Topiramate alters the erythrocyte osmotic fragility and whole blood viscosity

Objectives: Topiramate (TPM) is an antiepileptic drug with carbonic anhydrase (CA) inhibitory effect. Peripheral paresthesia is a common adverse effect of CA inhibitors like acetazolamide, TPM and zonisamide. CA is a crucial enzyme for erythrocyte physiology and related with cell membrane skeletal proteins. One of the determinants of red cell deformability is the viscoelasticity of cell membrane, which in turn dependent on molecular structure of the membrane. Since the inhibition of CA may alter the erythrocyte deformability, and by doing so it may disturb the microcirculation, we investigated dose dependent effects of topiramate on hemorheological parameters. Methods: Wistar albino rats received TPM (50 – 100 – 200 mg/kg/day, po) or its solvent, distilled water, for 3 weeks. Animals were euthanized by cardiac exsanguination, hematocrit level, erythrocyte osmotic fragility, whole blood and plasma viscosity were determined. Statistical analysis was performed by using Jamovi Software and significance was accepted when P<0.05. Results: 50 mg/kg TPM increased the erythrocyte osmotic fragility (P=0.03). Increased fragility seemed to be reflected on hematocrit levels but difference was not significant. On the other hand, 100 mg/kg TPM decreased whole blood viscosity when compared with control group (cPoise, control:4.5±0.7; 100TPM:3.9±0.3, n=6, P=0.04), while plasma viscosity was not affected significantly. Conclusion: Even though, our results seems to opposing each other, we concluded that TPM alters the hemorheological parameter and probably doing so through more than one mechanisms. To be able to improve treatment outcomes and decrease the side effects those mechanisms needs to be investigated and clarified.
Keywords: Topiramate, Erythrocyte deformability, Plasma viscosity, Blood viscosity, Carbonic anhydrase enzyme