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.

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 μm in suramin-treated rats with respect to 0.43±0.07 μm of controls (P<0.05). To investigate the interaction between suramin and nerve tissue, the binding of the drug to partially purified myelin Po 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 μg/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 drag-induced toxicity.

Chronic administration of suramin induces neurotoxicity in rats / A. DI PAOLO, R. Danesi, F. Innocenti, G. Bocci, D. Nardini, S. Fogli, L. Pollina, B. Rossi, M. DEL TACCA. - In: JOURNAL OF THE NEUROLOGICAL SCIENCES. - ISSN 0022-510X. - 152:2(1997), pp. 125-131. [10.1016/S0022-510X(97)00185-8]

Chronic administration of suramin induces neurotoxicity in rats

R. Danesi;
1997

Abstract

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 μm in suramin-treated rats with respect to 0.43±0.07 μm of controls (P<0.05). To investigate the interaction between suramin and nerve tissue, the binding of the drug to partially purified myelin Po 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 μg/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 drag-induced toxicity.
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&lt;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.
Suramin; preclinical model; neurotoxicity
1997
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1120063
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