Protective effects of estrogen against cardiovascular disease mediated via oxidative stress in the brain

Lagranha, Cláudia Jacques; Silva, Tercya Lucidi Araujo; Silva, Severina Cássia A.; Braz, Glauber Rudá Feitoza; Silva, Aline Isabel da; Fernandes, Mariana P.; Sellitti, Donald F.

doi:10.1016/j.lfs.2017.11.043

Cited by 57 publications

(40 citation statements)

References 87 publications

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“…E 2 treatment also reduced the activity of NADPH oxidase, and improved cytosolic and mitochondrial antioxidant enzymatic activities under CIH exposure in the brain cortex . These results are consistent with the antioxidant effects of E 2 …”

Section: Introductionsupporting

confidence: 84%

“…2 These results are consistent with the antioxidant effects of E 2 . 17,18 E 2 receptors α and β (ERα and ERβ) are ligand-activated transcription factors able to reduce mitochondrial ROS production and increase oxidative phosphorylation, 19,20 leading to substantial interest in the potential clinical use of selective ERα or ERβ agonists in postmenopausal women 22 or in the context of neurodegenerative disorders. 23,24 ERα and ERβ are expressed in the central and peripheral nervous system.…”

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confidence: 99%

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Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats

et al. 2019

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Aim Chronic intermittent hypoxia (CIH) induces systemic (hypertension) and central alterations (mitochondrial dysfunction underlying cognitive deficits). We hypothesized that agonists of oestradiol receptors (ER) α and β prevent CIH‐induced hypertension and brain mitochondrial dysfunction. Methods Ovariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh), the ERα agonist propylpyraoletriol (PPT — 30 μg/kg/day) or the ERβ agonist diarylpropionitril (DPN — 100 μg/kg/day). Animals were exposed to CIH (21%‐10% FIO2 — 10 cycles/hour – 8 hours/day – 7 days) or normoxia. Arterial blood pressure was measured after CIH or normoxia exposures. Mitochondrial respiration and H2O2 production were measured in brain cortex with high‐resolution respirometry, as well as activity of complex I and IV of the electron transport chain, citrate synthase, pyruvate, and lactate dehydrogenase (PDH and LDH). Results Propylpyraoletriol but not DPN prevented the rise of arterial pressure induced by CIH. CIH exposures decreased O2 consumption, complex I activity, and increased H2O2 production. CIH had no effect on citrate synthase activity, but decreased PDH activity and increased LDH activity indicating higher anaerobic glycolysis. Propylpyraoletriol and DPN treatments prevented all these alterations. Conclusions We conclude that in OVX female rats, the ERα agonist prevents from CIH‐induced hypertension while both ERα and ERβ agonists prevent the brain mitochondrial dysfunction and metabolic switch induced by CIH. These findings may have implications for menopausal women suffering of sleep apnoea regarding hormonal therapy.

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Section: Introductionsupporting

confidence: 84%

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confidence: 99%

Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats

et al. 2019

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“…The correlation between estradiol and ceramide raises the possibility that changes in the availability of certain ceramide species [e.g. ceramide (d18:1/24:1)] might be implicated in the reported cardioprotective, antihypertensive and neuroprotective effects of estradiol [40-42]. In this context, it is important to point out that increased ceramide levels have been consistently linked to heightened risk of myocardial infarction and stroke [43].…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma ceramide levels in post-menopausal women

Vozella

Basit

Piras

et al. 2018

Preprint

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“…Disturbances in redox homeostasis also provoke plasma membrane oxidation (Halliwell & Gutteridge, 2015;Lagranha et al 2017), blood-brain barrier (BBB) disruption (Pun et al 2009) and neural-parenchymal damage (Terraneo et al 2017). However, in a translational perspective, it is unknown whether excessive ROS production drives the reduction in the human brain blood flow via reduced NO bioavailability and leads to neural-parenchymal damage as no study has simultaneously quantified human CBF and transcerebral exchanges of NO end-products, oxidant, antioxidant and neural-parenchymal damage markers under IH.…”

Section: Introductionmentioning

confidence: 99%

Human brain blood flow and metabolism during isocapnic hyperoxia: the role of reactive oxygen species

Mattos

Campos

Rocha

et al. 2018

The Journal of Physiology

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Key points It is unknown whether excessive reactive oxygen species (ROS) production drives the isocapnic hyperoxia (IH)‐induced decline in human cerebral blood flow (CBF) via reduced nitric oxide (NO) bioavailability and leads to disruption of the blood–brain barrier (BBB) or neural‐parenchymal damage. Cerebral metabolic rate for oxygen (CMRnormalO2) and transcerebral exchanges of NO end‐products, oxidants, antioxidants and neural‐parenchymal damage markers were simultaneously quantified under IH with intravenous saline and ascorbic acid infusion. CBF and CMR normalO2 were reduced during IH, responses that were followed by increased oxidative stress and reduced NO bioavailability when saline was infused. No indication of neural‐parenchymal damage or disruption of the BBB was observed during IH. Antioxidant defences were increased during ascorbic acid infusion, while CBF, CMR normalO2, oxidant and NO bioavailability markers remained unchanged. ROS play a role in the regulation of CBF and metabolism during IH without evidence of BBB disruption or neural‐parenchymal damage. Abstract To test the hypothesis that isocapnic hyperoxia (IH) affects cerebral blood flow (CBF) and metabolism through exaggerated reactive oxygen species (ROS) production, reduced nitric oxide (NO) bioavailability, disturbances in the blood–brain barrier (BBB) and neural‐parenchymal homeostasis, 10 men (24 ± 1 years) were exposed to a 10 min IH trial (100% O2) while receiving intravenous saline and ascorbic acid (AA, 3 g) infusion. Internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF) and total CBF (tCBF, Doppler ultrasound) were determined. Arterial and right internal jugular venous blood was sampled to quantify the cerebral metabolic rate of oxygen (CMRnormalO2), transcerebral exchanges (TCE) of NO end‐products (plasma nitrite), antioxidants (AA and AA plus dehydroascorbic acid (AA+DA)) and oxidant biomarkers (thiobarbituric acid‐reactive substances (TBARS) and 8‐isoprostane), and an index of BBB disruption and neuronal‐parenchymal damage (neuron‐specific enolase; NSE). IH reduced ICABF, tCBF and CMR normalO2, while VABF remained unchanged. Arterial 8‐isoprostane and nitrite TCE increased, indicating that CBF decline was related to ROS production and reduced NO bioavailability. AA, AA+DA and NSE TCE did not change during IH. AA infusion did not change the resting haemodynamic and metabolic parameters but raised antioxidant defences, as indicated by increased AA/AA+DA concentrations. Negative AA+DA TCE, unchanged nitrite, reductions in arterial and venous 8‐isoprostane, and TBARS TCE indicated that AA infusion effectively inhibited ROS production and preserved NO bioavailability. Similarly, AA infusion prevented IH‐induced decline in regional and total CBF and re‐established CMR normalO2. These findings indicate that ROS play a role in CBF regulation and metabolism during IH without evidence of BBB disruption or neural‐parenchymal damage.

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Protective effects of estrogen against cardiovascular disease mediated via oxidative stress in the brain

Cited by 57 publications

References 87 publications

Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats

Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats

Elevated plasma ceramide levels in post-menopausal women

Human brain blood flow and metabolism during isocapnic hyperoxia: the role of reactive oxygen species

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