CHRONIC ADMINISTRATION OF SURAMIN INDUCES NEUROTOXICITY IN RATS

In the present study, the ability of suramin 18 mg/kg i.p. twice a wee k to induce chronic neurotoxicity in rats was investigated. After 20 w eeks of suramin treatment, morphological analysis of nerve fibers demo nstrated that 57.7+/-3.2% of them presented vesicular disruption of my elin sheaths; their thickness was 0.23+/-0.07 mu m in suramin-treated rats with respect to 0.43+/-0.07 mu m of controls (P<0.05). To investi gate the interaction between suramin and nerve tissue, the binding of the drug to partially purified myelin P-0 protein obtained from sciati c nerves was analysed. The percentage of suramin bound to rat myelin P -0 protein was 94.0+/-9.5%; this value was decreased to 55.0+/-7.6% wh en heparan sulfate was added to the myelin protein suspension before s uramin. The analysis of tissue drug concentrations at 5, 10 and 20 wee ks 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+/-1 5.6 mu g/g of tissue, respectively). In conclusion, suramin induces a chronic peripheral neurotoxicity in rats characterized by myelin damag e and high tissue levels of the drug. The high affinity of suramin for partially purified myelin P-0 protein suggests a possible mechanism f or drug-induced toxicity. (C) 1997 Elsevier Science B.V.