Ação do ácido fólico em modelo experimental de ratas em uso de olanzapina e fluoxetina
Data
2022-12-02
Autores
Colombini, Viridiana Carolina Santos 
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: Avaliar o efeito do ácido fólico na prevenção de malformações
craniofaciais e do tubo digestivo, em ratas prenhes que receberam olanzapina e
fluoxetina. Métodos: Foram usados 18 ratas Wistar - EPM, com aproximadamente 3
meses, provenientes do Biotério Central da Unifesp e mantidos durante uma semana
em adaptação ao novo ambiente. Foram mantidos em condições adequadas à
espécie de temperatura, umidade, com 12 horas expostas à luz por dia e ciclos
noturnos de 12 horas, automaticamente controlados, com água e comida ad libitium,.
As ratas foram divididas em dois grupos, um com ingesta de ácido fólico, 50 mg/dia
por duas semanas por gavagem e outro grupo sem receber. Após este período, foi
realizada a concepção, e a fêmea que estava com líquido seminal foi considerada
fertilizada e foi marcado o dia zero da gestação. As fêmeas foram mantidas em gaiolas
sozinhas tendo sido alocadas em dois grupos: grupo que recebeu apenas o ácido
fólico, grupo que recebeu ácido fólico, fluoxetina e olanzapina e os grupos que não
receberam ácido fólico, somente os psicotrópicos. Resultados: Foram realizados os
experimentos de todos os grupos, sendo que no último Grupo, Fluoxetina+
Olanzapina+Ácido Fólico não houve fetos vivos, somente abortos. No total, foram
obtidos 71 fetos normais, incluindo os do grupo controle, bem como os que usaram
fluoxetina ou olanzapina, isoladamente. Nos prenhes que usaram a associação de
fluoxetina e olanzapina, houve 8 fetos normais, porém apenas 1 com a placenta sem
alterações, 15 fetos retidos com abortamento, 2 fetos com alterações anatômicas em
cabeça: um feto com língua disforme e um feto com fissura labial, além de alterações
histológicas intestinais em 8 fetos desse grupo. Não foram observadas imperfuração
anal e nem ausência de cauda. Observou-se à macroscopia, placenta com coloração
mais violácea, sem alteração em relação ao peso das placentas e dos fetos.
Conclusões: Observou-se sinergismo quanto aos efeitos teratogênicos na
associação dos fármacos psicotrópicos. A coadministração do ácido fólico promoveu
aumento da teratogenicidade, ao ponto de nenhuma gestação ter formado feto viável.
Objectives: Evaluate craniofacial and digestive tract malformations in pregnant rats receiving olanzapine, fluoxetine and folic acid. Methods: 18 Wistar-EPM rats from the Unifesp Bioterium, aged around 3 months, were kept for a week on an automatically controlled environment. They were kept in good conditions of temperature, humidity, water and food ad libitium, 12 hours exposed to light per day, night cycles of 12 hours. The rats were divided into 2 groups. The first group received 50 mg/day of folic acid for 2 weeks by gavage. The second group did not receive folic acid. After this period, mating was carried out. Presence of seminal fluid in rat’s vagina was considered positive for conception and scheduled as day zero of gestation. Females were kept alone in cages and kept taking or not folic acid as previously randomized. Results: Experiments were carried out for all groups, with the last Group, Fluoxetine + Olanzapine + Folic Acid not obtaining live fetuses, only abortions. In total, 71 normal fetuses were obtained, including those from the control group, as well as those who used fluoxetine or olanzapine, alone. In the fetuses that used the combination of fluoxetine and olanzapine, we have 8 normal fetuses but only 1 with the placenta without changes, 15 fetuses retained with abortion, 2 fetuses with anatomical changes in the head: a fetus with a misshapen tongue and a fetus with cleft lip with intestinal histological changes in 8 fetuses in this group. No anal perforation and no tail were observed. On macroscopy, a more violaceous colored placenta was observed, with no change in relation to the weight of the placentas and fetuses. Conclusions: Synergism regarding teratogenic effects was observed in the association of psychotropic drugs. The coadministration of folic acid promoted increased teratogenicity, to the point that no pregnancy formed a viable fetus.
Objectives: Evaluate craniofacial and digestive tract malformations in pregnant rats receiving olanzapine, fluoxetine and folic acid. Methods: 18 Wistar-EPM rats from the Unifesp Bioterium, aged around 3 months, were kept for a week on an automatically controlled environment. They were kept in good conditions of temperature, humidity, water and food ad libitium, 12 hours exposed to light per day, night cycles of 12 hours. The rats were divided into 2 groups. The first group received 50 mg/day of folic acid for 2 weeks by gavage. The second group did not receive folic acid. After this period, mating was carried out. Presence of seminal fluid in rat’s vagina was considered positive for conception and scheduled as day zero of gestation. Females were kept alone in cages and kept taking or not folic acid as previously randomized. Results: Experiments were carried out for all groups, with the last Group, Fluoxetine + Olanzapine + Folic Acid not obtaining live fetuses, only abortions. In total, 71 normal fetuses were obtained, including those from the control group, as well as those who used fluoxetine or olanzapine, alone. In the fetuses that used the combination of fluoxetine and olanzapine, we have 8 normal fetuses but only 1 with the placenta without changes, 15 fetuses retained with abortion, 2 fetuses with anatomical changes in the head: a fetus with a misshapen tongue and a fetus with cleft lip with intestinal histological changes in 8 fetuses in this group. No anal perforation and no tail were observed. On macroscopy, a more violaceous colored placenta was observed, with no change in relation to the weight of the placentas and fetuses. Conclusions: Synergism regarding teratogenic effects was observed in the association of psychotropic drugs. The coadministration of folic acid promoted increased teratogenicity, to the point that no pregnancy formed a viable fetus.
Descrição
Citação
COLOMBINI, Viridiana Carolina Santos. Ação do ácido fólico em modelo experimental de ratas em uso de olanzapina e fluoxetina. São Paulo, 2021. 64 f. Dissertação (Mestrado em Ciência Cirúrgica Interdisciplinar) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2021.