Role of oxidative stress in the severity of SARS-COV-2 infection

Since the World Health Organization declared SARS-CoV-2 (COVID-19) a pandemic in March 2020, serious efforts have been made to understand the epidemiology, molecular mechanisms, pathology, and clinical evolution of this disease. Oxidative stress (OX-S) has been implicated in the etiologies of many diseases, including SARS-CoV-2. Recent studies suggest that superoxide radicals and the products of lipid peroxidation, such as the electrophilic aldehyde, 4-hydroxynonenal (4-HNE), are important mediators of the pathological effects of oxidative stress during microbial and viral infections. Numerous studies have confirmed that viral infections induce inflammatory responses that generate excessive amounts of reactive oxygen species and 4-HNE protein adducts in plasma and in various tissues, including alveolar epithelium and endothelium. In this book chapter, we will highlight and discuss the apparent and plausible relationships between SARS-CoV-2 virulence and oxidative stress/lipid peroxidation, which affect cellular and DNA repair mechanisms and immune response. © 2023 Elsevier Inc. All rights reserved.

Effect of Vaccination on Platelet Mitochondrial Bioenergy Function of Patients with Post-Acute COVID-19.

BACKGROUND: Mitochondrial dysfunction and redox cellular imbalance indicate crucial function in COVID-19 pathogenesis. Since 11 March 2020, a global pandemic, health crisis and economic disruption has been caused by SARS-CoV-2 virus. Vaccination is considered one of the most effective strategies for preventing viral infection. We tested the hypothesis that preventive vaccination affects the reduced bioenergetics of platelet mitochondria and the biosynthesis of endogenous coenzyme Q10 (CoQ10) in patients with post-acute COVID-19. MATERIAL AND METHODS: 10 vaccinated patients with post-acute COVID-19 (V + PAC19) and 10 unvaccinated patients with post-acute COVID-19 (PAC19) were included in the study. The control group (C) consisted of 16 healthy volunteers. Platelet mitochondrial bioenergy function was determined with HRR method. CoQ10, γ-tocopherol, α-tocopherol and ß-carotene were determined by HPLC, TBARS (thiobarbituric acid reactive substances) were determined spectrophotometrically. RESULTS: Vaccination protected platelet mitochondrial bioenergy function but not endogenous CoQ10 levels, in patients with post-acute COVID-19. CONCLUSIONS: Vaccination against SARS-CoV-2 virus infection prevented the reduction of platelet mitochondrial respiration and energy production. The mechanism of suppression of CoQ10 levels by SARS-CoV-2 virus is not fully known. Methods for the determination of CoQ10 and HRR can be used for monitoring of mitochondrial bioenergetics and targeted therapy of patients with post-acute COVID-19.

Assessment of Antioxidant, Anti-Lipid Peroxidation, Antiglycation, Anti-Inflammatory and Anti-Tyrosinase Properties of Dendrobium sulcatum Lindl

Dendrobium sulcatum Lindl or "Ueang Jampa-Nan” (Orchidaceae family) is widely dis-tributed in Thailand and Laos. It is classified in the genus Dendrobium, which is used in both traditional Chinese medicine and Ayurvedic medicine for health enhancement and anti-aging. The purpose of this study was to investigate the phytochemical constituents and bioefficacy of stems, leaves and flowers from D. sulcatum for cosmetic and cosmeceutical applications. Phenolic and flavonoid contents were tested for the phytochemical evaluation. The antioxidant (DPPH, FRAP and ABTS assays), anti-lipid peroxidation, antiglycation, anti-inflammatory and anti-tyrosinase properties were assessed for their bioefficacy. The results showed that the extracts of stem and leaf had higher total phenolic content than that of the flower, and the leaf extract had the highest flavonoid content. The antioxidant, anti-lipid peroxidation and anti-inflammatory activities of the extracts were greater in those from the stem and leaf compared with that of the flower. The leaf extract exhibited the greatest antiglycation property. The results of anti-tyrosinase analysis of the extracts showed that the leaf and flower exhibited potent activities with a percentage inhibition greater than 70% (at a concentration of 50 µg/mL). In conclusion, these findings suggest that the ethanolic extracts from different parts of D. sulcatum are promising sources of natural active ingredients for further cosmetic and cosmeceutical products.

Tracheotomy In Patients With Covid-19

Relevance. The coronavirus rush, which has appeared since December 2019, has an impact on economic, medical, and social development in all countries of the world. There are still no standard diagnostic and therapeutic plans aimed at limiting this infection. Purpose. To determine the therapeutic role of tracheostomy with patients with coronavirus infection. Material. The prospective study of 100 patients with coronavirus infection was carried out on the basis of State Budgetary Healthcare Institution "Interdistrict Multidisciplinary Hospital" in Nartkala city. When patients were admitted to the clinic, they were randomized into 2 groups depending on the therapy: the first group (comparison, n=50) - patients received traditional therapy in intensive care;the second (main, n=50) group - patients underwent tracheostomy in addition to standard therapy. The average age was 56.2+/-4.8 years. The women's average age was 55 years (55.0%), and the men's - 45 years (45.0%). Methods. Determination of the syndrome of endogenous intoxication, taxation of lipid peroxidation intensification. The local microcirculation was investigated by the apparatus LAKK-02. The activity of the coagulation-lytic blood system was found by thrombelastograph TEG 5000. Results. Early COVID-19 infection demonstrates signs of intoxication, oxidative depression, phospholipase activity, microcirculatory and hemostatic disorders. These changes were the cause of the development of life-threatening complications (neurological, pulmonary, cardiac, etc.). They were associated with the type of treatment. Traditional treatment and the use of mask oxygen turned out to be ineffective, since the homeostasis system disorders remained throughout the investigation period. The inclusion of tracheostomy in traditional therapy makes it possible to quickly improve the course of pathology as it purposefully affects the pathogenetic links of the homeostasis system. Conclusion. The use of tracheostomy in the scheme of standard treatment of coronavirus infection allows improving the effectiveness of general therapy of COVID-19 patients, especially with severe forms.Copyright © 2023, Codon Publications. All rights reserved.

The Potential Impact of Ayurvedic Traditional Bhasma on SARS-CoV-2-Induced Pathogenesis

The mass casualties caused by the delta variant and the wave of the newer "Omicron" variant of SARS-COV-2 in India have brought about great concern among healthcare officials. The government and healthcare agencies are seeking effective strategies to counter the pandemic. The application of nanotechnology and repurposing of drugs are reported as promising approaches in the management of COVID-19 disease. It has also immensely boomed the search for productive, re-liable, cost-effective, and bio-assimilable alternative solutions. Since ancient times, the traditional-ly employed Ayurvedic bhasmas have been used for diverse infectious diseases, which are now employed as nanomedicine that could be applied for managing COVID-19-related health anomalies. Like currently engineered metal nanoparticles (NPs), the bhasma nanoparticles (BNPs) are also packed with unique physicochemical properties, including multi-elemental nanocrystalline compo-sition, size, shape, dissolution, surface charge, hydrophobicity, and multi-pathway regulatory as well as modulatory effects. Because of these conformational and configurational-based physico-chemical advantages, Bhasma NPs may have promising potential to manage the COVID-19 pandemic and reduce the incidence of pneumonia-like common lung infections in children as well as age-related inflammatory diseases via immunomodulatory, anti-inflammatory, antiviral, and adju-vant-related properties.Copyright © 2023 Bentham Science Publishers.

To estimate oxidative stress and DNA damage in postCOVID patients

Title: To estimate oxidative stress and DNA damage in Post COVID patients. Background There are a subset of COVID-19 patients who develop sequelae to the disease and oxidative stress is a less studied factor in the development of the sequelae. Aims and Objectives: We have estimated levels of lipid peroxidation (LPO) via malondialdehyde assay kit and DNA damage via alkaline comet assay in hospitalized post-COVID patients symptomatic 4 weeks after testing RT-PCR positive and studied their clinical radiological correlation as a means of estimating the oxidative stress in them. Method(s): It was a single-center, hospital-based comparative case-control pilot study in which 40 post-COVID-19 patients and 40 healthy controls were enrolled. The residual symptoms and baseline clinical and radiological profile of the subjects were also assessed and lipid peroxidation and DNA comet analysis were performed in the blood samples of patients and controls. Result(s): Mean value of LPO was increased (1155.9 +/- 204.82 nmol/ml) in post COVID subjects as compared to controls (715.5 +/- 85.51nmole/ml (P=0.0405). Values were directly proportional to the Severity of COVID (P=0.0317) and X-ray severity score(P=0.009) and were found higher in patients with comorbidities (P=0.0320) and multisystem involvement specifically in those developing a neurological sequela (P=0.0083). Damaged DNA tails and the tailing is directly proportional to DNA damage. The comet parameters measured in our study were Tail length, Tail DNA (%), and Olive tail moment. All these comet parameters were found elevated in Post COVID subjects as compared with healthy controls. Conclusion(s): Oxidative stress and DNA damage, has a role in the development of post-COVID sequelae as seen by high levels of LPO and tail DNA in these subjects.

Transcriptional Insights of Oxidative Stress and Extracellular Traps in Lung Tissues of Fatal COVID-19 Cases.

Neutrophil extracellular traps (NETs) and oxidative stress are considered to be beneficial in the innate immune defense against pathogens. However, defective clearance of NETs in the lung of acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients could lead to severe respiratory syndrome infection, the so-called coronavirus disease 2019 (COVID-19). To elucidate the pathways that are related to NETs within the pathophysiology of COVID-19, we utilized RNA sequencing (RNA-seq) as well as immunofluorescence and immunohistochemistry methods. RNA-seq analysis provided evidence for increased oxidative stress and the activation of viral-related signaling pathways in post-mortem lungs of COVID-19 patients compared to control donors. Moreover, an excess of neutrophil infiltration and NET formation were detected in the patients' lungs, where the extracellular DNA was oxidized and co-localized with neutrophil granule protein myeloperoxidase (MPO). Interestingly, staining of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) depicted high colocalization with NETs and was correlated with the neutrophil infiltration of the lung tissues, suggesting that it could serve as a suitable marker for the identification of NETs and the severity of the disease. Moreover, local inhalation therapy to reduce the excess lipid oxidation and NETs in the lungs of severely infected patients might be useful to ameliorate their clinical conditions.

COVID-19 Causes Ferroptosis and Oxidative Stress in Human Endothelial Cells.

Oxidative stress and endothelial dysfunction have been shown to play crucial roles in the pathophysiology of COVID-19 (coronavirus disease 2019). On these grounds, we sought to investigate the impact of COVID-19 on lipid peroxidation and ferroptosis in human endothelial cells. We hypothesized that oxidative stress and lipid peroxidation induced by COVID-19 in endothelial cells could be linked to the disease outcome. Thus, we collected serum from COVID-19 patients on hospital admission, and we incubated these sera with human endothelial cells, comparing the effects on the generation of reactive oxygen species (ROS) and lipid peroxidation between patients who survived and patients who did not survive. We found that the serum from non-survivors significantly increased lipid peroxidation. Moreover, serum from non-survivors markedly regulated the expression levels of the main markers of ferroptosis, including GPX4, SLC7A11, FTH1, and SAT1, a response that was rescued by silencing TNFR1 on endothelial cells. Taken together, our data indicate that serum from patients who did not survive COVID-19 triggers lipid peroxidation in human endothelial cells.

Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

Evaluation of Total Antioxidant Capacity and Total Oxidant Status in Patients with COVID-19

The COVID-19 is spreading rapidly over the globe disease . A deadly global pandemic of Coronavirus sickness (COVID-19) has caused significant morbidity and mortality in a number of locations. Oxidative stress appears to play a role in COVID-19. The goal of this case-control study was to compare the levels of total antioxidant capacity (TAC), total oxidant status (TOS), and lipid peroxidation products like malondialdehyde (MDA) in the serum of COVID-19 infection patients to a healthy control group, with a scientific interpretation of the results. The data was gathered from (90) participants who were classified into two categories: patients and controls. The CUPRAC procedure evaluates A spectrophotometric reader was used to determine the total oxidant status (TOS). With a p-value of 0.05, the results revealed that there were significant variations in TOS levels between the COVID -19 and control groups (0.009). TAC levels differed significantly between the patient and control groups, with a p-value of (0.012), while TAC levels in the patient group dropped. (1.24+/-0.15), compared to (1.55+/-0.31) in the control group;moreover, oxidative stress is higher in covid-19, with MDA levels of (6.45+/-1.14), compared to (3.22+/-0.69) in the control group, with a significant p-value (0.002). Conclusion(s): Based on the data, it seems that levels of (MDA) are higher in the COVID-19 group than in the control group due to Infection with a virus and a storm of the immune system In addition to acting as an anti-inflammatory mediator, (MDA) is a biomarker for lipid peroxidation, and an increase in free radicals causes oxidative stress, resulting in an increase in (MDA) levels. (TAC) levels were also lower in patients than in the control group, and our findings revealed that patients had higher (TOS) levels than the control group. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Nutritional and Metabolic Control of Ferroptosis.

Ferroptosis is a type of regulated cell death characterized by an excessive lipid peroxidation of cellular membranes caused by the disruption of the antioxidant defense system and/or an imbalanced cellular metabolism. Ferroptosis differentiates from other forms of regulated cell death in that several metabolic pathways and nutritional aspects, including endogenous antioxidants (such as coenzyme Q10, vitamin E, and di/tetrahydrobiopterin), iron handling, energy sensing, selenium utilization, amino acids, and fatty acids, directly regulate the cells' sensitivity to lipid peroxidation and ferroptosis. As hallmarks of ferroptosis have been documented in a variety of diseases, including neurodegeneration, acute organ injury, and therapy-resistant tumors, the modulation of ferroptosis using pharmacological tools or by metabolic reprogramming holds great potential for the treatment of ferroptosis-associated diseases and cancer therapy. Hence, this review focuses on the regulation of ferroptosis by metabolic and nutritional cues and discusses the potential of nutritional interventions for therapy by targeting ferroptosis.

The Significance of COVID-19 Diseases in Lipid Metabolism Pregnancy Women and Newborns.

Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. Elderly people, people with immunodeficiency, autoimmune and malignant diseases, as well as people with chronic diseases have a higher risk of developing more severe forms of the disease. Pregnant women and children can becomesick, although more often they are only the carriers of the virus. Recent studies have indicated that infants can also be infected by SARS-CoV-2 and develop a severe form of the disease with a fatal outcome. Acute Respiratory Distress Syndrome (ARDS) ina pregnant woman can affect the supply of oxygen to the fetus and initiate the mechanism of metabolic disorders of the fetus and newborn caused by asphyxia. The initial metabolic response of the newborn to the lack of oxygen in the tissues is the activation of anaerobic glycolysis in the tissues and an increase in the concentration of lactate and ketones. Lipid peroxidation, especially in nerve cells, is catalyzed by iron released from hemoglobin, transferrin and ferritin, whose release is induced by tissue acidosis and free oxygen radicals. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through various pathways, resulting in a decrease in the antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in the cells, ultimately leading to oxidative cell stress, and finally, death. Conclusion: damage to the mitochondria as a result of lipid peroxidation caused by the COVID-19 disease can cause the death of a newborn and pregnant women as well as short time and long-time sequelae.

A review: The phytochemistry, pharmacology, and pharmacokinetics of Curcumae Longae Rhizoma (Turmeric)

Curcumae Longae Rhizoma (CLR) is the rhizome of Curcuma longa L. Pharmacological studies show that CLR can be used to treat cervical cancer, lung cancer, lupus nephritis, and other conditions. In this paper, we review botany, traditional application, phytochemistry, pharmacological activity, and pharmacokinetics of CLR. The literature from 1981 to date was entirely collected from online databases, such as Web of Science, Google Scholar, China Academic Journals full-text database (CNKI), Wiley, Springer, PubMed, and ScienceDirect. The data were also obtained from ancient books, theses and dissertations, and Flora Reipublicae Popularis Sinicae. There are a total of 275 compounds that have been isolated from CLR, including phenolic compounds, volatile oils, and others. The therapeutic effect of turmeric has been expanded from breaking blood and activating qi in the traditional sense to antitumor, anti-inflammatory, antioxidation, neuroprotection, antibacterial, hypolipidemic effects, and other benefits. However, the active ingredients and mechanisms of action related to relieving disease remain ill defined, which requires more in-depth research and verification at a clinical level.

Diversified Effects of COVID-19 as a Consequence of the Differential Metabolism of Phospholipids and Lipid Peroxidation Evaluated in the Plasma of Survivors and Deceased Patients upon Admission to the Hospital.

As a result of SARS-CoV-2 infection, inflammation develops, which promotes oxidative stress, leading to modification of phospholipid metabolism. Therefore, the aim of this study is to compare the effects of COVID-19 on the levels of phospholipid and free polyunsaturated fatty acids (PUFAs) and their metabolites produced in response to reactions with reactive oxygen species (ROS) and enzymes (cyclooxygenases-(COXs) and lipoxygenase-(LOX)) in the plasma of patients who either recovered or passed away within a week of hospitalization. In the plasma of COVID-19 patients, especially of the survivors, the actions of ROS and phospholipase A2 (PLA2) cause a decrease in phospholipid fatty acids level and an increase in free fatty acids (especially arachidonic acid) despite increased COXs and LOX activity. This is accompanied by an increased level in lipid peroxidation products (malondialdehyde and 8-isoprostaglandin F2α) and lipid mediators generated by enzymes. There is also an increase in eicosanoids, both pro-inflammatory as follows: thromboxane B2 and prostaglandin E2, and anti-inflammatory as follows: 15-deoxy-Δ-12,14-prostaglandin J2 and 12-hydroxyeicosatetraenoic acid, as well as endocannabinoids (anandamide-(AEA) and 2-arachidonylglycerol-(2-AG)) observed in the plasma of patients who recovered. Moreover, the expression of tumor necrosis factor α and interleukins (IL-6 and IL-10) is increased in patients who recovered. However, in the group of patients who died, elevated levels of N-oleoylethanolamine and N-palmitoylethanolamine are found. Since lipid mediators may have different functions depending on the onset of pathophysiological processes, a stronger pro-inflammatory response in patients who have recovered may be the result of the defensive response to SARS-CoV-2 in survivors associated with specific changes in the phospholipid metabolism, which could also be considered a prognostic factor.

Recent advances in molecular biology of metabolic syndrome pathophysiology: endothelial dysfunction as a potential therapeutic target.

Current advances in molecular pathobiology of endotheliocytes dysfunctions are promising in finding the pathogenetic links to the emergence of insulin resistance syndrome. Physiologically, human organism homeostasis is strictly controlled to maintain metabolic processes at the acquainted level. Many factors are involved in maintaining these physiological processes in the organism and any deviation is undoubtedly accompanied by specific pathologies related to the affected process. Fortunately, the body's defense system can solve and compensate for the impaired function through its multi-level defense mechanisms. The endothelium is essential in maintaining this homeostasis through its ability to modulate the metabolic processes of the organism. Pathological activity or impairment of physiological endothelium function seems directly correlated to the emergence of metabolic syndrome. The most accepted hypothesis is that endothelium distribution is due to endoplasmic reticulum stress and unfolded protein response development, which includes inhibition of long non-coding RNAs expression, cytokines disbalance, Apelin dysregulation, glycocalyx degradation, and specific microparticles. Clinically, the enhancement or restoration of normal endothelial cells can be a target for novel therapeutic strategies since the distribution of its physiological activity impairs homeostasis and results in the progression of metabolic syndrome, and induction of its physiological activity can ameliorate insulin resistance syndrome. Novel insights on the molecular mechanisms of endothelial cell dysfunction are concisely represented in this paper to enhance the present therapeutic tactics and advance the research forward to find new therapeutic targets.

Molecular Mechanisms of Ferroptosis and Relevance to Cardiovascular Disease.

Ferroptosis has recently been demonstrated to be a novel regulated non-apoptotic cell death characterized by iron-dependence and the accumulation of lipid peroxidation that results in membrane damage. Excessive iron induces ferroptosis by promoting the generation of both soluble and lipid ROS via an iron-dependent Fenton reaction and lipoxygenase (LOX) enzyme activity. Cytosolic glutathione peroxidase 4 (cGPX4) pairing with ferroptosis suppressor protein 1 (FSP1) and mitochondrial glutathione peroxidase 4 (mGPX4) pairing with dihydroorotate dehydrogenase (DHODH) serve as two separate defense systems to detoxify lipid peroxidation in the cytoplasmic as well as the mitochondrial membrane, thereby defending against ferroptosis in cells under normal conditions. However, disruption of these defense systems may cause ferroptosis. Emerging evidence has revealed that ferroptosis plays an essential role in the development of diverse cardiovascular diseases (CVDs), such as hemochromatosis-associated cardiomyopathy, doxorubicin-induced cardiotoxicity, ischemia/reperfusion (I/R) injury, heart failure (HF), atherosclerosis, and COVID-19-related arrhythmias. Iron chelators, antioxidants, ferroptosis inhibitors, and genetic manipulations may alleviate the aforementioned CVDs by blocking ferroptosis pathways. In conclusion, ferroptosis plays a critical role in the pathogenesis of various CVDs and suppression of cardiac ferroptosis is expected to become a potential therapeutic option. Here, we provide a comprehensive review on the molecular mechanisms involved in ferroptosis and its implications in cardiovascular disease.

The Impact of Severe COVID-19 on Plasma Antioxidants.

Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARS-CoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients.

Pharmacological activities of Curcumin: An update

In the past few years, multiple drugs have been produced from traditional raw materials and recent pandemic disease COVID-19 once again research on this matter is being conducted to determine potential therapeutic purposes of different Ayurvedic Indian medicines and herbs. One such medicinal herb is Curcuma longa. Curcumin is strong antioxidant, anti-inflammatory, antispasmodic, antiangiogenic, anti-carcinogenic, as shown by multiple in vitro and in vivo studies. The action of the growth factor receptors is inhibited by curcumin. The anti-inflammatory effect of curcumin is obtained on the cytokines, proteolytic enzymes, eicosanoids, and lipid mediators. The superoxide radicals, nitric oxide and hydrogen peroxide, are sifted by curcumin, while lipid peroxidation is inhibited. Such properties of the compound thus form the foundation for its various therapeutic and pharmacological effects could also hold antiviral properties including COVID-19. The aim of this research is to summarize the updated pharmacological activities of curcumin.

ELEVATED ROS LEVELS AND DNA FRAGMENTATION IN SPERM FROM CONVALESCENT MEN IN SARS-COV-2 INFECTION

INTRODUCTION AND OBJECTIVE: Current evidence has proven the systemic nature of COVID19, including its involvement in the male reproductive tract. We aimed to investigate seminal parameters of moderate-to-severe COVID-19 men during the convalescence phase. METHODS: This cross-sectional study included 18 to 50-yearold men with confirmed moderate-to-severe COVID-19. Patients were enrolled 15 to 45 days after the diagnosis. After a urologist's initial clinical evaluation, semen samples were obtained by masturbation and processed within one hour. Semen analysis was performed using the World Health Organization (WHO) manual (6th edition). Sperm function tests were conducted in an andrology laboratory, including Reactive oxygen species (ROS), DNA fragmentation, lipid peroxidation, and Creatine Kinase (CK) analysis. An essential endocrine evaluation was performed. Patients with a history of disorders that could impair testicular function were excluded. A group of pre-vasectomy baseline samples was used as a control group. Statistical analysis was performed using R version 4.0.5. One-tailed and paired T-tests were used for comparisons between groups. RESULTS: The sample size was 26 men (mean 34.3±6.5 years;range: 21-50 years). Sperm concentration (mean 38.74±32, P <0.01) and total motile count (mean 55.3±66.8, P <0.01) were significantly reduced in the COVID-19 group. The DNA fragmentation (mean 41.1±29.2) and ROS (mean 4.84±8.7) were significantly higher in post-infection patients. Other parameters such as WHO/ Kruger morphology and progressive motility were also reduced in the disease group, albeit not statistically significant. Total testosterone (mean 409.2±201.2) was lower in the convalescent men. All semen samples were negative for SARS-CoV-2 using the PCR analysis. CONCLUSIONS: Our findings indicate that male reproductive injury can be a relevant component of SARS-CoV-2 systemic infection. High DNA fragmentation and ROS, hallmarks of tissue injury, might signal a direct testicular involvement. The morphological and functional damage could represent significant impairment of the male reproductive health if persistent after convalescence.