Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil.
Health Sciences Graduate Program, State University of Londrina, Londrina, Paraná, Brazil.
Life Sci. 2016 May 1;152:165-70. doi: 10.1016/j.lfs.2016.03.042. Epub 2016 Mar 26.
Fluoxetine (FLX) is an antidepressant worldwide prescribed throughout life stages, including pregnancy and breastfeeding. Out of pregnancy, the combination of FLX with fish oil (FO) and folic acid (FA) is carried to enhance the therapeutic activity and reduce the side effects of the antidepressant. During pregnancy, FO and FA have been used to promote fetal development, and reduce, in mother, the risk of gestational and post-pregnancy depression. To evaluate if maternal exposure during pregnancy and lactation to FLX associated with FO or FA would prevent the antidepressant side effects in aorta reactivity and nitric oxide metabolites (NOx) plasmatic levels. We also sought to understand, in female offspring, the vascular effects of intrauterine and lactation exposure to FO and FA monotherapy.
Wistar rats were treated with water (control group), FLX (5mg/kg/day), FO (1.3g/kg/day), FA (3mg/kg/day), FLX+FO and FLX+FA, throughout pregnancy and lactation. On adulthood, in female offspring were evaluated the vascular reactivity to phenylephrine (Phe), the NOx and homocysteine (HCY) plasmatic levels.
The developmental exposure to the associations of FO or FA with FLX did not correct the aortic hyporreactivity and increased NOx levels induced by intrauterine and lactation exposure to FLX. Also, isolated exposure to FO and FA did not interfere with Phe-induced aortic contraction and neither interferes with NOx and HCY plasmatic levels.
The developmental exposure to FO and FA was safe for vascular function of female offspring but did not prevent the vascular effects of FLX-exposure.
氟西汀（FLX）是一种在全球范围内用于治疗各年龄段抑郁症的抗抑郁药，包括妊娠期和哺乳期。在妊娠期外，FLX 与鱼油（FO）和叶酸（FA）联合使用可增强治疗效果并减少抗抑郁药的副作用。在妊娠期，FO 和 FA 已被用于促进胎儿发育，并降低母亲妊娠期和产后抑郁的风险。本研究旨在评估母亲在妊娠期和哺乳期暴露于 FLX 联合 FO 或 FA 是否可以预防抗抑郁药引起的主动脉反应性和一氧化氮代谢物（NOx）血浆水平的副作用。我们还试图了解宫内和哺乳期暴露于 FO 和 FA 单药治疗对雌性后代的血管影响。
Wistar 大鼠在整个妊娠期和哺乳期接受水（对照组）、FLX（5mg/kg/天）、FO（1.3g/kg/天）、FA（3mg/kg/天）、FLX+FO 和 FLX+FA 治疗。在成年期，评估雌性后代对苯肾上腺素（Phe）的血管反应性、NOx 和同型半胱氨酸（HCY）的血浆水平。
与 FO 或 FA 的联合暴露并未纠正宫内和哺乳期暴露于 FLX 引起的主动脉低反应性和 NOx 水平升高。此外，FO 和 FA 的单独暴露不会干扰 Phe 引起的主动脉收缩，也不会干扰 NOx 和 HCY 的血浆水平。
FO 和 FA 的发育暴露对雌性后代的血管功能是安全的，但不能预防 FLX 暴露引起的血管作用。
