Braz Glauber Ruda F, Freitas Cristiane M, Nascimento Luciana, Pedroza Anderson A, da Silva Aline Isabel, Lagranha Claudia
a Laboratory of Biochemistry and Exercise Biochemistry, Centro Acadêmico de Vitoria (CAV)-Federal University of Pernambuco, Vitoria de Santo Antão, Brazil.
c Biochemistry and Physiology Graduate Program, Federal University of Pernambuco, Recife, Brazil.
Appl Physiol Nutr Metab. 2016 Apr;41(4):362-9. doi: 10.1139/apnm-2015-0494. Epub 2015 Nov 24.
Protein restriction during prenatal, postnatal, or in both periods has a close relationship with subsequent development of cardiovascular disease in adulthood. Elevated brain levels of serotonin and its metabolites have been found in malnourished states. The aim in the present study was to investigate whether treatment with fluoxetine (Fx), a selective serotonin reuptake inhibitor, mimics the detrimental effect of low-protein diet during the perinatal period on the male rat heart. Our hypothesis is that increased circulating serotonin as a result of pharmacologic treatment with Fx leads to cardiac dysfunction similar to that observed in protein-restricted rats. Male Wistar rat pups received daily subcutaneous injection of Fx or vehicle from postnatal day 1 to postnatal day 21. Male rats were euthanized at 60 days of age and the following parameters were evaluated in the cardiac tissue: mitochondrial respiratory capacity, respiratory control ratio, reactive oxygen species (ROS) production, mitochondrial membrane potential, and biomarkers of oxidative stress and antioxidant defense. We found that Fx treatment increased mitochondrial respiratory capacity (123%) and membrane potential (212%) and decreased ROS production (55%). In addition we observed an increase in the antioxidant capacity (elevation in catalase activity (5-fold) and glutathione peroxidase (4.6-fold)). Taken together, our results suggest that Fx treatment in the developmental period positively affects the mitochondrial bioenergetics and antioxidant defense in the cardiac tissue.
产前、产后或两个时期的蛋白质限制与成年后心血管疾病的后续发展密切相关。在营养不良状态下已发现大脑中血清素及其代谢产物水平升高。本研究的目的是调查选择性血清素再摄取抑制剂氟西汀（Fx）治疗是否会模拟围产期低蛋白饮食对雄性大鼠心脏的有害影响。我们的假设是，Fx药物治疗导致循环血清素增加，从而导致心脏功能障碍，类似于蛋白质限制大鼠中观察到的情况。雄性Wistar大鼠幼崽从出生后第1天到出生后第21天每天接受皮下注射Fx或赋形剂。雄性大鼠在60日龄时安乐死，并在心脏组织中评估以下参数：线粒体呼吸能力、呼吸控制率、活性氧（ROS）产生、线粒体膜电位以及氧化应激和抗氧化防御的生物标志物。我们发现，Fx治疗增加了线粒体呼吸能力（123%）和膜电位（212%），并减少了ROS产生（55%）。此外，我们观察到抗氧化能力增加（过氧化氢酶活性升高5倍，谷胱甘肽过氧化物酶升高4.6倍）。综上所述，我们的结果表明，发育时期的Fx治疗对心脏组织中的线粒体生物能量学和抗氧化防御有积极影响。
