Fish oil supplementation and physical exercise during the development period increase cardiac antioxidant capacity in Wistar rats

Abstract Aim: To investigate if treadmill exercise (Ex) associated with fish oil (FO) supplementation during lactation would influence the biochemical profile as well as the oxidative balance in the hearts of male juvenile rats. Methods: Fifteen days-old rats were submitted to a daily moderate Ex training (based on their maximal running capacity) and FO supplementation for 4 weeks. Forty-eight hours after the last exercise session, blood fasting glucose and lipid profile were assessed according to the manufacturer's recommendations, while the oxidative status of the hearts was evaluated via colorimetric and absorbance-based assays. Results: FO associated with Ex decreased triglycerides (TG-79.27 ± 5.75 to 60.24 ± 6.25 mg/dL) and very-low-density lipoprotein cholesterol levels (VLDL-15.85 ± 1.15 to 12.05 ± 1.25 mg/dL) when compared to sedentary animals. FO, alone, reduced atherogenic index (AI- 1.14 ± 0.03 vs. 1.01 ± 0.04 a.u) while increased high-density lipoprotein cholesterol (HDL-43.90 ± 2.50 vs. 59.43 ± 3.15 mg/dL) of sedentary animals. Additionally, both Ex (67.3 ± 13.5 nmol/mg prot) and FO supplementation (56.6 ± 5.5 nmol/mg prot) decreased the oxidative damage to lipids in non-trained animals (105.8 ± 10.8 nmol/mg prot). The interventions also protected the protein content from oxidative stress (Ex- 5.15 ± 0.46; FO- 4.5 ± 0.5; and vehicle sedentary-7.3 ± 0.6 µmol/mg prot), while increasing the antioxidant defense and oxidative metabolism. Conclusion: Our findings suggest that intervention in juvenile rats can improve cardiac metabolism. These are the first findings to show the positive effects of the association between FO and moderate treadmill Ex during the critical period of development. We believe these results can drive early-life origins of heart disease through different avenues and, possibly, assist the development of a heart disease prevention program as well as an adjunctive therapeutic resource.

Serotonin transporter inhibition during neonatal period induces sex-dependent effects on mitochondrial bioenergetics in the rat brainstem.

The serotonin reuptake is mainly regulated by the serotonin transporters (SERTs), which are abundantly found in the raphe nuclei, located in the brainstem. Previous studies have shown that dysfunction in the SERT has been associated with several disorders, including depression and cardiovascular diseases. In this manuscript, we aimed to investigate how gender and the treatment with a serotonin selective reuptake inhibitor (SSRI) could affect mitochondrial bioenergetics and oxidative stress in the brainstem of male and female rats. Fluoxetine, our chosen SSRI, was used during the neonatal period (i.e., from postnatal Day 1 to postnatal Day 21-PND1 to PND21) in both male and female animals. Thereafter, experiments were conducted in adult rats (60 days old). Our results demonstrate that, during lactation, fluoxetine treatment modulates the mitochondrial bioenergetics in a sex-dependent manner, such as improving male mitochondrial function and female antioxidant capacity.

Safflower (Carthamus tinctorius L.) oil during pregnancy and lactation influences brain excitability and cortex oxidative status in the rat offspring.

OBJECTIVES: To evaluate how safflower oil (SFO) influences brain electrophysiology and cortical oxidative status in the offspring, mothers received a diet with SFO during brain development period. METHODS: Beginning on the 14th day of gestation and throughout lactation, rats received safflower (safflower group - SG) or soybean oil (control group - CG) in their diet. At 65 days old, cortical spreading depression (CSD) and cortex oxidative status were analyzed in the offspring. RESULTS: SG presented reduction of the CSD velocity as compared to the CG (SG: 3.24 ± 0.09; CG: 3.37 ± 0.07 mm/min). SFO reduced levels of lipid peroxidation by 39.4%. SG showed the following increases: glutathione-S-transferase, 40.8% and reduced glutathione, 34.3%. However, SFO decreased superoxide dismutase by 40.4% and catalase by 64.1%. To control for interhemispheric effects, since CSD was recorded only in the right cortex, we evaluated the oxidative status in both sides of the cortex; no differences were observed. DISCUSSION: Data show that when SFO is consumed by the female rats during pregnancy and lactation, the offspring present long-term effects on brain electrophysiology and cortical oxidative state. The present study highlights the relevance of understanding the SFO intake of pregnant and lactating mammals.

Fighting Oxidative Stress: Increased Resistance of Male Rat Cerebellum at Weaning Induced by Low Omega 6/Omega 3 Ratio in a Protein-Deficient Diet.

The cerebellum is vulnerable to malnutrition effects. Notwithstanding, it is able to incorporate higher amount of docosahexaenoic acid (DHA) than the cerebral cortex (Cx) when low n-6/n-3 fatty acid ratio is present in a multideficient diet. Considering importance of DHA for brain redox balance, we hypothesize that this cerebellum feature improves its antioxidant status compared to the Cx. A chronic malnutrition status was induced on dams before mating and kept until weaning or adulthood (offspring). A group nutritionally rehabilitated from weaning was also analyzed. Morphometric parameters, total-superoxide dismutase (t-SOD) and catalase activities, lipoperoxidation (LP), nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, reactive oxygen species (ROS), and reduced nicotinamide adenine dinucleotide/phosphate levels were assessed. Both ROS and LP levels were increased (∼53 %) in the Cx of malnourished young animals while the opposite was seen in the cerebellum (72 and 20 % of the control, respectively). Consistently, lower (∼35 %) and higher t-SOD (∼153 %) and catalase (CAT) (∼38 %) activities were respectively detected in the Cx and cerebellum compared to the control. In malnourished adult animals, redox balance was maintained in the cerebellum and recovered in the Cx (lower ROS and LP levels and higher GSH/GSSG ratio). NO production was impaired by malnutrition at either age, mainly in the cerebellum. The findings suggest that despite a multinutrient deficiency and a modified structural development, a low dietary n-6/n-3 ratio favors early antioxidant resources in the male cerebellum and indicates an important role of astrocytes in the redox balance recovery of Cx in adulthood.