title: Lithium attenuates peripheral neuropathy induced by paclitaxel in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nasir
authors.initials: N
authors.lastname: Pourmohammadi
authors.forename: Houman
authors.initials: H
authors.lastname: Alimoradi
authors.forename: Shahram Ejtemaei
authors.initials: SE
authors.lastname: Mehr
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Hadian
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
authors.forename: Azam
authors.initials: A
authors.lastname: Bakhtiarian
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D004195:Disease Models, Animal; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D017239:Paclitaxel / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018696:Neuroprotective Agents; D018021:Lithium Chloride; D017239:Paclitaxel