Late vascular effects of topiramate treatment in Wistar rats during childhood

Late vascular effects of topiramate treatment in Wistar rats during childhood

• Autor
• Camila Borecki Vidigal
• Co-autores
• Kawane Fabricio Moura , Deborah Gomes da Silva , Rafaella Cardoso Gravena , Lorena Ireno Borges , Tiago Januário da Costa , Fábio Goulart de Andrade , Daniela Cristina Ceccatto Gerardin , Rita C. Tostes , Graziela Scalianti Ceravolo
• Resumo

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  Introduction: Topiramate (TPM) is an antiepileptic drug used in children older than 2 years. This drug has been associated with increased risk markers in children and adolescents, but the late adverse effects of TPM on vascular system have not been investigated yet. Aim: To evaluate the vascular function of adult male and female rats treated with TPM during childhood. Methods: Wistar rats were treated with TPM (41 mg/kg/day) or water (CTR group) by gavage during childhood (postnatal day, 16–28). In adulthood, thoracic aorta reactivity to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (phenyl) was evaluated in the presence (Endo+) or absence (Endo-) of endothelium, with or without incubation with apocynin, tempol, indomethacin and NS398. The maximum response (maxR) for each drug was used for comparation between groups. The aortic thickness and expression of cyclooxygenases, NOX2 and p47phox were evaluated by histology and western blot, respectively [CEUA/UEL: 100/2018]. The statistical analyze was performed with ANOVA and independent test t; results expressed as mean ± standard error of the mean, p<0.05. Results: The maxR to vasodilators was similar between the groups. TPM males have higher maxR for phenyl in Endo+ [CTR: 1.87±0.09 vs TPM: 2.78±0.11; n=10-12] and Endo- [CTR: 4.11±0.08 vs TPM: 4.72±0.17; n=10-12] rings, while TPM females presented increased maxR in Endo+ rings [CTR: 1.15±0.09 vs TPM: 1.97±0.15; n=11-12]. In TPM male rats, the hyperreactivity to phenyl was abrogated by the inhibition of NADPH oxidase and COX-2, while in female rats, responses were restored only by inhibition of COX-2. In addition, TPM male rats presented aortic hypertrophy and increased expression of NOX-2 and p47phox, while TPM female rats showed increased COX-2 aortic expression. Conclusion: The treatment with TPM during childhood causes sex-specific vascular dysfunction in adulthood.

   

• Palavras-chave
• endothelial dysfunction, aortic hypertrophy, oxidative stress, inflammation
• Área Temática
• Vídeo-pôster / Sala 9 -O sistema cardiovascular sob a influência do período gestacional ou pós-gestacional ou do dimorfismo sexual

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