Angiotensin converting enzyme 2 gene expression and markers of oxidative stress are correlated with disease severity in patients with COVID-19.

BACKGROUND: Oxidative stress is thought to play a significant role in the pathogenesis and severity of COVID-19. Additionally, angiotensin converting enzyme 2 (ACE2) expression may predict the severity and clinical course of COVID-19. Accordingly, the aim of the present study was to evaluate the association of oxidative stress and ACE2 expression with the clinical severity in patients with COVID-19. METHODS AND RESULTS: The present study comprised 40 patients with COVID-19 and 40 matched healthy controls, recruited between September 2021 and March 2022. ACE 2 expression levels were measured using Hera plus SYBR Green qPCR kits with GAPDH used as an internal control. Serum melatonin (MLT) levels, serum malondialdehyde (MDA) levels, and total antioxidant capacity (TAC) were estimated using ELISA. The correlations between the levels of the studied markers and clinical indicators of disease severity were evaluated. Significantly, lower expression of ACE2 was observed in COVID-19 patients compared to controls. Patients with COVID-19 had lower serum levels of TAC and MLT but higher serum levels of MDA compared to normal controls. Serum MDA levels were correlated with diastolic blood pressure (DBP), Glasgow coma scale (GCS) scores, and serum potassium levels. Serum MLT levels were positively correlated with DBP, mean arterial pressure (MAP), respiratory rate, and serum potassium levels. TAC was correlated with GCS, mean platelet volume, and serum creatinine levels. Serum MLT levels were significantly lower in patients treated with remdesivir and inotropes. Receiver operating characteristic curve analysis demonstrates that all markers had utility in discriminating COVID-19 patients from healthy controls. CONCLUSIONS: Increased oxidative stress and increased ACE2 expression were correlated with disease severity and poor outcomes in hospitalized patients with COVID-19 in the present study. Melatonin supplementation may provide a utility as an adjuvant therapy in decreasing disease severity and death in COVID-19 patients.

Epigallocatechin-3-gallate Enhances Cognitive and Memory Performance and Protects Against Brain Injury in Methionine-induced Hyperhomocysteinemia Through Interdependent Molecular Pathways.

Brain injury and cognitive impairment are major health issues associated with neurodegenerative diseases in young and aged persons worldwide. Epigallocatechin-3-gallate (EGCG) was studied for its ability to protect against methionine (Met)-induced brain damage and cognitive dysfunction. Male mice were given Met-supplemented in drinking water to produce hyperhomocysteinemia (HHcy)-induced animals. EGCG was administered daily concurrently with Met by gavage. EGCG attenuated the rise in homocysteine levels in the plasma and the formation of amyloid-ß and tau protein in the brain. Cognitive and memory impairment in HHcy-induced mice were significantly improved by EGCG administration. These results were associated with improvement in glutamate and gamma-aminobutyric acid levels in the brain. EGCG maintained the levels of glutathione and the activity of antioxidant enzymes in the brain. As a result of the reduction of oxidative stress, EGCG protected against DNA damage in Met-treated mice. Moreover, maintaining the redox balance significantly ameliorated neuroinflammation evidenced by the normalization of IL-1ß, IL-6, tumor necrosis factor α, C-reactive protein, and IL-13 in the same animals. The decreases in both oxidative stress and inflammatory cytokines were significantly associated with upregulation of the antiapoptotic Bcl-2 protein and downregulation of the proapoptotic protein Bax, caspases 3 and 9, and p53 compared with Met-treated animals, indicating a diminution of neuronal apoptosis. These effects reflect and explain the improvement in histopathological alterations in the hippocampus of Met-treated mice. In conclusion, the beneficial effects of EGCG may be due to interconnecting pathways, including modulation of redox balance, amelioration of inflammation, and regulation of antiapoptotic proteins.

Polyphenols are potential nutritional adjuvants for targeting COVID-19.

The newly emerging severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) is a dangerous pathogen that causes global health problems. It causes a disease called coronavirus disease 2019 (COVID-19) with high morbidity and mortality rates. In SARS-Cov-2-infected patients, elevated oxidative stress and upsurge of inflammatory cytokines are the main pathophysiological events that contribute to the severity and progression of symptoms and death. The polyphenols are natural compounds abundant in fruits and vegetables that are characterized by their high antioxidant and anti-inflammatory effects. Polyphenols have potential as an intervention for preventing respiratory virus infection. The beneficial effects of polyphenols on COVID-19 might be due to multiple mechanisms. Polyphenols can strengthen the body's anti-inflammatory and antioxidant defenses against viral infection. Targeting virus proteins and/or blocking cellular receptors are other plausible antiviral approaches to prevent the entry of the virus and its replication in the host cells. The results on the antiviral effects of various polyphenols, especially on SARS-CoV-2, are promising. The aim of this review is to clarify the role of polyphenols in strengthening antioxidant defenses and upregulating the immune systems of COVID-19 patients and to prevent replication and spreading of the virus.

Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19.

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages. The Covid-19 takes a more severe course in individuals with chronic metabolic diseases such as obesity, diabetes mellitus, and hypertension. This category of persons exhibits weak immune activity and decreased levels of endogenous antioxidants. Melatonin is a multifunctional signaling hormone synthesized and secreted primarily by the pineal gland. It is a potent antioxidant with immunomodulatory action and has remarkable anti-inflammatory effects under a variety of circumstances. Regarding Covid-19 and metabolic syndrome, adequate information about the relationship between these two comorbidities is required for better management of these patients. Since Covid-19 infection and complications involve severe inflammation and oxidative stress in people with obesity and diabetes, we anticipated the inclusion of melatonin, as powerful antioxidant, within proposed treatment protocols. In this context, melatonin is a potential and promising agent to help overcome Covid-19 infection and boost the immune system in healthy persons and obese and diabetic patients. This review summarizes some evidence from recently published reports on the utility of melatonin as a potential adjuvant in Covid-19-infected individuals with diabetes and obesity.

Ameliorative effects of melatonin against solid Ehrlich carcinoma progression in female mice.

The current work estimated the antitumour efficacy of melatonin (MLT) on the growth of Ehrlich ascites carcinoma cells inoculated intramuscularly into the hind limbs of female BALB/c mice and to compare its effects with those of adriamycin (ADR). After solid tumours developed, the animals were divided into the three following groups: the tumour-bearing control, MLT-treated (20 mg/kg body weight) and ADR-treated (10 mg/kg body weight) groups. The results showed a significant reduction in the tumour masses of the treated animals in comparison with those of the control group. There were a significant decrease in the malondialdehyde level and a significant elevation of the glutathione concentration and the superoxide dismutase and catalase activities in the MLT and ADR groups. The current study indicated the increased expression levels of P53, caspase-3 and caspase-9 and the decreased expression levels of the rRNA and Bcl2. The MLT and ADR treatments resulted in histological changes, such as a marked degenerative area, the necrosis of neoplastic cells, the appearance of different forms of apoptotic cells and giant cells with condensed chromatin, and a deeply eosinophilic cytoplasm. The MLT and ADR treatments also significantly decreased the Ki-67 protein and vascular endothelial growth factor (VEGF) expression levels in the tumour masses. In conclusion, similar to ADR-treated tumour-bearing mice, MLT suppressed the growth and proliferation of tumour by inducing apoptosis and by inhibiting tumour vascularization. The current data recommend MLT as a safe natural chemotherapeutic adjuvant to overcome cancer progression after a clinical trial validates these results.

Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats.

The potential protective effect of epigallocatechin-3-gallate (EGCG) on type 2 diabetes-induced heart injury was investigated. A rat model of diabetes was achieved by injection of nicotinamide (100mg/kg, i.p), 20min before the administration of streptozotocin (55mg/kg, i.p.). After confirmation of diabetes, EGCG (2mg/kg, p.o.) was administrated on alternate days for one month. Treatment of diabetic rats with EGCG showed a remarkable reduction in glucose, glycosylated hemoglobin, HOMA-IR and lipid profile levels with an elevation in insulin levels, indicating its antihyperglycemic and antidyslipidemic actions. EGCG treatment also suppressed the increase in the levels of superoxide, 4-hydroxynonenal and protein carbonyl, whereas it increased the content of glutathione and the activities of superoxide dismutase and catalase in heart of diabetic rats, indicating its antioxidant capacity. In addition, EGCG improved heart function of diabetic rats as evidenced by a remarkable reduction in troponin T level and creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase activities in the serum. Oral administration of EGCG for one month after diabetes induction significantly protected the increase in serum levels of pro-inflammatory cytokines (IL-1 ß, IL-6 and TNF-α) and adhesion molecules (ICAM-1 and VCAM-1), suggesting its anti-inflammatory potential. Furthermore, EGCG hampered the mitochondrial apoptotic pathway through increasing Bcl-2 level and decreasing p53, Bax, cytochrome c and caspase-3 and 9 levels in hearts of diabetic rats, indicating its anti-apoptotic action. Diabetic rats treated with EGCG also exhibited decreased level of DNA damage in the myocardium. The histological examinations indicated the cardioprotective effect of EGCG against harmful impact of diabetes. Therefore, these findings suggest that EGCG has a protective effect on the heart affected by type 2 diabetes and recommend it as a complementary supplement for diabetic patients.

Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity.

Epidemiological reports have indicated a correlation between the increasing bisphenol A (BPA) levels in the environment and the incidence of male infertility. In this study, the protective effects of melatonin on BPA-induced oxidative stress and apoptosis were investigated in the rat testes and epididymal sperm. Melatonin (10 mg/kg body weight (bw)) was injected concurrently with BPA (50 mg/kg bw) for 3 and 6 weeks. The administration of BPA significantly increased oxidative stress in the testes and epididymal sperm. This was associated with a decrease in the serum testosterone level as well as sperm quality, chromatin condensation/de-condensation level, and the percentage of haploid germ cells in the semen. BPA administration caused a significant increase in apoptosis accompanied by a decrease in the expression of the antiapoptotic proteins Bcl-2 in the testes and epididymal sperm. The concurrent administration of melatonin decreased oxidative stress by modulating the levels of glutathione, superoxide dismutase, and catalase as well as the malondialdehyde and hydrogen peroxide concentrations in the testes and sperm. Melatonin sustained Bcl-2 expression and controlled apoptosis. Furthermore, melatonin maintained the testosterone levels, ameliorated histopathological changes, increased the percentages of seminal haploid germ cells, and protected sperm chromatin condensation process, indicating appropriate spermatogenesis with production of functional sperm. In conclusion, melatonin protected against BPA-induced apoptosis by controlling Bcl-2 expression and ameliorating oxidative stress in the testes and sperm. Thus, melatonin is a promising pharmacological agent for preventing the potential reproductive toxicity of BPA following occupational or environmental exposures.