Pyridoxine-induced neuropathy in rats: a sensory neuropathy that responds to 4-methylcatechol.
Sensory neuropathies are frequently associated with diabetes or with antimitotic treatments in humans suffering from cancer, and are in this case the most important limitation to the use of antimitotic drugs. For this reason, there is a need to establish and validate animal models of sensory neuropathies that could be routinely used, together with the already known models, for studying and evaluating the effects of putative neuroprotective compounds. In the present study, we prove by behavioral and electromyographical analyses that (a) it is possible to induce a nonlethal, exclusively sensory, reversible neuropathy by intoxicating rats with large amounts of pyridoxine, using a new schedule of intoxication; (b) 4-methylcatechol, a drug known to induce nerve growth factor synthesis, improves the clinical status of pyridoxine-intoxicated animals, shortens the duration of the disease, and restores the morphological integrity of the sensory fibers. Owing to its mode of installation and its clinical features, we propose that this model be used as an additional model for preclinical studies of neuroprotective drugs.
Callizot
N
N
Société Neurofit SA, Immeuble le Platon, rue Jean Sapidus, F-67400 Illkirch, France. callizot@neurofit.com
Warter
J M
JM
Poindron
P
P
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002396:Catechols / Q000494:pharmacology*; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D009475:Neurons, Afferent / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004856:Postural Balance / Q000187:drug effects; D011736:Pyridoxine / Q000506:poisoning*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016138:Walking
D002396:Catechols; D018696:Neuroprotective Agents; C018599:4-methylcatechol; D011736:Pyridoxine