Embryo-toxicity of docosahexaenoic and eicosapentaenoic acids: In vivo and in silico investigations using the chick embryo model

• Published in: Biomedicine & pharmacotherapy 2021-04, Vol.136, p.111218-111218, Article 111218
• Main Authors: Salari, Zohreh, Tavakkoli, Hadi, Khosravi, Ahmad, Karamad, Elahe, Salarkia, Ehsan, Ansari, Mehdi, Dabiri, Shahriar, Mortazaeizdeh, Abbas, Mosallanejad, Seyedeh Saedeh, Sharifi, Fatemeh
• Format: Article
• Language: English
• Subjects: Apoptosis; Chick embryo; Docosahexaenoic acid; Eicosapentaenoic acid; In silico omega-3
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111218

[Display omitted] •Embryo toxicity of omega-3 associated with various pathological lesions.•Omega-3 lesions occurred mainly in the respiratory and cardiovascular systems.•Vascular apoptosis plays important role in the embryo toxicity of omega-3.•Omega-3 increases Bax and decreases Bcl-2 expressions in chick’s YSM.•EPA is predicted to affect BAX and Bcl-2 more than DHA. The objective of the current study was to evaluate the embryo-toxicity of omega-3 fatty acids. Firstly, the embryo-toxicity of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA), as well as their interaction with Bcl-2 family members, were predicted using an in silico assay. In the next step, the embryonic pathological lesions and amniotic fluid biochemical changes following omega-3 treatment were investigated using a chick embryo model. Finally, the drug's vascular apoptotic effect on the chick's yolk sac membrane (YSM) was assessed. In silico simulations revealed the embryo-toxicity, tissue-toxicity (respiratory and cardiovascular), and vascular-toxicity (apoptotic activity) of DHA and EPA. There was also an accurate interaction between DHA and EPA with Bax (Binding affinity: -7.6 and -10.6 kcal/mol) and Bcl-2 (Binding affinity: -8.0 and -12.2 kcal/mol), respectively. Moreover, DHA and EPA administrations were related to various adverse consequences, including weight loss and lesions in the respiratory and cardiovascular systems. Histopathological findings consisted of pulmonary edema, airway dilatation, increased interstitial tissue, and hyperemia in the lungs, heart, liver, kidney, and brain. Morphometric evaluation of the YSM vasculature revealed that the vascular apoptotic effect of omega-3was associated with a significant reduction in mean capillary area. In immunohistochemistry assay, increased expression of BAX and low expression of Bcl-2 affirmed apoptosis in YSM vessels. According to the results of this study, one could confirm that the possible embryo-toxicity of omega-3 was approved by data presented in this research. The obtained results also support the suspicion that alteration of the apoptotic-related proteins in vessels is an essential pathway in embryo-toxicity of omega-3.