Redox Homeostasis Alteration Is Restored through Melatonin Treatment in COVID-19 Patients: A Preliminary Study.

Type II pneumocytes are the target of the SARS-CoV-2 virus, which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. In this study, we evaluated whether treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), lipid peroxidation (LPO), and thiol groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There were significant increases in LPO and carbonyl quantities (p ≤ 0.03) and decreases in TAC and the quantities of NO2-, thiols, and GSH (p < 0.001) in COVID-19 patients. The activities of the antioxidant enzymes such as ecSOD, TrxR, GPx, GST, GR, and peroxidases were decreased (p ≤ 0.04) after the MT treatment. The treatment with MT favored the activity of the antioxidant enzymes that contributed to an increase in TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis, functioning as a glycolytic agent, and inhibited the Warburg effect. Thus, MT restores the redox homeostasis that is altered in COVID-19 patients and can be used as adjuvant therapy in SARS-CoV-2 infection.

Frailty and the Interactions between Skeletal Muscle, Bone, and Adipose Tissue-Impact on Cardiovascular Disease and Possible Therapeutic Measures.

Frailty is a global health problem that impacts clinical practice. It is complex, having a physical and a cognitive component, and it is the result of many contributing factors. Frail patients have oxidative stress and elevated proinflammatory cytokines. Frailty impairs many systems and results in a reduced physiological reserve and increased vulnerability to stress. It is related to aging and to cardiovascular diseases (CVD). There are few studies on the genetic factors of frailty, but epigenetic clocks determine age and frailty. In contrast, there is genetic overlap of frailty with cardiovascular disease and its risk factors. Frailty is not yet considered a risk factor for CVD. It is accompanied by a loss and/or poor functioning of muscle mass, which depends on fiber protein content, resulting from the balance between protein breakdown and synthesis. Bone fragility is also implied, and there is a crosstalk between adipocytes, myocytes, and bone. The identification and assessment of frailty is difficult, without there being a standard instrument to identify or treat it. Measures to prevent its progression include exercises, as well as supplementing the diet with vitamin D and K, calcium, and testosterone. In conclusion, more research is needed to better understand frailty and to avoid complications in CVD.

Reduced Levels of Selenium and Thioredoxin Reductase in the Thoracic Aorta Could Contribute to Aneurysm Formation in Patients with Marfan Syndrome.

Marfan syndrome (MFS) is an autosomal dominant disorder caused by a heterozygous mutation of the FBN1 gene. MFS patients present oxidative stress that disturbs redox homeostasis. Redox homeostasis depends in part on the enzymatic antioxidant system, which includes thioredoxin reductase (TrxR) and glutathione peroxidases (GPx), both of which require an adequate concentration of selenium (Se). Therefore, the aim of this study was to determine if Se levels are decreased in the TAA of patients with MFS since this could contribute to the formation of an aneurysm in these patients. The results show that interleukins IL-1ß, IL-6 TGF-ß1, and TNF-α (p ≤ 0.03), and carbonylation (p ≤ 0.03) were increased in the TAA of patients with MFS in comparison with control subjects, while Se, thiols (p = 0.02), TrxR, and GPx (p ≤ 0.001) were decreased. TLR4 and NOX1 (p ≤ 0.03), MMP9 and MMP2 (p = 0.04) and NOS2 (p < 0.001) were also increased. Therefore, Se concentrations are decreased in the TAA of MFS, which can contribute to a decrease in the activities of TrxR and GPx, and thiol groups. A decrease in the activities of these enzymes can lead to the loss of redox homeostasis, which can, in turn, lead to an increase in the pro-inflammatory interleukins associated with the overexpression of MMP9 and MMP2.

Effect of Hibiscus sabdariffa L. on the Metabolism of Arachidonic Acid in the Isolated Kidney of a Rat Model of Metabolic Syndrome.

The renal system is engaged in metabolic syndrome (MS) and metabolites of arachidonic acid (AA) participate in renal homeostasis and disruption of functionality. Hibiscus sabdariffa L (HSL) is used as a diuretic and could improve renal function. The aim of this study was to assess if treatment with HSL at 2% improves renal function in MS through the metabolites of AA. A total of 24 male Wistar rats were divided into four groups: Group 1, control (C); Group 2, MS with 30% sucrose in drinking water, Group 3, MS plus HSL infusion at 2% (MS+HSL); and Group 4, C+HSL. We evaluated the perfusion pressure changes (∆-PP), the activities of cyclooxygenases (COXs), the percentage of AA, the expressions of PLA2, COX2, COX1, 5-LOX, TAXS and CYP450, and the concentrations of prostaglandins in the kidney from rats with MS. There was a decrease in the ∆-PP, in the activities of COXs, and the expressions of COX2 and CYP450 (p ≤ 0.03, respectively)as well asPGE2, TxB2, and LKB4 (p ≤ 0.01, respectively). However, the percentage of AA and expressions of PLA2 and PGE1 (p = 0.01, respectively) were increased in C and MS+HSL. The HSL treatment improved the function and anatomical structure of the kidneys in the MS rats, through antioxidant molecules, and inhibited the pathways that metabolize the AA including that of PLA2, COX2, 5-LOX, TAXS, and CYP450 while favoring the COX1 pathway. This improves the vascular resistance of renal arterioles.

Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects.

Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1ß, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFß), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.

Impact on the Clinical Evolution of Patients with COVID-19 Pneumonia and the Participation of the NFE2L2/KEAP1 Polymorphisms in Regulating SARS-CoV-2 Infection.

In patients with severe pneumonia due to COVID-19, the deregulation of oxidative stress is present. Nuclear erythroid factor 2 (NRF2) is regulated by KEAP1, and NRF2 regulates the expression of genes such as NFE2L2-KEAP1, which are involved in cellular defense against oxidative stress. In this study, we analyzed the participation of the polymorphisms of NFE2L2 and KEAP1 genes in the mechanisms of damage in lung disease patients with SARS-CoV-2 infection. Patients with COVID-19 and a control group were included. Organ dysfunction was evaluated using SOFA. SARS-CoV-2 infection was confirmed and classified as moderate or severe by ventilatory status and by the Berlin criteria for acute respiratory distress syndrome. SNPs in the gene locus for NFE2L2, rs2364723C>G, and KEAP1, rs9676881A>G, and rs34197572C>T were determined by qPCR. We analyzed 110 individuals with SARS-CoV-2 infection: 51 with severe evolution and 59 with moderate evolution. We also analyzed 111 controls. Significant differences were found for rs2364723 allele G in severe cases vs. controls (p = 0.02); for the rs9676881 allele G in moderate cases vs. controls (p = 0.04); for the rs34197572 allele T in severe cases vs. controls (p = 0.001); and in severe vs. moderate cases (p = 0.004). Our results showed that NFE2L2 rs2364723C>G allele G had a protective effect against severe COVID-19, while KEAP1 rs9676881A>G allele G and rs34197572C>T minor allele T were associated with more aggressive stages of COVID-19.

Deodorized Garlic Decreases Oxidative Stress Caused by Lipopolysaccharide in Rat Heart through Hydrogen Sulfide: Preliminary Findings.

Deodorized garlic (DG) may favor the activity of the antioxidant enzymes and promote the synthesis of hydrogen sulfide (H2S). The objective was to test if DG favors an increase in H2S and if it decreases the oxidative stress caused by lipopolysaccharide (LPS) in rat hearts. A total of 24 rats were divided into 4 groups: Group 1 control (C), Group 2 LPS, Group 3 DG, and Group 4 LPS plus DG. The cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and oxidative stress markers, such as total antioxidant capacity (TAC), glutathione (GSH), selenium (Se), lipid peroxidation (LPO), thiols, hydrogen sulfide (H2S), and the activities and expressions of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), cystathionine synthetase (CBS), cystathionine γ-lyase (CTH), iNOS, and eNOS-p, were analyzed in the heart. Infarct zones in the cardiac tissue were present (p = 0.01). The CMP and CVR decreased and increased (p ≤ 0.05), TAC, GSH, H2S, NO, thiols, and GST activity (p ≤ 0.01) decreased, and LPO and iNOS increased (p ≤ 0.05). The activities and expressions of TrxR, GPx, eNOS-p, CTH, and CBS (p ≤ 0.05) decreased with the LPS treatment; however, DG normalized this effect. DG treatment decreases heart damage caused by LPS through the cross-talk between the H2S and NO systems.

Oxidative Stress, Plant Natural Antioxidants, and Obesity.

Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite. This review discusses the participation of oxidative stress in obesity and the important groups of compounds found in plants with antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, and isoflavones), and curcuminoids (b) carotenoids, (c) capsaicinoids and casinoids, (d) isothiocyanates, (e) catechins, and (f) vitamins. Examples are analyzed, such as resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, and garlic. The antioxidant activities of these compounds depend on their activities as reactive oxygen species (ROS) scavengers and on their capacity to prevent the activation of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), and reduce the expression of target genes, including those participating in inflammation. We conclude that natural compounds have therapeutic potential for diseases mediated by oxidative stress, particularly obesity. Controlled and well-designed clinical trials are still necessary to better know the effects of these compounds.

Modulation of Renal Function in a Metabolic Syndrome Rat Model by Antioxidants in Hibiscus sabdariffa L.

Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.

Nitrosative Stress and Its Association with Cardiometabolic Disorders.

: Reactive nitrogen species (RNS) are formed when there is an abnormal increase in the level of nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) and/or by the uncoupled endothelial nitric oxide synthase (eNOS). The presence of high concentrations of superoxide anions (O2-) is also necessary for their formation. RNS react three times faster than O2- with other molecules and have a longer mean half life. They cause irreversible damage to cell membranes, proteins, mitochondria, the endoplasmic reticulum, nucleic acids and enzymes, altering their activity and leading to necrosis and to cell death. Although nitrogen species are important in the redox imbalance, this review focuses on the alterations caused by the RNS in the cellular redox system that are associated with cardiometabolic diseases. Currently, nitrosative stress (NSS) is implied in the pathogenesis of many diseases. The mechanisms that produce damage remain poorly understood. In this paper, we summarize the current knowledge on the participation of NSS in the pathology of cardiometabolic diseases and their possible mechanisms of action. This information might be useful for the future proposal of anti-NSS therapies for cardiometabolic diseases.

Is Antioxidant Therapy a Useful Complementary Measure for Covid-19 Treatment? An Algorithm for Its Application.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the corona virus disease-19 which is accompanied by severe pneumonia, pulmonary alveolar collapses and which stops oxygen exchange. Viral transmissibility and pathogenesis depend on recognition by a receptor in the host, protease cleavage of the host membrane and fusion. SARS-CoV-2 binds to the angiotensin converting enzyme 2 receptor. Here, we discuss the general characteristics of the virus, its mechanism of action and the way in which the mechanism correlates with the comorbidities that increase the death rate. We also discuss the currently proposed therapeutic measures and propose the use of antioxidant drugs to help patients infected with the SARS-CoV-2. Oxidizing agents come from phagocytic leukocytes such as neutrophils, monocytes, macrophages and eosinophils that invade tissue. Free radicals promote cytotoxicity thus injuring cells. They also trigger the mechanism of inflammation by mediating the activation of NFkB and inducing the transcription of cytokine production genes. Release of cytokines enhances the inflammatory response. Oxidative stress is elevated during critical illnesses and contributes to organ failure. In corona virus disease-19 there is an intense inflammatory response known as a cytokine storm that could be mediated by oxidative stress. Although antioxidant therapy has not been tested in corona virus disease-19, the consequences of antioxidant therapy in sepsis, acute respiratory distress syndrome and acute lung injury are known. It improves oxygenation rates, glutathione levels and strengthens the immune response. It reduces mechanical ventilation time, the length of stay in the intensive care unit, multiple organ dysfunctions and the length of stay in the hospital and mortality rates in acute lung injury/acute respiratory distress syndrome and could thus help patients with corona virus disease-19.

Usefulness of Antioxidants as Adjuvant Therapy for Septic Shock: A Randomized Clinical Trial.

Background and objectives: Oxidative stress (OS) participates in the pathophysiology of septic shock, which leads to multiple organ failure (MOF), ischemia-reperfusion injury, and acute respiratory distress syndrome. Therefore, antioxidants have been proposed as therapy. Here, we evaluated the effect of antioxidant treatments in patients with septic shock with MOF and determined levels OS before and after treatment. This study was a randomized, controlled, triple-masked, and with parallel assignment clinical trial with a control group without treatment. Materials and Methods: It included 97 patients of either sex with septic shock. 5 treatments were used each in an independent group of 18 patients. Group 1 received vitamin C (Vit C), group 2 vitamin E (Vit E), group 3 n-acetylcysteine (NAC), group 4 melatonin (MT), and group 5 served as control. All antioxidants were administered orally or through a nasogastric tube for five days as an adjuvant to the standard therapy. Results: The results showed that all patients presented MOF due to sepsis upon admission and that the treatment decreased it (p = 0.007). The antioxidant treatment with NAC increased the total antioxidant capacity (p < 0.05). The patients that received Vit C had decreased levels of the nitrate and nitrite ratio (p < 0.01) and C-reactive protein levels (p = 0.04). Procalcitonin levels were reduced by Vit E (p = 0.04), NAC (p = 0.001), and MT (p = 0.04). Lipid-peroxidation was reduced in patients that received MT (p = 0.04). Conclusions: In conclusion, antioxidant therapy associated with standard therapy reduces MOF, OS, and inflammation in patients with septic shock.

Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats.

Mixtures of resveratrol (RSV) + quercetin (QRC) have antioxidant properties that probably impact on fatty liver in metabolic syndrome (MS) individuals. Here, we study the effects of a mixture of RSV + QRC on oxidative stress (OS) and fatty liver in a rat model of MS. Weanling male Wistar rats were separated into four groups (n = 8): MS rats with 30% sucrose in drinking water plus RSV + QRC (50 and 0.95 mg/kg/day, respectively), MS rats without treatment, control rats (C), and C rats plus RSV + QRC. MS rats had increased systolic blood pressure, triglycerides, insulin levels, insulin resistance index homeostasis model (HOMA), adiponectin, and leptin. The RSV + QRC mixture compensated these variables to C values (p < 0.01) in MS rats. Lipid peroxidation and carbonylation were increased in MS. Total antioxidant capacity and glutathione (GSH) were decreased in MS and compensated in MS plus RVS + QRC rats. Catalase, superoxide dismutase isoforms, peroxidases, glutathione-S-transferase, glutathione reductase, and the expression of Nrf2 were decreased in MS and reversed in MS plus RVS + QRC rats (p < 0.01). In conclusion, the mixture of RSV + QRC has benefic effects on OS in fatty liver in the MS rats through the improvement of the antioxidant capacity and by the over-expression of the master factor Nrf2, which increases the antioxidant enzymes and GSH recycling.

Sebaceous gland carcinoma and mammary gland carcinoma in an African hedgehog (Ateletrix albiventris).

A sebaceous carcinoma was diagnosed, together with a mammary carcinoma, in an adult African hedgehog (Atelerix albiventris). The first neoplasm was located in the subcutaneous tissue of the neck and extended towards the axillary area of the chest. The second was located in the subcutaneous left caudal abdominal region. The purpose of this paper is to report the histopathologic and ultrastructural features of these neoplasms. Although there is little information about diseases affecting this species, it is known that neoplastic disorders are fairly common in African hedgehogs. The mammary carcinoma is considered to be the most common neoplasm in these animals; however, the presentation of sebaceous carcinoma is rare. In hedgehogs, the simultaneous presence of two neoplasms is common, which is why special attention should be paid to the presentation of other tumors during the early detection of a neoplastic process as this will greatly facilitate the optimal treatment and improve the long-term prognosis of affected animals.

The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders.

Marfan syndrome (MFS) is a multisystem genetic disorder with over 3000 mutations described in the fibrillin 1 (FBN1) gene. Like MFS, other connective tissue disorders also require a deeper understanding of the phenotype-genotype relationship due to the complexity of the clinical presentation, where diagnostic criteria often overlap. Our objective was to identify mutations in patients with connective tissue disorders using a genetic multipanel and to analyze the genotype-phenotype associations in a cohort of Mexican patients. We recruited 136 patients with MFS and related syndromes from the National Institute of Cardiology. Mutations were identified using next-generation sequencing (NGS). To examine the correlation between mutation severity and severe cardiovascular conditions, we focused on patients who had undergone Bentall-de Bono surgery or aortic valve repair. The genetic data obtained allowed us to reclassify the initial clinical diagnosis across various types of connective tissue disorders. The transforming growth factor beta receptor 2 (TGFBR2) rs79375991 mutation was found in 10 out of 16 (63%) Loeys-Dietz patients. We observed a high prevalence (65%) of more severe mutations, such as frameshift indels and stop codons, among patients requiring invasive treatments like aortic valve-sparing surgery, Bentall and de Bono procedures, or aortic valve replacement due to severe cardiovascular injury. Although our study did not achieve precise phenotype-genotype correlations, it underscores the importance of a multigenetic panel evaluation. This could pave the way for a more comprehensive diagnostic approach and inform medical and surgical treatment decision-making.

Alteration of the aortic vascular reactivity associated to excessive consumption of Hibiscus sabdariffa Linnaeus: Preliminary findings.

The moderate production of reactive oxidative species (ROS) is important because ROS act as second messengers. However, their depletion through the over-activity of the antioxidant system may lead to reductive stress (RS) which is characterized by an increase in reducing equivalents and an elevation of some components of the antioxidant system disturbing redox homeostasis. Hibiscus sabdariffa Linnaeus (HSL) is a plant with antioxidant properties that provides compounds that favor the antioxidant system. However, excess chronic consumption could lead to the over expression of the antioxidant enzymatic system, and this could contribute to decrease ROS. Therefore, the objective of this study was to evaluate the alteration of the vascular reactivity associated to excessive and chronic consumption of HSL infusions at different percentages. 40 male Wistar rats were divided into 4 groups. Group 1 control (drinking tap water), group 2, 3 and 4, drinking water supplemented with 15, 30 and 60 g/L of HSL calyxes respectively. The systolic blood pressure (SBP), vascular reactivity, morphological changes, and different components of the enzymatic antioxidant system were evaluated in the thoracic aorta by spectrophotometry. We also determined glucose-6-phosphate dehydrogenase (G6PD), glutathione-S-transferase (GST), thioredoxin-reductase (TrxR), glutathione peroxidase (GPx) and glutathione reductase (GR) and some markers of the non-enzimatic system such as the NO3-/NO2-ratio, glutathione (GSH), selenium, thiols, lipoperoxidation (LPO), and 3-nitrityrosine (3-NT). Vasoconstriction was increased and vasorelaxation was decreased. These alterations were reversed by O2- and H2O2. There was an increase in the wall thickness and elastic fibers (p = 0.004 and p = 0.02, respectively) and in G6PD, GPX, TrxR (p = 0.02, p = 0.03, and p = 0.01 respectively). LPO, GSH (p = 0.01), and selenium (p = 0.04) were decreased. There was a decrease in thiols (p < 0.001), 3-NT (p = 0.04) and GST (p = 0.0005) in rats that received the infusion at 3 and 6%. The excess antioxidants provided by the HSL infusions at 3% and 6% modified vascular reactivity, increasing the enzymatic antioxidant system, and depleting ROS.

N-Acetyl Cysteine Restores the Diminished Activity of the Antioxidant Enzymatic System Caused by SARS-CoV-2 Infection: Preliminary Findings.

SARS-CoV-2 infects type II pneumocytes and disrupts redox homeostasis by overproducing reactive oxygen species (ROS). N-acetyl cysteine (NAC) is a precursor of the synthesis of glutathione (GSH) and it restores the loss of redox homeostasis associated to viral infections. The aim of the study is to evaluate the effect of the treatment with NAC on the enzymatic antioxidant system in serum from patients infected by SARS-CoV-2. We evaluated the enzymatic activities of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), -S-transferase (GST), and reductase (GR) by spectrophotometry and the concentrations of the glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), and lipid peroxidation (LPO) in serum. The activity of the extracellular super oxide dismutase (ecSOD) was determined by native polyacrylamide gels, and 3-nitrotyrosine (3-NT) was measured by ELISA. A decrease in the activities of the ecSOD, TrxR, GPx, GST GR, (p = 0 ≤ 0.1), and the GSH, TAC, thiols, and NO2- (p ≤ 0.001) concentrations and an increase in LPO and 3-NT (p = 0.001) concentrations were found in COVID-19 patients vs. healthy subjects. The treatment with NAC as an adjuvant therapy may contribute to a reduction in the OS associated to the infection by SARS-CoV-2 through the generation of GSH. GSH promotes the metabolic pathways that depend on it, thus contributing to an increase in TAC and to restore redox homeostasis.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

The Possible Role of Glucose-6-Phosphate Dehydrogenase in the SARS-CoV-2 Infection.

Glucose-6-phosphate dehydrogenase (G6PD) is the second rate-limiting enzyme of the pentose phosphate pathway. This enzyme is present in the cytoplasm of all mammalian cells, and its activity is essential for an adequate functioning of the antioxidant system and for the response of innate immunity. It is responsible for the production of nicotinamide adenine dinucleotide phosphate (NADPH), the first redox equivalent, in the pentose phosphate pathway. Viral infections such as SARS-CoV-2 may induce the Warburg effect with an increase in anaerobic glycolysis and production of lactate. This condition ensures the success of viral replication and production of the virion. Therefore, the activity of G6PD may be increased in COVID-19 patients raising the level of the NADPH, which is needed for the enzymatic and non-enzymatic antioxidant systems that counteract the oxidative stress caused by the cytokine storm. G6PD deficiency affects approximately 350-400 million people worldwide; therefore, it is one of the most prevalent diseases related to enzymatic deficiency worldwide. In G6PD-deficient patients exposed to SARS-CoV-2, the amount of NADPH is reduced, increasing the susceptibility for viral infection. There is loss of the redox homeostasis in them, resulting in severe pneumonia and fatal outcomes.

Interconnection between Cardiac Cachexia and Heart Failure-Protective Role of Cardiac Obesity.

Cachexia may be caused by congestive heart failure, and it is then called cardiac cachexia, which leads to increased morbidity and mortality. Cardiac cachexia also worsens skeletal muscle degradation. Cardiac cachexia is the loss of edema-free muscle mass with or without affecting fat tissue. It is mainly caused by a loss of balance between protein synthesis and degradation, or it may result from intestinal malabsorption. The loss of balance in protein synthesis and degradation may be the consequence of altered endocrine mediators such as insulin, insulin-like growth factor 1, leptin, ghrelin, melanocortin, growth hormone and neuropeptide Y. In contrast to many other health problems, fat accumulation in the heart is protective in this condition. Fat in the heart can be divided into epicardial, myocardial and cardiac steatosis. In this review, we describe and discuss these topics, pointing out the interconnection between heart failure and cardiac cachexia and the protective role of cardiac obesity. We also set the basis for possible screening methods that may allow for a timely diagnosis of cardiac cachexia, since there is still no cure for this condition. Several therapeutic procedures are discussed including exercise, nutritional proposals, myostatin antibodies, ghrelin, anabolic steroids, anti-inflammatory substances, beta-adrenergic agonists, medroxyprogesterone acetate, megestrol acetate, cannabinoids, statins, thalidomide, proteasome inhibitors and pentoxifylline. However, to this date, there is no cure for cachexia.