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Lithium attenuates peripheral neuropathy induced by paclitaxel in rats

As a cancer chemotherapeutic agent, paclitaxel (Taxol(R) ) 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

Keywords : administration & dosage,Animals,Antineoplastic Agents,Antineoplastic Agents,Phytogenic,chemically induced,Disease Models,Animal,drug effects,Injections,Iran,Lithium Chloride,Male,mortality,Motor Neurons,Neural Conduction,Neurons,Neuroprotective Agents,Paclitaxel,Peripheral Nervous System Diseases,pharmacology,prevention & control,Rats,Rats,Sprague-Dawley,Tail,Time,toxicity,Universities,, Attenuates,Peripheral,Neuropathy,Induced,By, fibromyalgia pain management centers

Date of Publication : 2012 Mar

Authors : Pourmohammadi N;Alimoradi H;Mehr SE;Hassanzadeh G;Hadian MR;Sharifzadeh M;Bakhtiarian A;Dehpour AR;

Organisation : Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Journal of Publication : Basic Clin Pharmacol Toxicol

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21917116

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