium concentration (PLC) were measured at the seventh day of study and the day of scarification. After seventh day of lithium administration, PLC and ELC reached to a steady state at subtheraputic dose and they did not significantly change at normal housing situation. Hot plate, open field test and nerve conduction velocity were used to evaluate the sensory and motor neuropathy. Only VCR treated rats showed behavioral, electrophysiological and histological evidences of a mixed sensorimotor neuropathy by significant increase in hot plate latencies and a marked decrease in total distance moved and conduction velocities in both sensory and motor nerves. Lithium at the dose of 20mg/kg and specially 40mg/kg robustly reduced the rate of mortality, general toxicity and was able to ameliorate mixed sensorimotor neuropathy induced by VCR. These results suggest that lithium at dose of 20mg/kg and 40 mg/kg, potentially by its effects on cell survival pathways such as inhibition of glycogen synthase kinase-3 (GSK3β), can prevent both motor and sensory components of VCR neuropathy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Lithium Chloride; Male; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Vincristine