Chronic administration of suramin induces neurotoxicity in rats.
In the present study, the ability of suramin 18 mg/kg i.p. twice a week to induce chronic neurotoxicity in rats was investigated. After 20 weeks of suramin treatment, morphological analysis of nerve fibers demonstrated that 57.7+/-3.2% of them presented vesicular disruption of myelin sheaths; their thickness was 0.23+/-0.07 microm in suramin-treated rats with respect to 0.43+/-0.07 microm of controls (P<0.05). To investigate the interaction between suramin and nerve tissue, the binding of the drug to partially purified myelin P0 protein obtained from sciatic nerves was analysed. The percentage of suramin bound to rat myelin P0 protein was 94.0+/-9.5%; this value was decreased to 55.0+/-7.6% when heparan sulfate was added to the myelin protein suspension before suramin. The analysis of tissue drug concentrations at 5, 10 and 20 weeks of treatment showed that suramin accumulated into the sciatic nerve in a time-dependent fashion (130.8+/-18.1, 219.7+/-17.1 and 449.3+/-15.6 microg/g of tissue, respectively). In conclusion, suramin induces a chronic peripheral neurotoxicity in rats characterized by myelin damage and high tissue levels of the drug. The high affinity of suramin for partially purified myelin P0 protein suggests a possible mechanism for drug-induced toxicity.
Di Paolo
A
A
Superior School of University Studies and Doctoral Research S. Anna, Pisa, Italy.
Danesi
R
R
Innocenti
F
F
Bocci
G
G
Nardini
D
D
Fogli
S
S
Pollina
L
L
Rossi
B
B
Del Tacca
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D005260:Female; D018482:Muscle, Skeletal / Q000294:innervation; D018993:Myelin P0 Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D009498:Neurotoxins; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D013498:Suramin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*
D018993:Myelin P0 Protein; D009498:Neurotoxins; D013498:Suramin