title: Does fish oil or folic acid prevent vascular changes in female progeny caused by maternal exposure to fluoxetine?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil.
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Higashi
authors.affiliation: Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil.
authors.forename: Andressa K
authors.initials: AK
authors.lastname: Matsumoto
authors.affiliation: Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil.
authors.forename: Juliana G
authors.initials: JG
authors.lastname: Gameiro
authors.affiliation: Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil.
authors.forename: Kawane F
authors.initials: KF
authors.lastname: Moura
authors.affiliation: Health Sciences Graduate Program, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Higachi
authors.affiliation: Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil.
authors.forename: Leticia C
authors.initials: LC
authors.lastname: Oliveira
authors.affiliation: Health Sciences Graduate Program, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Décio S
authors.initials: DS
authors.lastname: Barbosa
authors.affiliation: Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil.
authors.forename: Estefânia G
authors.initials: EG
authors.lastname: Moreira
authors.affiliation: Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Brazil. Electronic address: gsceravolo@uel.br.
authors.forename: Graziela S
authors.initials: GS
authors.lastname: Ceravolo
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity*; D001808:Blood Vessels / Q000187:drug effects*; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use*; D005473:Fluoxetine / Q000633:toxicity*; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D007774:Lactation; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005395:Fish Oils; D014662:Vasoconstrictor Agents; D005473:Fluoxetine; D006710:Homocysteine; D010656:Phenylephrine; D009569:Nitric Oxide; D005492:Folic Acid
keywords: Aorta reactivity; Endothelium; Nitric oxide; Pregnancy; Selective serotonin reuptake inhibitor