scholarly journals Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice

2020 ◽  
Vol 19 (3) ◽  
pp. 637-643 ◽  
Author(s):  
Yasar Tastemur ◽  
Erkan Gumus ◽  
Merve Ergul ◽  
Mustafa Ulu ◽  
Recep Akkaya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Converting Enzyme ◽  
Brain Tissue ◽  
Ace Inhibitor ◽  
Neuronal Damage ◽  
Epileptic Seizures ◽  
Neuronal Injury ◽  
Converting Enzyme ◽  
Positive Effects ◽  
The Brain

Purpose: To evaluate the effects of an angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole (PTZ)-induced seizures and post-seizure hippocampal injury. Materials: Thirty-five male Balb-c mice weighing 30 - 33 g were divided into control, saline PTZ, s(erum physiologic 1 ml/kg as solvent), positive control (valproic acid 200 mg/kg), captopril (25 mg/kg/day for 7 days), and captopril (50 mg/kg/day for 7 days) groups. PTZ (60 mg/kg) was administered thirty minutes after medication administration to induce epileptic seizures. The animals were observed for 30 min to record Racine stages, the time of the first myoclonic jerk (FMJ), and the occurrence of the first generalized tonic-clonic seizure (GTCS). Cornu Ammonis (CA)1, CA2, CA3, and the dentate gyrus (DG) of the hippocampus underwent histopathological examinations. The levels of total oxidant status (TOS), oxidative stress markers (total antioxidant status, TAS), and oxidative stress index (OSI) were measured in the brain tissue. Results: Compared to PTZ group, 25 mg/kg captopril decreased seizure scores and delayed FMJ and GTCS (p < 0.05). Histopathological assessment demonstrated that both 25 and 50 mg/kg captopril alleviated neuronal injury in CA1, CA2, CA3, and DG compared to PTZ (p < 0.05). Also, TOS and OSI levels in the brain tissue were reduced by both 25 and 50 mg/kg doses of captopril (p < 0.05). Conclusion: Captopril favorably improves epileptic seizure parameters and acts against post-seizure neuronal injury in the hippocampus. Captopril may be a drug of choice in epileptic individuals with hypertension. Keywords: Captopril, Angiotensin-converting enzyme, Epilepsy, Pentylenetetrazole, Neuronal damage

scholarly journals Fangchinoline ameliorates the expressions of angiogenic molecule in cerebral ischemia induced neuronal degeneration in neonatal rats

2018 ◽  
Vol 9 (1) ◽  
pp. 117-122
Author(s):  
Han Daicheng ◽  
Xia Shiwen ◽  
Zhu Huaping ◽  
Liu Yong ◽  
Zhou Qianqian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Neuronal Degeneration ◽  
Neuronal Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neonatal Rats ◽  
Markers Of Oxidative Stress ◽  
The Brain

AbstractBackgroundPresent investigation evaluates the beneficial effect of fangchinoline on cerebral ischemia induced neuronal degeneration in neonatal rats and also postulates the possible mechanism of its action.MethodologyCerebral ischemia was produced by the ligation of right common carotid artery in neonatal rats on postnatal day 5 (P5) and further pups were treated with fangchinoline 3, 10 and 30 mg/kg, i.p. for the period of 3 days. Effect of fangchinoline was estimated by determining the brain injury and enzyme linked immunosorbent assay (ELISA) method was used for the estimation of pro-inflammatory mediators and markers of oxidative stress in the cerebral tissues of neonatal rats. Moreover western blot assay and histopathology study was also performed on the brain tissue.ResultsResult of this investigation reveals that the percentage of brain injury significantly reduces and enhancement of myelin basic protein in the cerebral tissues of fangchinoline than ischemic group. Treatment with fangchinoline attenuates the altered level of proinflammatory mediators and markers of oxidative stress in the cerebral tissue of cerebral ischemia induced neuronal injury neonatal rats. Moreover expressions of inducible nitric oxide synthtase (iNOS), vascular endothelial growth factor (VEGF), p53 and nuclear receptor factor-2 (Nrf2) in the brain tissue attenuated by fangchinoline treated group.ConclusionIn conclusion, fangchinoline ameliorates the cerebral ischemia induced neuronal injury in neonatal rats by enhancing angiogenesis molecules.

scholarly journals Angiotensin-converting enzyme 2 (ACE2) is upregulated in Alzheimer’s disease brain

2020 ◽  
Author(s):  
Qiyue Ding ◽  
Nataliia V. Shults ◽  
Brent T. Harris ◽  
Yuichiro J. Suzuki
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Protein Expression ◽  
Neurodegenerative Disorder ◽  
Host Cells ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The Brain

AbstractAlzheimer’s disease is a chronic neurodegenerative disorder and represents the main cause of dementia. Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. In COVID-19, neurological manifestations have been reported to occur. The present study demonstrates that the protein expression level of ACE2 is upregulated in the brain of Alzheimer’s disease patients. The increased ACE2 expression is not age-dependent, suggesting the direct relationship between Alzheimer’s disease and the ACE2 expression. Oxidative stress has been implicated in the pathogenesis of Alzheimer’s disease, and Alzheimer’s disease brains examined in this study also exhibited higher carbonylated proteins as well as increased thiol oxidation state of peroxiredoxin 6 (Prx6). The positive correlation was found between the increased ACE2 protein expression and oxidative stress in Alzheimer’s disease brain. Thus, the present study reveals the relationships between Alzheimer’s disease and ACE2, the receptor for SARS-CoV-2. These results warrant monitoring Alzheimer’s disease patients with COVID-19 carefully for the possible higher viral load in the brain and long-term adverse neurological consequences.

scholarly journals SARS-CoV-2 Coronavirus Spike Protein-Induced Apoptosis, Inflammatory, and Oxidative Stress Responses in THP-1-Like-Macrophages: Potential Role of Angiotensin-Converting Enzyme Inhibitor (Perindopril)

2021 ◽  
Vol 12 ◽  
Author(s):  
Tlili Barhoumi ◽  
Bandar Alghanem ◽  
Hayat Shaibah ◽  
Fatmah A. Mansour ◽  
Hassan S. Alamri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Converting Enzyme Inhibitor ◽  
Ace Inhibitor ◽  
Enzyme Inhibitor ◽  
Ros Generation ◽  
Converting Enzyme ◽  
S Protein ◽  
Mhc Ii ◽  
Huvec Cells

A purified spike (S) glycoprotein of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) coronavirus was used to study its effects on THP-1 macrophages, peripheral blood mononuclear cells (PBMCs), and HUVEC cells. The S protein mediates the entry of SARS-CoV-2 into cells through binding to the angiotensin-converting enzyme 2 (ACE2) receptors. We measured the viability, intracellular cytokine release, oxidative stress, proinflammatory markers, and THP-1-like macrophage polarization. We observed an increase in apoptosis, ROS generation, MCP-1, and intracellular calcium expression in the THP-1 macrophages. Stimulation with the S protein polarizes the THP-1 macrophages towards proinflammatory futures with an increase in the TNFα and MHC-II M1-like phenotype markers. Treating the cells with an ACE inhibitor, perindopril, at 100 µM reduced apoptosis, ROS, and MHC-II expression induced by S protein. We analyzed the sensitivity of the HUVEC cells after the exposure to a conditioned media (CM) of THP-1 macrophages stimulated with the S protein. The CM induced endothelial cell apoptosis and MCP-1 expression. Treatment with perindopril reduced these effects. However, the direct stimulation of the HUVEC cells with the S protein, slightly increased HIF1α and MCP-1 expression, which was significantly increased by the ACE inhibitor treatment. The S protein stimulation induced ROS generation and changed the mitogenic responses of the PBMCs through the upregulation of TNFα and interleukin (IL)-17 cytokine expression. These effects were reduced by the perindopril (100 µM) treatment. Proteomic analysis of the S protein stimulated THP-1 macrophages with or without perindopril (100 µM) exposed more than 400 differentially regulated proteins. Our results provide a mechanistic analysis suggesting that the blood and vascular components could be activated directly through S protein systemically present in the circulation and that the activation of the local renin angiotensin system may be partially involved in this process.GraphicalSuggested pathways that might be involved at least in part in S protein inducing activation of inflammatory markers (red narrow) and angiotensin-converting enzyme inhibitor (ACEi) modulation of this process (green narrow).

scholarly journals Protein Expression of Angiotensin-Converting Enzyme 2 (ACE2) is Upregulated in Brains with Alzheimer’s Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1687
Author(s):  
Qiyue Ding ◽  
Nataliia V. Shults ◽  
Sergiy G. Gychka ◽  
Brent T. Harris ◽  
Yuichiro J. Suzuki
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Protein Expression ◽  
Neurodegenerative Disorder ◽  
Host Cells ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The Brain

Alzheimer’s disease is a chronic neurodegenerative disorder and represents the main cause of dementia globally. Currently, the world is suffering from the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. In COVID-19, neurological manifestations have been reported to occur. The present study demonstrates that the protein expression level of ACE2 is upregulated in the brain of patients with Alzheimer’s disease. The increased ACE2 expression is not age-dependent, suggesting the direct relationship between Alzheimer’s disease and ACE2 expression. Oxidative stress has been implicated in the pathogenesis of Alzheimer’s disease, and brains with the disease examined in this study also exhibited higher carbonylated proteins, as well as an increased thiol oxidation state of peroxiredoxin 6 (Prx6). A moderate positive correlation was found between the increased ACE2 protein expression and oxidative stress in brains with Alzheimer’s disease. In summary, the present study reveals the relationships between Alzheimer’s disease and ACE2, the receptor for SARS-CoV-2. These results suggest the importance of carefully monitoring patients with both Alzheimer’s disease and COVID-19 in order to identify higher viral loads in the brain and long-term adverse neurological consequences.

scholarly journals A clinical dose of angiotensin-converting enzyme (ACE) inhibitor and heterozygous ACE deletion exacerbate Alzheimer's disease pathology in mice

2019 ◽  
Vol 294 (25) ◽  
pp. 9760-9770 ◽  
Author(s):  
Shuyu Liu ◽  
Fujiko Ando ◽  
Yu Fujita ◽  
Junjun Liu ◽  
Tomoji Maeda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Precursor Protein ◽  
Causative Role ◽  
Converting Enzyme ◽  
Clinical Dose

Inhibition of angiotensin-converting enzyme (ACE) is a strategy used worldwide for managing hypertension. In addition to converting angiotensin I to angiotensin II, ACE also converts neurotoxic β-amyloid protein 42 (Aβ42) to Aβ40. Because of its neurotoxicity, Aβ42 is believed to play a causative role in the development of Alzheimer's disease (AD), whereas Aβ40 has neuroprotective effects against Aβ42 aggregation and also against metal-induced oxidative damage. Whether ACE inhibition enhances Aβ42 aggregation or impairs human cognitive ability are very important issues for preventing AD onset and for optimal hypertension management. In an 8-year longitudinal study, we found here that the mean intelligence quotient of male, but not female, hypertensive patients taking ACE inhibitors declined more rapidly than that of others taking no ACE inhibitors. Moreover, the sera of all AD patients exhibited a decrease in Aβ42-to-Aβ40–converting activity compared with sera from age-matched healthy individuals. Using human amyloid precursor protein transgenic mice, we found that a clinical dose of an ACE inhibitor was sufficient to increase brain amyloid deposition. We also generated human amyloid precursor protein/ACE+/− mice and found that a decrease in ACE levels promoted Aβ42 deposition and increased the number of apoptotic neurons. These results suggest that inhibition of ACE activity is a risk factor for impaired human cognition and for triggering AD onset.

scholarly journals High-fat diet-induced obesity and impairment of brain neurotransmitter pool

2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Tissue ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Obese Group ◽  
Control Group ◽  
High Fat ◽  
Brain Neurotransmitter ◽  
The Brain ◽  
Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

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