Outcome of COVID-19: Diabetes and Obesity

Today the world is facing one of the biggest crisis, due to a new beta-corona virus emerged from Wuhan in China, on December 2019. WHO declared ‘acute respiratory syndrome COVID-19 (SARS Co-2)’as a pandemic on March 12, 2020. Corona viruses are enveloped positive single stranded RNA viruses, causing severe acute respiratory syndrome in the infected individuals. The risk of getting infected by covid-19 is similar in all the individuals across the nation. But the outcome of the infection varies from one individual to another, depending on the comorbidities present in them. The most vulnerable group of patients in respect to severity of outcome of the infection are the once with unbalanced heath conditions like age (>65 years), immune-compromised, hypertension, type 2 diabetes, increased insulin resistance, cardiovascular diseases, chronic kidney disease, chronic liver disease, vasculitis(vascular inflammation)and obesity. It is now a public knowledge that diabetes and obesity are a risk factor for any individual as these conditions can exacerbate the manifestations of COVID-19 infections thus increasing the severity of the condition, that may require hospitalization of the patient, later may even require intensive care unit or/and mechanical ventilation, with increased risk of mortality rates. In diabetic patients it is mainly due to failure in controlling the glucose levels and the risk of ketoacidosis. In patients with obesity lipid peroxidase creates reactive lipid aldehydes leading to poor prognosis.

The Role of Lipoxidation in the Pathogenesis of Diabetic Retinopathy

Lipids can undergo modification as a result of interaction with reactive oxygen species (ROS). For example, lipid peroxidation results in the production of a wide variety of highly reactive aldehyde species which can drive a range of disease-relevant responses in cells and tissues. Such lipid aldehydes react with nucleophilic groups on macromolecules including phospholipids, nucleic acids, and proteins which, in turn, leads to the formation of reversible or irreversible adducts known as advanced lipoxidation end products (ALEs). In the setting of diabetes, lipid peroxidation and ALE formation has been implicated in the pathogenesis of macro- and microvascular complications. As the most common diabetic complication, retinopathy is one of the leading causes of vision loss and blindness worldwide. Herein, we discuss diabetic retinopathy (DR) as a disease entity and review the current knowledge and experimental data supporting a role for lipid peroxidation and ALE formation in the onset and development of this condition. Potential therapeutic approaches to prevent lipid peroxidation and lipoxidation reactions in the diabetic retina are also considered, including the use of antioxidants, lipid aldehyde scavenging agents and pharmacological and gene therapy approaches for boosting endogenous aldehyde detoxification systems. It is concluded that further research in this area could lead to new strategies to halt the progression of DR before irreversible retinal damage and sight-threatening complications occur.

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.

Two Toxic Lipid Aldehydes, 4-hydroxy-2-hexenal (4-HHE) and 4-hydroxy-2-nonenal (4-HNE), Accumulate in Patients with Chronic Kidney Disease

Lipid aldehydes originating from the peroxidation of n-3 and n-6 polyunsaturated fatty acids are increased in hemodialysis (HD) patients, a process already known to promote oxidative stress. However, data are lacking for patients with chronic kidney disease (CKD) before the initiation of HD. We prospectively evaluated the changes of plasma concentrations of two major lipid aldehydes, 4-HHE and 4-HNE, according to the decrease of glomerular filtration rate (GFR) in 40 CKD and 13 non-CKD participants. GFR was measured by inulin or iohexol clearance. Thus, 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE) were quantitated in plasma by gas chromatography coupled with mass spectrometry and their covalent adducts on proteins were quantified by immunoblotting. On the one hand, 4-HHE plasma concentration increased from CKD stage I–II to CKD stage IV–V compared to non-CKD patients (4.5-fold higher in CKD IV–V, p < 0.005). On the other hand, 4-HNE concentration only increased in CKD stage IV–V patients (6.2-fold, p < 0.005). The amount of covalent adducts of 4-HHE on plasma protein was 9.5-fold higher in CKD patients than in controls (p < 0.005), while no difference was observed for 4-HNE protein adducts. Plasma concentrations of 4-HNE and 4-HHE are increased in CKD IV–V patients before the initiation of hemodialysis.

Impact of oxidative stress on male and female germ cells: implications for fertility

Male and female germ lines are vulnerable to oxidative stress. In spermatozoa, such stress triggers a lipid peroxidation cascade that culminates in the generation of electrophilic lipid aldehydes that bind to DNA and a raft of proteins involved in the delivery of functionally competent cells. One set of targets for these aldehydes are the proteins of the mitochondrial electron transport chain. When this interaction occurs, mitochondrial ROS generation is enhanced leading to the sustained generation of oxidative damage in a self-perpetuating cycle. Such damage affects all aspects of sperm function including motility, sperm-egg recognition, acrosomal exocytosis and sperm-oocyte fusion. Oxidative stress in the male germ line also attacks the integrity of sperm DNA with potential impacts on the developmental capacity of embryos and the health and wellbeing of the offspring. Potential pathways of reactive oxygen species (ROS) generation in male germ cells could involve enhanced lipoxygenase activity, activation of NADPH oxidase and/or electron leakage from mitochondria. Similarly, in the female germ line, both the induction of oocyte senescence following ovulation and the deterioration of oocyte quality with maternal age appear to involve the generation of oxidative damage. In this case, the mitochondria appear to be a particularly important source of ROS compromising the viability and fertilizability of the oocyte and interfering with the normal segregation of chromosomes during meiosis. In light of these considerations, antioxidants should have some role to play in the preservation of reproductive function in both men and women; however, we still await appropriate trials to test this hypothesis.

Free Radical Scavenging Activity of Carbonyl-Amine Adducts Formed in Soybean Oil Fortified with Phosphatidylethanolamine

Non-enzymatic browning reactions between lipid aldehydes and aminophospholipids might play an important role in the oxidative stability of cold-pressed vegetable oils. We, therefore, aimed to study the Maillard-type reaction between hexanal, a lipid oxidation product of linoleic acid, and phosphatidylethanolamine (PE (16:0/18:1)) at a ratio of 2:1 at conditions representative of the extraction of cold-pressed soybean oils (CPSBO) and determine the radical scavenging activity of the carbonyl-amine adducts with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The reaction product, 2-pentyl-3,5-dibutyl-dihydropyridine, could be identified by means of LC-ESI-QTOF-MS/MS. The formation of this nitrogen-containing heterocycle significantly increased with time and temperature (p < 0.05). The products formed during the carbonyl-amine reaction between PE (16:0/18:1) and hexanal at 60 °C showed a radical scavenging activity of approximately 20% (p < 0.05). The fraction, containing 2-pentyl-3,5-dibutyl-dihydropyridine, contributed to, but was not solely responsible for, the radical scavenging activity (p < 0.05). Incubation of CPSBO fortified with PE (16:0/18:1) at 60 °C for 60 min had the strongest radical scavenging activity of 85.1 ± 0.62%. Besides 2-pentyl-3,5-dibutyl-dihydropyridine, other carbonyl-amine adducts might impact the radical scavenging activity of CPSBO as well. The oxidative stability of CPSBO might be increased by promoting the formation of carbonyl-amine reaction products, such as 2-pentyl-3,5-dibutyl-dihydropyridine.