In a recent review published in Toxicology and Applied Pharmacologyresearchers discussed the impact of organophosphates (OP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on cardiovascular health (CVS).
Cardiotoxicity is an emerging global health problem and an important cause of mortality. OPs have been reported to induce several cardiotoxic effects, facilitating myocarditis, systolic dysfunction, arrhythmia, cardiac muscle weakening, and abnormal cardiac electrophysiology. Similar cardiac damage has been reported in SARS-CoV-2-positive patients, and therefore the synergistic effects of SARS-CoV-2 and OP compounds may increase the risks of cardiotoxicity.
About the review
In the present review, researchers discussed cardiotoxicity induced by OP and coronavirus disease 2019 (COVID-19).
SARS-CoV-2 mediated CVS impairment
SARS-CoV-2 disrupts cytokine homeostasis, redox balance, and the angiotensin-II/AT1R axis to promote CVS damage. The SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE-2), is expressed in cardiac pericytes. SARS-CoV-2-induced oxidative stress, cytokine storm, and impaired renin-angiotensin system may further escalate COVID-19-related CVS problems in patients. Increased levels of angiotensin II can cause cardiomyocyte hypertrophy.
SARS-CoV-2-induced myocytolysis fuels autoimmune responses that are triggered by the release of cellular antigens such as myosin or M2 muscarinic receptors and beta1-adrenergic receptors (β1AR). Receptor release triggers the generation of autoantibodies, such as anti-β1AR antibodies, which bind to β1AR to promote pathological cardiac remodeling and can cause dilated cardiomyopathy.
Exposure to SARS-CoV-2 can stimulate the expression of adhesion molecules, such as intracellular adhesion molecule 1 (ICAM-1), vascular CAM-1 (VCAM-1), P-selectin and E-selectin on the vascular endothelium by activating nuclear factor kappa B (NF-κB) and activating protein 1 (AP-1), promoting thrombus formation. As a result, vascular endotheliitis, heart enlargement and myocardial infarction may occur.
Cardiac damage can be identified by increased levels of troponin I and T and N-terminal pro-B-type natriuretic peptide, rapid and irregular heartbeats, markedly reduced ventricular systolic function and reduced ejection fraction, higher levels of D- dimer, fibrinogen breakdown products, longer prothrombin time, and activated partial thromboplastin time. In addition, abnormal electrocardiogram (ECG) findings such as ST elevation, prolonged Q-Tc interval, and T wave inversion have been reported.
OP-mediated CVS damage
OPs are widely used as pesticides in agricultural fields to improve crop production and meet the ever-increasing demands of crops, fruits and vegetables in the world market. They have also been used as flame retardants, plasticizers, antifoams, or antiwear agents in varnishes, hydraulic fluids, and floor polishing agents.
OP poisoning can cause CVS problems, causing myocarditis, CVS edema, arrhythmia, systolic dysfunction, infarction, and altered electrophysiology. Human serological paraoxonase 1 levels decrease in severe OR poisoning, and low serum paraoxonase activity contributes to the development of MI and coronary heart disease.
Because they are a prominent cholinesterase inhibitor, OPs can fuel arrhythmia, coronary artery disease, and congestive heart failure. Irregular pulse, torsades de pointes, right bundle branch block with atrial fibrillation, and polymorphic ventricular tachycardia have been reported. In rats, OP poisoning caused loss of striations, wide interfascicular spaces, cytoplasmic vacuolization, and myofibril detachment in cardiac muscle.
Exposure to OPs such as fenthion can cause focal myocardial damage (micronecrosis), interstitial cellular infiltrates (myocarditis), necrosis and/or apoptosis in cardiac tissues. OPs generate reactive oxygen species (ROS) and disturb the redox balance in the cellular compartment to activate death signals such as mitochondrial permeability transition pore disruption, calcium ion (Ca2+) dyshomeostasis, and adenosine triphosphate (ATP) depletion involved in cellular death. As a result, increased levels of markers of myocardial damage (creatine kinase-Mb and troponin I) combined with markers of heart failure (NT-proBNP) have been observed in OR poisoning.
Mechanistic similarities between OP poisoning and SARS-CoV-2-induced cardiotoxicity
Endothelial dysfunction is a key feature of CVS diseases. It is associated with increased levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and interferon-gamma (IFN-γ), both SARS-CoV-2 and OP compounds can cause endothelial damage. Exposure to OPs and SARS-CoV-2 promotes C-reactive protein (CRP) upregulation, ROS generation, and NF-kB pathway activation.
OP compounds and SARS-CoV-2 can cause damage to the renin-angiotensin system (RAS), decrease antioxidant levels, and increase cytosolic Ca2+ release from intracellular stores, leading to cardiac remodeling, vasoconstriction, cardiac lipid peroxidation, and damage to proteins in heart tissues. Increased diastolic blood pressure, cardiomyocyte changes, and vascular inflammation, apoptosis, and/or necrosis have been observed in both conditions, OP poisoning and COVID-19.
Overall, the review’s findings suggest that inflammation caused by SARS-CoV-2 and OP chemicals can exacerbate heart problems that can increase the risk of mortality in patients with COVID-19.