Topiramate Exposure During Childhood Causes Endothelial Dysfunction In Female Rats In The Adulthood: Role Of COX-2

Topiramate Exposure During Childhood Causes Endothelial Dysfunction In Female Rats In The Adulthood: Role Of COX-2

• Autor
• Camila Borecki Vidigal
• Co-autores
• Kawane Fabricio Moura , Deborah Gomes da Silva , Lorena Ireno Borges , Daniela Cristina Ceccatto Gerardin , Tiago Januário da Costa , Rita de Cassia Aleixo Tostes Passaglia , Maria do Carmo Pinho Franco , Graziela Scalianti Ceravolo
• Resumo

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  Introduction: Adverse conditions, such as exposure to medication, during early life may contribute to the development of diseases in the adulthood. Treatment with topiramate (TOP), an antiepileptic drug, has been associated with increased vascular risk markers in children and adolescents. However, late effects of this treatment on the vascular system have not been investigated yet. Thus, the study aimed to evaluate the vascular function of female adult rats exposed to TOP during childhood and the mechanisms involved. Methods: Female Wistar rats were gavaged with TOP (41.0 mg/kg/day) or water during childhood (postnatal day (PND) 16-28). In adulthood (PND 85, estrus phase), the thoracic aorta reactivity to phenylephrine (phenyl) was evaluated in the presence (E+) or absence of endothelium, with or without incubation with indomethacin, apocynin and tempol. The comparison between the groups was made using the maximum response (maxR, g) and pD2 (not shown) for the agonist. The expression of cyclooxygenase (COX) 2 was analyzed by Western Blot. Data were analyzed with Two- or One-Way ANOVA and Bonferroni post-test; the results expressed as mean ± standard error of the mean, differences were considered when p<0.05. Ethics Committee of UEL: 100/2018. Results: In adult rats, the childhood exposure to TOP increased the aortic response to phenyl only E+ rings when compared with the CTR [CTR:1.15±0.08 (12)] vs TOP:1.96±0.14 (12)]. Indomethacin reduced the Rmax to phenyl in E+ rings from TOP rats [TOP:1.95±0.17 (10) vs TOP-INDO:1.28 ±0,10 (10)]. Apocynin and tempol did not change maxR to phenyl in CTR or TOP E+ rings.  The TOP aortic expression of COX-2 [CTR: 0.02±0.00 (4) vs TOP:0.04±0.01 (4)] was higher than in CTR. Conclusion: Female rats treated with TOP during childhood presented endothelial dysfunction, characterized by hyperreactivity to Phenyl with involvement of the COX-2.

   

• Palavras-chave
• developmental theory of health and disease, vascular reactivity, childhood
• Modalidade
• Pôster
• Área Temática
• Disfunção endotelial