Superoxide Dismutase Inhibitors against Malaria, Leishmaniasis, and Chagas Disease: Systematic Review.

INTRODUCTION: Diseases caused by protozoa are one of the leading causes of death worldwide, especially in tropical regions such as Brazil. Chagas disease, leishmaniasis, and malaria are responsible for around 234 million cases and more than 400,000 deaths worldwide. Despite this scenario, drugs for these diseases have several limitations, which justifies the search for new treatments. Iron superoxide dismutase is a promising target for the drug design to treat patients with these diseases. It is a validated target and protects against oxidative stress. AIM: Thus, this systematic review aimed to synthesize evidence on the importance of superoxide dismutase in the drug design to treat patients with this protozoosis. METHODS: A search was performed for in vitro and in vivo studies, without publication and language restrictions, in MEDLINE (PubMed), LILACS (BVS), Science Direct, and EMBASE (Elsevier). Studies that pointed to the relationship between the reduction or increase in superoxide dismutase activity and the diseases were included. 23 studies were selected for the qualitative synthesis. RESULTS: The results showed that the inhibition or reduction of the enzyme activity decreases the degree of infection and reinfection and improves the results in treating these diseases. In contrast, the increase in activity caused a high degree of survival and resistance of the parasites. CONCLUSION: However, the overall quality of evidence is low and more studies with methodological rigor are provided.

Ascorbic Acid vs Calcitriol in Influencing Monocyte Chemoattractant Protein-1, Nitric Oxide, Superoxide Dismutase, as Markers of Endothelial Dysfunction: In Vivo Study in Atherosclerosis Rat Model.

Introduction: Ascorbic acid and calcitriol were frequently utilized in conjunction as therapy during the COVID-19 pandemic, and individuals with minor symptoms had notable improvements. There have been a few studies, often with conflicting findings, that examine the use of them for endothelium restoration and numerous clinical trial studies that failed to establish the efficacy. The aim of this study was to find the efficacy of ascorbic acid compared to calcitriol on the inflammatory markers monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO), and superoxide dismutase (SOD), as protective agents which play an important role in the early stages of atherosclerosis formation. This study was an experimental in vivo study. Methods: The total of 24 male Rattus norvegicus strain Wistar rats were divided into 4 groups, namely: control/normal group (N), atherosclerosis group (DL) given atherogenic diet, atherosclerosis group given atherogenic diet and ascorbic acid (DLC), and atherosclerosis group given atherogenic diet and calcitriol (DLD) treatment for 30 days. Results: Ascorbic acid and calcitriol treatment was significantly effective (P<0.05) in lowering expression of MCP-1 and increasing NO and SOD level. Calcitriol was superior to ascorbic acid in increasing SOD (P<0.05). There was no significant difference between ascorbic acid and calcitriol in decreasing MCP-1 and increasing NO (P>0.05). Discussion: Both treatments could reduce MCP-1, and increase NO and SOD by increasing antioxidants. In this study calcitriol was superior to ascorbic acid in increasing SOD, but not NO and decreasing MCP-1. According to the theory, it was found that calcitriol through nuclear factor erythroid 2-related factor 2 (Nrf2) causes a direct increase in the amount of SOD. Nrf2 is an emerging regulator of cellular resistance to oxidants. Conclusion: Ascorbic acid and calcitriol treatment was able to reduce MCP-1 and increase NO and SOD in atherosclerosis rat. Calcitriol was significantly superior in increasing SOD levels compared to ascorbic acid.

Pro-and Antioxidant Status in Newborn with COVID-19.

There is practically no information on the state of oxidative stress reactions in newborns with coronavirus infections. At the same time, such studies are extremely important and can contribute to better understanding of the process of reactivity in patients of different ages. The content of pro- and antioxidant status indicators was assessed in 44 newborns with confirmed COVID-19. It was found that the content of compounds with unsaturated double bonds, primary, secondary, and final LPO products were elevated in newborns with COVID-19. These changes were accompanied by higher SOD activity and retinol level and reduced activity of glutathione peroxidase. Contrary to popular opinion, newborns can be a COVID-19-susceptible age group and require more close monitoring of metabolic reactions during the period of neonatal adaptation that is an aggravating background during infection.

Relationship between toxicity and oxidative stress of the nanoencapsulated colchicine in a model of Drosophila melanogaster.

Drug repurposing allows searching for new biological targets, especially against emerging diseases such as Covid-19. Drug colchicine (COL) presents recognized anti-inflammatory action, while the nanotechnology purpose therapies with low doses, efficacy, and decrease the drug's side-effects. This study aims to evaluate the effects of COL and colchicine nanocapsules (NCCOL) on survival, LC50, activity locomotor, and oxidative stress parameters, elucidating the toxicity profile in acute and chronic exposure in Drosophila melanogaster. Three-day-old flies were investigated into groups: Control, 0.001, 0.0025, 0.005, and 0.010 mg/mL of COL or NCCOL. The survival rate, open field test, LC50, oxidative stress markers (reactive species (RS) production, thiobarbituric acid reactive substances), antioxidant enzyme activity (catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase), protein thiols, nonprotein thiols, acetylcholinesterase activity, and cell viability were measured. As a result, acute exposure to the COL decreases the number of crosses in the open field and increases CAT activity. NCCOL reduced RS levels, increased lipoperoxidation and SOD activity. Chronic exposure to the COL and NCCOL in high concentrations implied high mortality and enzymatic inhibition of the CAT and AChE, and only the COL caused locomotor damage in the open field test. Thus, NCCOL again reduced the formation of RS while COL increased. In this comparative study, NCCOL was less toxic to the antioxidant system than COL and showed notable involvement of oxidative stress as one of their toxicity mechanisms. Future studies are needed to elucidate all aspects of nanosafety related to the NCCOL.

Effects of growth hormone/estrogen/androgen on COVID-19-type proinflammatory responses in normal human lung epithelial BEAS-2B cells.

BACKGROUND: COVID-19 is a disease caused by SARS-CoV-2, which can cause mild to serious infections in humans. We aimed to explore the effect of growth hormone (GH)/estrogen/androgen in normal human lung epithelial BEAS-2B cells on COVID-19-type proinflammatory responses. METHODS: A BEAS-2B COVID-19-like proinflammatory cell model was constructed. After that, the cells were treated with GH, 17ß-estradiol (E2), and testosterone (Tes) for 24 h. CCK-8 assays were utilized to evaluate cell viability. The mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 were measured by qRT‒PCR and Western blotting, respectively. ELISAs were performed to determine IL-6, MCP-1, MDA and SOD expression. Flow cytometry was used to measure ROS levels. Finally, MAPK/NF-κB pathway-related factor expression was evaluated. RESULTS: The COVID-19-type proinflammatory model was successfully constructed, and 1000 ng/mL RBD treatment for 24 h was selected as the condition for the model group for subsequent experiments. After RBD treatment, cell viability decreased, the mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 increased, IL-6, MCP-1, MDA and ROS levels increased, and MDA levels decreased. The mRNA levels of MAPK14 and RELA increased, but the protein levels did not change significantly. In addition, phospho-MAPK14 and phospho-RELA protein levels were also increased. Among the tested molecules, E2 had the most pronounced effect, followed by GH, while Tes showed the opposite effect. CONCLUSION: GH/E2 alleviated inflammation in a COVID-19-type proinflammatory model, but Tes showed the opposite effect.

The role of artificial cells in the fight against COVID-19: deliver vaccine, hemoperfusion removes toxic cytokines, nanobiotherapeutics lower free radicals and pCO2 and replenish blood supply.

This review concentrates on how artificial cells can contribute to helping patients with COVID-19. Artificial cells have led to mRNA vaccines with more improvements to come. Excessive cytokines in severe COVID-19 can damage organs leading to death. Artificial cell-based collodion macroporous activated charcoal adsorbent can effectively remove middle molecular weight range molecules in patients. A novel hemoperfusion device based on collodion membrane macroporous synthetic resin effectively removes cytokines and recovery in COVID-19 patients. This has been approved as an emergency treatment for COVID-19 in China, Europe, and Canada. A recent nanobiotherapeutic containing haemoglobin and up to six times the concentration of red blood cell enzymes: catalase, superoxide dismutase and carbonic anhydrase. In an animal study, this can effectively lower the damaging increase in free radicals and the removal of increased tissue pCO2. This can also help as blood substitute for the severe and critical problem of COVID-19 pandemic donor blood supply crisis.KEY MESSAGESCOVID-19 and its variants have resulted in major pandemics, severe sicknesses, and deaths around the world. COVID-19 and its variants has only started less than 3 years ago, and it is even more recently that we know more about its mechanisms, requirements, prevention, and treatment. This being the case, this is the first review on the present status and future perspectives of the use of the principle of artificial cells for COVID-19 related to vaccines, treatment, and critical donor blood supply shortage.

Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of inflammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the effects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. METHODS: Adult male rats were divided into five groups: the CN (healthy rats, n = 6), OA (oleic acid administration, n = 6), OA + TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n = 6), OA + TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n = 6), and OA + DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n = 6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. RESULTS: Expressions of TNF-α, IL-1ß, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P < 0.05). The MDA level in lung tissues was statistically lower in the OA + TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P < 0.05). Histopathological findings such as thickening of the alveoli, hyperemia, and peribronchial cell infiltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA + TCZ-2, and OA + TCZ-4 groups. CONCLUSIONS: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were effective in preventing cytokine storms by downregulating the expression of proinflammatory cytokines including TNF-α, IL-1ß, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective effects against cell damage.

Two-Dose Vaccination Significantly Prolongs the Duration from Symptom Onset to Death: A Retrospective Study Based on 173,894 SARS-CoV-2 Cases in Khyber Pakhtunkhwa, Pakistan.

This research was carried out to quantify the duration from symptom onset to recovery/death (SOR/SOD) during the first four waves and the Alpha/Delta period of the epidemic in Khyber Pakhtunkhwa, Pakistan, and identify the associated factors. A total of 173,894 COVID-19 cases were admitted between 16 March 2020 and 30 November 2021, including 458 intensive care unit (ICU) cases. The results showed that the case fatality rate (CFR) increased with age, and females had a higher CFR. The median SOR of ICU cases was longer than that of non-ICU cases (27.6 vs. 17.0 days), while the median SOD was much shorter (6.9 vs. 8.4 days). The SOR and SOD in the Delta period were slightly shortened than the Alpha period. Age, cardiovascular diseases, chronic lung disease, diabetes, fever, breathing issues, and ICU admission were risk factors that were significantly associated with SOD (p < 0.001). A control measure, in-home quarantine, was found to be significantly associated with longer SOD (odds ratio = 9.49, p < 0.001). Infected vaccinated individuals had longer SOD than unvaccinated individuals, especially for cases that had received two vaccine doses (p < 0.001). Finally, an advice on getting full-dose vaccination is given specifically to individuals aged 20-59 years.

Acute vaping in a golden Syrian hamster causes inflammatory response transcriptomic changes.

E-cigarette vaping is a major aspect of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of subacute and chronic e-cigarette vaping exposure have shown many proinflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting respiratory viruses, including SARS-CoV-2, without genetic alteration of the animal or virus. Using a 2-day, whole body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung, and nasal histopathology, and gene expression in the nasopharynx and lung through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal-Wallis tests. For tests that were statistically significant (P < 0.05), post hoc Tukey-Kramer and Dunn's tests, respectively, were performed to make pairwise comparisons between groups. In nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in gene expression associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis [transforming growth factor-ß (TGF-ß)], nicotine-independent increase oxidative stress response (SOD-2), and a nicotine-independent decrease in vasculogenesis/angiogenesis (VEGF-A). In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway [angiotensin-converting enzyme (ACE), ACE2], coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1ß, TNF-α, and CXCL-10), fibrosis (TGF-ß and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified. To our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cigarette vaping. In addition, this is the first report that e-cigarette vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation of mRNAs in the respiratory tract from pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, neutrophil extracellular trap release (NETosis), vasculogenesis, and angiogenesis.

Efficacy of Liriope platyphylla extract on improving respiratory function: A CONSORT-randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: The respiratory system is the first line of defense against outside pollutants. Recently, respiratory health has been receiving increasing attention due to the increase in fine dust, which reduces respiratory function and increases incidence of chronic obstructive pulmonary disease, and in coronavirus pandemic, which can cause severe acute respiratory syndrome. METHODS: This clinical pilot trial was designed to secure evidence for a main clinical trial and to confirm the efficacy and safety of Liriope platyphylla (LP) extract for improving respiratory function. We conducted a double-blind randomized placebo-controlled trial with 22 participants from June 30, 2021, to August 25, 2021. The primary outcome was Breathlessness, Cough, and Sputum Scale score. Secondary outcomes included forced vital capacity, forced expiratory volume at 1 second (FEV1), forced expiratory volume at 1 s/forced vital capacity ratio, cough assessment test score, chronic obstructive pulmonary disease assessment test score, peripheral blood mononuclear cell counts (white blood cells, eosinophils, T cells, and B cells), high-sensitivity C-reactive protein level, erythrocyte sedimentation rate, cytokine (interleukin-1ß, interleukin-4, tumor necrosis factor-α, interleukin-6, interleukin-8, interferon-γ, and immunoglobulin E) levels, antioxidant (glutathione peroxidase and superoxide dismutase) levels, and nitric oxide level. RESULTS: A total of 22 participants were randomly assigned to 2 groups: the LP group (n = 11), who took 1000 mg of LP extract per day, and the placebo group, who took 1000 mg of dextrin per day. Participants took 1 capsule twice a day for 4 weeks. For the Breathlessness, Cough, and Sputum Scale, the interaction between group and visit was statistically significant in a blend of analyses of variance. interleukin-8, tumor necrosis factor-α, and interferon-γ levels decreased more in the LP group than in the placebo group. The sample size required for large-scale clinical trials in the future was 50. There were no side effects. CONCLUSION: LP extract can enhance respiratory function. The detailed data we obtained support conducting the future main large-scale clinical trial.

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.

Cucumis melo var. momordica as a Potent Antidiabetic, Antioxidant and Possible Anticovid Alternative: Investigation through Experimental and Computational Methods.

Diabetes mellitus is a typical life threatening of disease, which generate due to the dysfunction of ß cells of pancreas. In 2014, WHO stated that 422 million people were infected with DM. The current pattern of management of diabetes included synthetic or plant based oral hypoglycemic drugs and insulin but drug resentence is become a very big issues in antidiabetic therapy. Thus, it's very earnest to discover now medication for this disease. Now the days, it is well acknowledged that diabetic patients are more prone towards covid and related complications. Thus, medical practitioners reformed the methodology of prescribing medication for covid infected antidiabetic therapy and encouraging the medication contains dual pharmacological properties. It is also well know that polyphenols specifically hold a significant role in oxidative stress and reduced the severity of many inflammatory diseases. Cucumis melo has rich history as ethano-pharmacological use in Indian subcontinent. The fruit and seed are well-known for the treatment of various diseases due to the presence of phenolics. Therefore, in this study, the combined mixture of flower and seeds were used for the extraction of polyphenolic rich extract and tested for antidiabetic activity through the antioxidant and in vivo experiments. The antioxidant potential measurement exhibited that the selected plant extract has the significant competence to down-regulate oxidative stress (DPPH scavenging IC50 at 60.7±1.05 µg/mL, ABTS IC50 at 62.15±0.50 µg/mL). Furthermore, the major polyphenolic phyto-compounds derived from the Cucumis melo were used for in silico anticovid activity, docking, and complementarity studies. The anticovid activity prognosis reflected that selected phyto-compounds amentoflavone and vanillic acid have optimal possibility to interact with 3C-like protease and through this moderate anticovid activity can be exhibit. The docking experiments established that the selected compounds have propensity to interact with protein tyrosine phosphatase 1B, 11ß-Hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, and catalase ß-glucuronidase receptor. In vivo experiments showed that 500 mg/kg, Cucumis melo extract ominously amplified body weight, plasma insulin, high-density lipoprotein levels, and biochemical markers. Furthermore, extract significantly downregulate the blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein.

Short-term exposure of the mayfly larvae (Cloeon dipterum, Ephemeroptera: Baetidae) to SARS-CoV-2-derived peptides and other emerging pollutants: A new threat for the aquatic environments.

The input of SARS-CoV-2 or its fragments into freshwater ecosystems (via domestic or hospital sewage) has raised concerns about its possible impacts on aquatic organisms. Thus, using mayfly larvae [Cloeon dipterum (L.), Ephemeroptera: Baetidae] as a model system, we aimed to evaluate the possible effects of the combined short exposure of SARS-CoV-2-derived peptides (named PSPD-2001, PSPD-2002, and PSPD-2003 - at 266.2 ng/L) with multiple emerging pollutants at ambient concentrations. After six days of exposure, we observed higher mortality of larvae exposed to SARS-CoV-2-derived peptides (alone or in combination with the pollutant mix) and a lower-body condition index than those unexposed larvae. In the "PSPD" and "Mix+PSPD" groups, the activity of superoxide dismutase, catalase, DPPH radical scavenging activity, and the total thiol levels were also lower than in the "control" group. In addition, we evidenced the induction of nitrosative stress (inferred by increased nitrite production) and reduced acetylcholinesterase activity by SARS-CoV-2-derived peptides. On the other hand, malondialdehyde levels in larvae exposed to treatments were significantly lower than in unexposed larvae. The values of the integrated biomarker response index and the principal component analysis (PCA) results confirmed the similarity between the responses of animals exposed to SARS-CoV-2-derived peptides (alone and in combination with the pollutant mix). Although viral peptides did not intensify the effects of the pollutant mix, our study sheds light on the potential ecotoxicological risk associated with the spread of the new coronavirus in aquatic environments. Therefore, we recommend exploring this topic in other organisms and experimental contexts.

Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action.

BACKGROUND: Melatonin is an indole hormone secreted primarily by the pineal gland that showing anti-oxidant, anti-inflammatory and anti-apoptotic capacity. It can play an important role in the pathophysiological mechanisms of various diseases. In this regard, different studies have shown that there is a relationship between Melatonin and Multiple Sclerosis (MS). MS is a chronic immune-mediated disease of the Central Nervous System. AIM: The objective of this review was to evaluate the mechanisms of action of melatonin on oxidative stress, inflammation and intestinal dysbiosis caused by MS, as well as its interaction with different hormones and factors that can influence the pathophysiology of the disease. RESULTS: Melatonin causes a significant increase in the levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione and can counteract and inhibit the effects of the NLRP3 inflammasome, which would also be beneficial during SARS-CoV-2 infection. In addition, melatonin increases antimicrobial peptides, especially Reg3ß, which could be useful in controlling the microbiota. CONCLUSION: Melatonin could exert a beneficial effect in people suffering from MS, running as a promising candidate for the treatment of this disease. However, more research in human is needed to help understand the possible interaction between melatonin and certain sex hormones, such as estrogens, to know the potential therapeutic efficacy in both men and women.

Superoxide Dismutase Activity in Male and Female Patients of Different Age with Moderate COVID-19.

The study involved 271 patients (132 men and 139 women) with moderate COVID-19. Superoxide dismutase (SOD) activity in erythrocytes was measured spectrophotometrically. In total group of patients (divided into age groups of 18-35, 36-45, 46-60, and 61-90 years), higher SOD activity was found in the 18-35 age group in comparison with the groups 46-60 years (p<0.01) and 61-90 years (p<0.05). Then, the groups were additionally divided by sex. In men, no differences in enzyme activity were found between the age groups. In women of early reproductive age, SOD activity was higher than in groups 36-45, 46-60, and 61-90 years. The sex differences consisted in higher SOD activity in women aged 18-35 years in comparison with men of this age. These data should be taken into account when choosing the tactics of therapy for patients with moderate COVID-19 course.

SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort.

Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters.Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients' laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009).Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antiox-idant therapy.

Total antioxidant capacity as a marker of severity of COVID-19 infection: Possible prognostic and therapeutic clinical application.

The pathogenesis of SARS-CoV-2 infection, causative pathogen of the known COVID-19 pandemic is not well clarified. In this regard oxidative stress is one of the topics that need to be investigated. Therefore, the present research was performed to explore the relationship between the oxidant/antioxidant system and COVID-19 exacerbation. Sera were collected from 120 patients with COVID-19 infection and 60 healthy volunteers as the control group. The patient group consisted of 60 cases with mild disease and 60 severely ill patients. Serum levels of total antioxidant capacity (TAC) and nitric oxide (NO) as well as serum activities of the two main antioxidant defense enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured. TAC levels were considerably lower in patients compared with healthy individuals (p < 0.05) and also between patients with mild and severe diseases (p < 0.05). A rather decreasing trend was also found in NO concentration as well as SOD and CAT activity, though, the observed differences were not statistically significant (p > 0.05). These findings suggest that COVID-19 patients may be susceptible to depleted total antioxidant capacity. Moreover, showing such variations in blood samples of infected individuals could be considered as a predictive marker of COVID-19 severity.

Changes in oxidative markers in COVID-19 patients.

AIM AND BACKGROUND: Covid-19 has been as an important human infectious disease that has affected several countries. Cytokine storm has major role is Covid-19 pathogenesis. The association between inflammation and oxidative stress is well stablished. In this article, we aim to assess oxidative stress markers in Covid-19 patients compare to the healthy subjects. METHOD: A total of 48 persons (24 with Covid-19 and 24 controls) were evaluated in this research. Serum oxidative stress markers including Malondialdehyde (MDA), total oxidant status (TOS), activity of catalase (CAT) and super oxide dismutase (SOD) were measured alongside routine laboratory tests. RESULTS: Patients group were divided into ICU and Non-ICU groups. ESR, CRP and serum level of ferritin were significantly higher in case group. Serum level of albumin was significantly lower in Covid-19 patients. Serum MDA and TOS was significantly increased in Covid-19 patients. Also, Covid-19 patients had higher serum activity of CAT and GPX. CONCLUSION: Oxidative stress markers are significantly elevated in Covid-19 patients. This may have significant role in mechanism of disease development. In the fight against Covid-19, as a global struggle, all possible treatments demand more attention. So, Covid-19 patients may benefit from strategies for reducing or preventing oxidative stress.

Comparative investigation of toxicity induced by UV-A and UV-C radiation using Allium test.

Organisms are increasingly exposed to ultraviolet (UV) rays of sunlight, due to the thinning of the ozone layer and its widespread use in sterilization processes, especially against the SARS-CoV-2 virus. The present study was conducted with the purpose of evaluating the damages of UV-A and UV-C radiations in Allium cepa L. roots. The effects of two different types of UV on some physiological, biochemical, cytogenotoxic, and anatomical parameters were investigated in a multifaceted study. Three groups were formed from Allium bulbs, one of which was the control group. One of the other groups was exposed to 254 nm (UV-C) and the other to 365 nm (UV-A) UV. Growth retardation effect of UV was investigated with respect to germination percentage, total weight gain, and root elongation, while cytogenotoxicity arisen from UV exposure was analyzed using mitotic index (MI) and chromosomal aberration (CA) and micronucleus (MN) frequency. Oxidative stress due to UV application was investigated based on the accumulation of malondialdehyde (MDA) and the total activities of superoxide dismutase (SOD) and catalase (CAT) enzymes. Also, anatomical changes induced by UV-A and UV-C were analyzed in root meristematic cells. UV treatments caused significant reductions in growth-related parameters. Both UV treatments caused a significant increase in MDA levels and induction of SOD and CAT enzymes in root meristematic cells. A decrease in MI and an increase in the frequency of MN and CAs were observed in root tip cells, indicating the cytogenotoxic effect of UV application. Anatomical damages such as epidermis cell damage, cortex cell damage, necrotic zones, giant cell nucleus, and indistinct transmission tissue occurred in cells exposed to UV. All of the physiological, biochemical, cytogenetic, and anatomical damages observed in this study were more severe in cells treated with UV-C compared to UV-A. This study suggested that UV exposure triggered growth inhibition, cytogenotoxicity, oxidative stress, and meristematic cell damages in A. cepa roots depending on the wavelength.

Essential metals, vitamins and antioxidant enzyme activities in COVID-19 patients and their potential associations with the disease severity.

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.