Topiramate Exposure During Childhood Causes Endothelial Dysfunction In Adult Male Rats

Topiramate Exposure During Childhood Causes Endothelial Dysfunction In Adult Male Rats

• Autor
• Rafaella Cardoso Gravena
• Co-autores
• Camila Borecki Vidigal , Kawane Fabricio Moura , Deborah Gomes da Silva , Lorena Ireno Borges , Daniela Cristina Ceccatto Gerardin , Fábio Goulart de Andrade , Maria do Carmo Pinho Franco , Graziela Scalianti Ceravolo
• Resumo

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  Introduction: Topiramate (TOP) is used for the treatment of epilepsy in children after 2 years of age. The TOP treatment predispose the individual to cardiovascular diseases into adulthood. However, late effects of this treatment on the vascular system hasn´t be investigated. This study aimed to evaluate: the aortic reactivity and histology in male adult rats exposed to TOP during childhood. Methods: (UEL-Ethics Committee 100/2018). Male Wistar rats were exposed to 41.0mg/kg/day of TOP or water (gavage) during childhood (postnatal day (PND) 16-28). Into adulthood (PND 120), it was evaluated the thoracic aorta reactivity to phenylephrine (phenyl) in rings with (E+) and without endothelium (E-), with or without incubation with indomethacin and apocynin; results were compared using the maximum response (maxR, g) and pD2 (-log of the concentration that causes 50% of the maxR – data not shown). The thoracic aorta thickness of the middle layer (?m) were evaluated using histological slices. Statistic: One-way ANOVA, Bonferroni post-test and independent test t; results expressed as mean±standard error of the mean and number of samples (n); differences when p<0.05. Results: Adult TOP rats presented increased maxR to phenyl on E+ [2,77±0,10 (10)] and E- [4,72±0,17 (10)] when compared to CTR E+ [1,90±0,09 (12)] and E- [4,10±0,08 (12)]. Apocynin and indomethacin reduced maxR to phenyl in TOP E+ [phenyl: 2.87 ± 0.12 (11); phenyl+indomethacin: 2.09 ± 0.14 (11); phenyl+apocynin: 2.28 ± 0.13 (11)]. The maxR in aortic rings of CTR group wasn’t affected by incubations. The aortic thickness was greater in TOP group [69.88±1.24 (8)] than in CTR group [63.90±1.26 (7)]. Conclusion: Adult male rats exposed to TOP during childhood developed vascular dysfunction, characterized by aortic hyperreactivity to phenyl in the presence and absence of endothelium. The mechanism related probably involves inflammation, oxidative stress and smooth muscle cells hypertrophy.

   

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