EXPOSURE TO TOPIRAMATE DURING ADOLESCENCE PROGRAM PERMANENT VASCULAR DYSFUNCTION IN RATS

EXPOSURE TO TOPIRAMATE DURING ADOLESCENCE PROGRAM PERMANENT VASCULAR DYSFUNCTION IN RATS

• Autor
• Kawane Fabricio Moura
• Co-autores
• Camila Borecki Vidigal , Deborah Gomes da Silva , Ingrid Caroline Pinto , Juliana Silva Jezuino , João Vinícius Honório da Silva , Fábio Goulart de Andrade , Maria do Carmo Pinho Franco , Daniela Cristina Ceccatto Gerardin , Rúbia Casagrande , Graziela Scalianti Ceravolo
• Resumo

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  Topiramate (TOP) is a drug approved for migraine prophylaxis in adolescents and has been reported to predispose vascular disease in humans. Objective: The present study aimed to evaluate the aortic reactivity in male adolescent and adult rats treated with TOP during adolescence. Methods: (UEL-Ethics Committee 100/2018). Rats were treated with TOP (41 mg/kg/day, gavage) or vehicle (CTR group) from the postnatal day (PND) 28 to 50. At PND 51 and PND 120 the rats were evaluated for: thoracic aorta reactivity to phenylephrine, in the presence (E+) or absence of endothelium (E-), and acetylcholine (ACh); and aortic thickness. In serum were analyzed: the antioxidant capacity by ferric reducing antioxidant power assay (FRAP; nmol Trolox/mg of protein); endogenous antioxidant reduced glutathione (GSH; µM/mg of protein), and superoxide anion was performed through the nitroblue tetrazolium assay (NBT; OD at 620nm/mg of protein). Statistics: One-way ANOVA (and Tukey's) or independent T-test. Results were expressed as mean ± s.e.m., differences when p <0.05.  Results: At PND 51, Rmax to the phenylephrine in E+ rings was higher in TOP [2.51±0.05g; n=10] when compared to CTR [1.98±0.06g; n=10].  At PND 120, TOP and CTR aortic rings showed similar vasoconstriction. At PDN 120, TOP [7.11±0.11 n=9] presented decreased pD2 to ACh than CTR [7.48±0.07; n=9]. Also, the aortic thickness was similar between the groups at both ages. At PND 51 the redox balance was similar between the groups. At PND 120, TOP showed decreased FRAP [CTR: 1.19±0.13 vs TOP: 0.69±0.11; n=5/group] and GSH values [CTR: 0.55±0.04; n=5 vs TOP: 0.20±0.04; n=4] and increased NBT [CTR: 0.59±0.01; n=5 vs TOP: 1.45±0.23; n=5]. Conclusion: Treatment of rats with TOP during adolescence promoted permanent impairment of endothelial function probably mediated by increased oxidative stress.

   

• Palavras-chave
• Vascular reactivity, Adolescent, oxidative stress
• Modalidade
• Pôster
• Área Temática
• Disfunção endotelial