Effect on the peripheral nervous system of systemically administered dimethylsulfoxide in the rat: a neurophysiological and pathological study.
The issue of dimethylsulfoxide (DMSO) neurotoxicity is an important one, given its wide use in experimental toxicology as a solvent for hydrophobic substances. We examined the effect of the intraperitoneal administration of different DMSO solutions (1.8-7. 2%) on the peripheral nervous system of Wistar rats treated for 10 consecutive days and followed-up for an additional 45 days. DMSO administration induced a dose-dependent reduction in nerve conduction velocity, with complete recovery occurring in the follow-up. No structural changes were found in the sciatic nerve at 1.8% and 3.6% DMSO concentrations, suggesting that the mechanism of action of DMSO involves a functional impairment (i.e. conduction block) similar to that already described for this substance in isolated systems. However, when DMSO was administered at the 7.2% concentration, evident structural changes were observed in the sciatic nerve, with myelin disruption and uncompacted myelin lamelle. The neurophysiological and pathological changes observed in our study are severe enough to merit careful consideration in the course of experimental studies involving DMSO as a solvent for drugs which are under evaluation for their potential neurotoxicity.
Cavaletti
G
G
Clinica Neurologica, Università di Milano Bicocca, Ospedale S. Gerardo, v. Donizetti 106, 20052 Monza, Italy. guido.cavaletti@unimi.it
Oggioni
N
N
Sala
F
F
Pezzoni
G
G
Cavalletti
E
E
Marmiroli
P
P
Petruccioli
M G
MG
Frattola
L
L
Tredici
G
G
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009431:Neural Conduction / Q000187:drug effects; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D012997:Solvents / Q000633:toxicity; D013623:Tail / Q000294:innervation
D012997:Solvents; D004121:Dimethyl Sulfoxide