scholarly journals Anti-Inflammatory Properties of Drugs Used to Control COVID-19 and their Effects on the Renin-Angiotensin System and Angiotensin-Converting Enzyme-2

2020 ◽  
Vol 23 ◽  
pp. 259-277
Author(s):  
Hamed Gilzad-Kohan ◽  
Fakhreddin Jamali
Keyword(s):  
Survival Rates ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
Reactive Protein ◽  
Crucial Component ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Severity Of The Disease

Covid-19 infection is associated with systemic inflammation, as do other infections. COVID-19 in some patients is associated with hyperinflammatory responses, which might lead to a cytokine storm. This phenomenon plays a major role in COVID-19 severity and death, and usually associated with poor disease prognosis. Higher levels of inflammatory hallmarks including C-reactive protein, ferritin, D-dimers, and cytokines such as L-6, IL-10, and TNF-α has been observed in severe cases of the disease. Many anti-viral drugs have been tried to eradicate the virus, none were proven fully effective. Supportive care and management of the complications that are caused mainly by inflammation might be the key element for greater survival rates and shorter periods of mechanical ventilation and overall hospitalization. However, the efficacy of these treatments still needs well-planned clinical trials. In such trials, careful attention must be paid to the duration of the treatment, the onset of beneficial effects, and the severity of the disease, otherwise, the outcomes may still remain inconclusive. Herein, we present a review of the current drugs, which are being used in the management of the disease and their anti-inflammatory properties. We also investigated if these drugs directly interact with ACE 2, which is a crucial component of the virus entry to the cells.

scholarly journals ACE2 activator diminazene aceturate exerts renoprotective effects in gentamicin-induced acute renal injury in rats

2020 ◽  
Vol 134 (23) ◽  
pp. 3093-3106
Author(s):  
Tatiane Cristine Silva de Almeida ◽  
Katharina Lanza ◽  
Roberta da Silva Filha ◽  
Leda Maria de Castro C. Campos ◽  
Esdras G. Fonseca ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Renal Diseases ◽  
Therapeutic Effects ◽  
Acute Renal Injury ◽  
Diminazene Aceturate ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
Tnf Α

Abstract Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin–Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.

The anti-inflammatory effect of exercise

2005 ◽  
Vol 98 (4) ◽  
pp. 1154-1162 ◽  
Author(s):  
Anne Marie W. Petersen ◽  
Bente Klarlund Pedersen
Keyword(s):  
Insulin Resistance ◽  
Muscle Fibers ◽  
The Body ◽  
Low Grade ◽  
Regular Exercise ◽  
Beneficial Effects ◽  
Reactive Protein ◽  
The Metabolic Syndrome ◽  
Tnf Α ◽  
Anti Inflammatory

Regular exercise offers protection against all-cause mortality, primarily by protection against cardiovascular disease and Type 2 diabetes mellitus. The latter disorders have been associated with chronic low-grade systemic inflammation reflected by a two- to threefold elevated level of several cytokines. Adipose tissue contributes to the production of TNF-α, which is reflected by elevated levels of soluble TNF-α receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein. We suggest that TNF-α rather than IL-6 is the driver behind insulin resistance and dyslipidemia and that IL-6 is a marker of the metabolic syndrome, rather than a cause. During exercise, IL-6 is produced by muscle fibers via a TNF-independent pathway. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits the production of the proinflammatory cytokine TNF-α. In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. We suggest that regular exercise induces suppression of TNF-α and thereby offers protection against TNF-α-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine that is produced and released by contracting skeletal muscle fibers, exerting its effects in other organs of the body. Here we suggest that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.

scholarly journals Alamandine: Potential Protective Effects in SARS-CoV-2 Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Ava Soltani Hekmat ◽  
Kazem Javanmardi
Keyword(s):  
Pulmonary Fibrosis ◽  
Renin Angiotensin System ◽  
The Body ◽  
Host Cells ◽  
Protective Effects ◽  
Ang Ii ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Anti Inflammatory ◽  
G Protein Coupled

Coronavirus disease 2019 (COVID-19) can occur due to contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has no confined treatment and, consequently, has high hospitalization and mortality rates. Moreover, people who contract COVID-19 present systemic inflammatory spillover. It is now known that COVID-19 pathogenesis is linked to the renin-angiotensin system (RAS). COVID-19 invades host cells via the angiotensin-converting enzyme 2 (ACE2) receptor—as such, an individual’s susceptibility to COVID-19 increases alongside the upregulation of this receptor. COVID-19 has also been associated with interstitial pulmonary fibrosis, which leads to acute respiratory distress, cardiomyopathy, and shock. These outcomes are thought to result from imbalances in angiotensin (Ang) II and Ang-(1-7)/alamandine activity. ACE2, Ang-(1-7), and alamandine have potent anti-inflammatory properties, and some SARS-CoV-2 patients exhibit high levels of ACE2 and Ang-(1-7). This phenomenon could indicate a failing physiological response to prevent or reduce the severity of inflammation-mediated pulmonary injuries. Alamandine, which is another protective component of the RAS, has several health benefits owing to its antithrombogenic, anti-inflammatory, and antifibrotic characteristics. Alamandine alleviates pulmonary fibrosis via the Mas-related G protein-coupled receptor D (MrgD). Thus, a better understanding of this pathway could uncover novel pharmacological strategies for altering proinflammatory environments within the body. Following such strategies could inhibit fibrosis after SARS-CoV-2 infection and, consequently, prevent COVID-19.

scholarly journals The Anti-Inflammatory Effect of Taurine on Cardiovascular Disease

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2847 ◽  
Author(s):  
Tawar Qaradakhi ◽  
Laura Kate Gadanec ◽  
Kristen Renee McSweeney ◽  
Jemma Rose Abraham ◽  
Vasso Apostolopoulos ◽  
...  
Keyword(s):  
Sulfonic Acid ◽  
Renin Angiotensin System ◽  
Animal Tissues ◽  
Cellular Functions ◽  
Protein Amino Acid ◽  
Angiotensin System ◽  
Beneficial Effects ◽  
Ion Movement ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Taurine is a non-protein amino acid that is expressed in the majority of animal tissues. With its unique sulfonic acid makeup, taurine influences cellular functions, including osmoregulation, antioxidation, ion movement modulation, and conjugation of bile acids. Taurine exerts anti-inflammatory effects that improve diabetes and has shown benefits to the cardiovascular system, possibly by inhibition of the renin angiotensin system. The beneficial effects of taurine are reviewed.

scholarly journals The relation between COVID-19 and cerebrovascular diseases

2021 ◽  
Author(s):  
Francisco Gabriel Cabral Oliveira ◽  
Juliana Paiva Ribeiro Moura ◽  
Matheus Henrique Oliveira ◽  
Mylena Teles de Jesus
Keyword(s):  
Renin Angiotensin System ◽  
Cerebrovascular Diseases ◽  
C Reactive Protein ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Reactive Protein ◽  
Cerebrovascular Events ◽  
The Central Nervous System ◽  
The Brain ◽  
Neurological System

Introduction: Covid-19 is characterized by respiratory syndrome and has symptoms that affect the central nervous system such as headache, anosmia, hypercoagulability, etc. In this sense, it is known that the virus shows tropism by the receptors of the angiotensin-converting enzyme 2 (ACE2), becoming a gateway to the neurological system, which can cause complications. Is to relate the infection by COVID-19 and the increase in cerebrovascular diseases. Methods: A literature review was carried out using search for scientific articles in PubMed, in April / 2021, with a filter in the last 5 years, using the descriptors “Covid”, “Cerebrovascular Diseases” and “Man” associated with the Boolean operator AND. Results: 53 articles were found, of which 19 were selected for research. There is a higher frequency of neurological symptoms in patients with COVID-19 than in patients without the disease. The effect of binding the virus to ACE2 receptors is to activate a cascade of cytokines, which tends to lead to serious complications. For this reason, severe coagulopathies can be caused, increasing products of the degradation of C-reactive protein, D Dimer, fibrinogen and thrombocytopenia. The increase in cerebrovascular events also occurs because the antithrombotic, neuroprotective, antihypertensive effects, among others, of the alternative renin-angiotensin system in the brain are interrupted due to COVID-19. Conclusion: It was seen that cerebrovascular events are related to the course of COVID-19, in which patients may develop several serious complications, such as encephalitis, strokes and vascular thrombosis. Thus, the pathophysiology of this disease is related to an inflammatory process.

Angiotensin 1–7 mediates renoprotection against diabetic nephropathy by reducing oxidative stress, inflammation, and lipotoxicity

2014 ◽  
Vol 306 (8) ◽  
pp. F812-F821 ◽  
Author(s):  
Jun Mori ◽  
Vaibhav B. Patel ◽  
Tharmarajan Ramprasath ◽  
Osama Abo Alrob ◽  
Jessica DesAulniers ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
Osmotic Pumps ◽  
Characteristic Features ◽  
Transcription 3

The renin-angiotensin system, especially angiotensin II (ANG II), plays a key role in the development and progression of diabetic nephropathy. ANG 1–7 has counteracting effects on ANG II and is known to exert beneficial effects on diabetic nephropathy. We studied the mechanism of ANG 1–7-induced beneficial effects on diabetic nephropathy in db/db mice. We administered ANG 1–7 (0.5 mg·kg−1·day−1) or saline to 5-mo-old db/db mice for 28 days via implanted micro-osmotic pumps. ANG 1–7 treatment reduced kidney weight and ameliorated mesangial expansion and increased urinary albumin excretion, characteristic features of diabetic nephropathy, in db/db mice. ANG 1–7 decreased renal fibrosis in db/db mice, which correlated with dephosphorylation of the signal transducer and activator of transcription 3 (STAT3) pathway. ANG 1–7 treatment also suppressed the production of reactive oxygen species via attenuation of NADPH oxidase activity and reduced inflammation in perirenal adipose tissue. Furthermore, ANG 1–7 treatment decreased lipid accumulation in db/db kidneys, accompanied by increased expressions of renal adipose triglyceride lipase (ATGL). Alterations in ATGL expression correlated with increased SIRT1 expression and deacetylation of FOXO1. The upregulation of angiotensin-converting enzyme 2 levels in diabetic nephropathy was normalized by ANG 1–7. ANG 1–7 treatment exerts renoprotective effects on diabetic nephropathy, associated with reduction of oxidative stress, inflammation, fibrosis, and lipotoxicity. ANG 1–7 can represent a promising therapy for diabetic nephropathy.

ACE2 as therapeutic agent

2020 ◽  
Vol 134 (19) ◽  
pp. 2581-2595
Author(s):  
Qiuhong Li ◽  
Maria B. Grant ◽  
Elaine M. Richards ◽  
Mohan K. Raizada
Keyword(s):  
Therapeutic Agent ◽  
Renin Angiotensin System ◽  
Peptide Hormone ◽  
Experimental Models ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
Overwhelming Evidence ◽  
Future Challenges

Abstract The angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin–angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein–coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.

scholarly journals Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors

2020 ◽  
Vol 9 (11) ◽  
pp. 3472 ◽  
Author(s):  
Elena-Mihaela Cordeanu ◽  
Lucas Jambert ◽  
Francois Severac ◽  
Hélène Lambach ◽  
Jonathan Tousch ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Severe Pneumonia ◽  
University Hospital ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Previously Treated ◽  
The Impact ◽  
Harmful Effects ◽  
Observation Period

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin–angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56–79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, “RASi” (n = 282) and “RASi-free” (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57–1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73–1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

scholarly journals In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone
Keyword(s):  
Inflammatory Markers ◽  
In Vitro Study ◽  
Inos Expression ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

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