Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19

Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have recovered, while seven passed away. There were no differences between them in respect to clinical or laboratory parameters monitored. However, protein adducts of the lipid peroxidation product 4-hydroxynonenal (HNE) were higher in the plasma of the deceased patients, while total antioxidant capacity was below the detection limit for the majority of sera samples in both groups. Moreover, levels of the HNE-protein adducts were constant in the plasma of the deceased patients, while in survivors, they have shown prominent and dynamic variations, suggesting that survivors had active oxidative stress response mechanisms reacting to COVID-19 aggression, which were not efficient in patients who died. Immunohistochemistry revealed the abundant presence of HNE-protein adducts in the lungs of deceased patients indicating that HNE is associated with the lethal outcome. It seems that HNE was spreading from the blood vessels more than being a consequence of pneumonia. Due to the limitations of the relatively small number of patients involved in this study, further research on HNE and antioxidants is needed. This might allow a better understanding of COVID-19 and options for utilizing antioxidants by personalized, integrative biomedicine approach to prevent the onset of HNE-mediated vitious circle of lipid peroxidation in patients with aggressive inflammatory diseases.

Dual Mechanisms of Cardiac Action Potential Prolongation by 4-Oxo-Nonenal Increasing the Risk of Arrhythmia; Late Na+ Current Induction and hERG K+ Channel Inhibition

4-Oxo-nonenal (4-ONE) is an endogenous lipid peroxidation product that is more reactive than 4-hydroxy-nonenal (4-HNE). We previously reported the arrhythmic potential of 4-HNE by suppression of cardiac human Ether-a-go-go Related Gene (hERG) K+ channels with prolonged action potential duration (APD) in cardiomyocytes. Here, we illustrate the higher arrhythmic risk of 4-ONE by modulating the cardiac hNaV1.5 channel currents (INaV). Although the peak amplitude of INaV was not significantly changed by 4-ONE up to 10 μM, the rate of INaV inactivation was slowed, and the late Na+ current (INaL) became larger by 10 μM 4-ONE. The chemical modification of specific residues in hNaV1.5 by 4-ONE was identified using MS-fingerprinting analysis. In addition to the changes in INaV, 4-ONE decreased the delayed rectifier K+ channel currents including the hERG current. The L-type Ca2+ channel current was decreased, whereas its inactivation was slowed by 4-ONE. The APD prolongation by 10 μM of 4-ONE was more prominent than that by 100 μM of 4-HNE. In the computational in silico cardiomyocyte simulation analysis, the changes of INaL by 4-ONE significantly exacerbated the risk of arrhythmia exhibited by the TdP marker, qNet. Our study suggests an arrhythmogenic effect of 4-ONE on cardiac ion channels, especially hNaV1.5.

Protective Effect of Resveratrol on Hepatocyte Apoptosis in Alcoholic Liver

Resveratrol is a phytoalexin produced by several plants. To investigate its mechanism on prevention of alcoholic liver injury, 72 male rats with alcoholic liver disease were randomly divided into 6 groups (blank, model, positive drug, high, medium and low dose of resveratrol groups). After 30 days of continuous feeding, the levels of various indexes were detected; TUNEL assay was used to detect the apoptosis of liver cells; the expression of CYP2E1, SIRT-1, NF-κB and TNF-α was detected by western blot. In the results, the activities of Alanine transaminase (ALT), Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), low-density lipoprotein cholesterol (LDL-C), total bilirubin (TBIL) and y-glutamyl transferase (GGT) in serum of resveratrol groups were significantly lower than those of model control group, the activity of glutathione (GSH) and superoxide dismutase (SOD) in high and medium dose resveratrol group was significantly increased. The contents of Lipid peroxidation product malondialdehyde (MDA) and Reactive Oxygen Species (ROS) in the groups with high, medium and low doses of resveratrol were significantly reduced. Resveratrol could significantly reduce the protein expression of CYP2E1, NF-κB and TNF-α in rat liver tissue; the protein expression of SIRT-1 was significantly up-regulated. In conclusion, resveratrol has a remarkable antioxidant effect.

Piper Nigrum Protects Against Fe (II) Mediated Lipid Peroxidation in Phopholipids Liposomes: Analytical and Biochemical Analysis

Phospholipids liposomes were employed to access the extent of Iron [Fe(II)] induced lipid peroxidation. Our data indicate that Fe(II) caused a significant increase in malondialdehyde (MDA) formation, a lipid peroxidation product. Ethanolic extract of Piper Nigrum (PN) significantly inhibited lipid peroxidation at the highest tested concentrations. The plant with three different extracts (aqueous, ethanolic, and ethyl acetate)was tested for its nutritional value, and a higher amount of carbohydrates (42.66%), fibers (20.96 %), and proteins (14.38 %) were recorded. The mineral content evaluated by atomic absorption spectrophotometry (AAS) showed Ca (30.400 mg/L), Mg (10.475 mg/L), and Mn (2.391 mg/L) in higher concentrations. Quantitative gas chromatographic analysis coupled with a mass spectrometer (GCMS) was used to explore the characteristic biochemical compounds, which confirmed the presence of twenty-four (24) active constituents. D-Limonene (18.59%) was present in higher concentrations, followed by beta-pinene (17.98%), alpha-pinene (12.85%), and caryophyllene (9.91%). Plant extracts and essential oil were further tested against six (6) gram-negative, three (3) gram-positive, and a fungal strain by disc diffusion method. The presence of active compounds in essential oil and crude extracts may be responsible for observed pharmacological efficacies of PN and can be considered as a nutraceutical for the treatment of oxidative stress-related and pathogenic diseases.

Psoriasis, An inflammatory condition associated with oxidative stress

Background: Psoriasis is a chronic inflammatory skin disease characterized by pathological skin lesions due to various exogenous and endogenous factors. Oxidative stress can be one of the causes for the occurrence of psoriasis as well as significant contributor to its progression. Skin exposure to a number of irritants or proinflammatory agents including UVA and UVB generates ROS through the oxidative burst in infiltrating leukocytes at the site of inflammation which damages the skin cells. Measurement of the oxidative stress marker like lipid peroxidation product Malondialdehyde (MDA) and Nitric Oxide end products (NO2+NO3) along with the inflammatory marker hs-CRP in Psoriasis patients can uncover their role in disease causation, progression and development of various co-morbidities and timely prevention can significantly improve the quality of life of the psoriasis patients. Aims and Objectives: To measure the oxidative stress marker like lipid peroxidation product Malondialdehyde (MDA) and Nitric Oxide end products (NO2+NO3) along with the inflammatory marker hs-CRP in Psoriasis patients to uncover their role in disease causation, progression and development of various co-morbidities and timely prevention to significantly improve the quality of life of the psoriasis patients. Materials and Methods: Fifty patients of psoriasis mainly plaque type of either sex, in the age group of 35 ± 15.5 (range: 7-79) years were taken following inclusion and exclusion criteria. To evaluate the oxidative stress lipid peroxidation product malondialdehyde (MDA) and Nitric Oxide end products (NO2 + NO3) were measured. hs-CRP was measured as an inflammatory marker and their correlation with the disease severity and duration was evaluated. Results: A significant increase in malondialdehyde (MDA), Nitric Oxide end products (NOx) and hs-CRP levels (P<0.001) was noted in Psoriatic patients as compared to controls. There was a positive correlation between MDA, NOx and hs-CRP levels with the severity and duration of the disease. The correlation between hs-CRP and MDA and NOx also showed positive trend. Conclusion: Oxidative stress is one of the factors which can lead to the causation of Psoriasis and also significantly contribute to the disease progression and development of various co-morbidities. By measuring the oxidative stress marker and inflammatory marker in psoriasis patients early in the disease process we can employ preventive strategies for better management and improve the survival and quality of life.

White oak (Quercus fabri Hance) regenerated stump sprouts show few senescence symptoms during 40 years of growth in a natural forest

Background The relationship between physiological age of parental trees and lifespan of clonal offspring is unclear. White oak (Quercus fabri Hance) has a high sprouting capability after harvest, with the regenerated sprouts being typical clonal individuals. To determine whether regenerated sprouts undergo rapid senescence compared with the parent, the senescence levels of 5-, 10-, 20- and 40-year-old regenerated stump sprouts in a natural forest were evaluated. The antioxidative abilities and transcriptomes in these leaves and shoots were compared. Results Older regenerated sprouts still had robust antioxidative systems, with 40-year-old sprouts having lower peroxidation product levels but similar antioxidative enzyme activity levels compared with 5-year-old sprouts. Older leaves had greater transcriptional activities in pathways related to cell growth and division than younger leaves. However, older sprouts had some unhealthy characteristics, such as increased base excision repair levels and upregulated phagosome, proteasome and glycerophospholipid metabolism pathways in 40-year-old leaves, which indicates that DNA damage and tissue remodeling occurred more frequently than in younger leaves. Additionally, plant-pathogen interactions and MAPK signals pathways were upregulated in older shoots, which indicates that older shoots suffered from more pathogen-related biotic stress. Conclusions The 40-year-old sprouts still had the same vitality level as the 5-year-old sprouts, although the former had some unhealthy characteristics. We conclude that during their first 40 years of growth, regenerated stump sprouts do not begin to senesce, and that physiological age of parental trees does not significantly affect the lifespan of its clonal offspring.

White oak (Quercus fabri Hance) regenerated stump sprouts show few senescence symptoms during 40 years’ growth in a natural forest

Background: The relationship between the parental tree’s physiological age and the clonal offspring’s lifespan is unclear. White oak (Quercus fabri Hance) has a high sprouting capability after harvest, with the regenerated sprouts being typical clonal individuals. To determine whether regenerated sprouts undergo rapid senescence compared with the parent, the senescence levels of 5-, 10-, 20- and 40-year-old regenerated stump sprouts in a natural forest were evaluated. The antioxidative abilities and transcriptomes in these leaves and shoots were compared. Results: Older regenerated sprouts still had robust antioxidative systems, with 40-year-old sprouts having lower peroxidation product levels but similar antioxidative enzyme activity levels compared with 5-year-old sprouts. Older leaves had greater transcriptional activities in pathways related to cell growth and division than younger leaves. However, older sprouts had some unhealthy characteristics, such as increased base excision repair levels and upregulated phagosome, proteasome and glycerophospholipid metabolism pathways in 40-year-old leaves, which indicates that DNA damage and tissue remodeling occurred more frequently than in younger leaves. Additionally, plant–pathogen interactions and MAPK signals pathways were upregulated in older shoots, which indicates that older shoots suffered from more pathogen-related biotic stress. Conclusions: The 40-year-old sprouts still had the same vitality level as the 5-year-old sprouts, although the former had some unhealthy characteristics. We conclude that during their first 40 years of growth, regenerated stump sprouts do not begin to senesce, and that the parental tree’s physiological age does not significantly affect its clonal offspring’s lifespan.