Effective Antioxidant activity of Phytic acid Prevents Isoproterenol-Induced Myocardial Infarction in Albino wistar Rats

This study aimed to evaluate the preventive effect of phytic acid on cardiac markers, blood glucose, total proteins, albumin/globulin (A/G) ratio, serum uric acid, serum iron, and plasma iron binding capacity in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for 2 days showed a significant increase in the degrees of cardiac troponin T (cTnT), intensity of the bands of lactate dehydrogenase (LDH)-isoenzyme (LDH1 and LDH2) and the activities of cardiac marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) in serum with subsequent decrease in the activities of CK, LDH, AST and ALT in the heart. ISO-induced rats showed a significant increase in blood glucose, serum uric acid, serum iron and a decrease in the levels of total proteins, A/G ratio and iron binding capacity. Pretreatment with phytic acid (25 and 50 mg/kg) daily for a period of 56 days positively altered the levels of cTnT, intensity of the bands of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, and other biochemical parameters. Thus, phytic acid possess cardioprotective effect in ISO-induced oxidative stress in rats.

Oxidative stress in myocardial infarction-does it correlate with the cardiac marker troponin?

A myocardial infarction (MI), often known as a heart attack, occurs when blood supply to a region of the heart is reduced or stopped, resulting in heart muscle damage. One of the elemental mechanisms responsible for the development of myocardial infarction is oxidative stress. The study aims to assess the Oxidative stress and Troponin I levels in patients with myocardial infarction (MI) and compare them with the level of these parameters in healthy controls. An attempt has been made to find if there is any correlation between oxidative stress and Troponin I levels in patients with myocardial infarction.The Cardiac marker Troponin I and the marker of oxidative stress malondialdehyde were estimated in 30 patients with myocardial infarction and 30 healthy individuals who acted as controls. A statistically significant difference was observed between Troponin I and MDA in patients with MI as compared with controls. A significant positive correlation was also observed between MDA and Troponin I levels. In our study there wasa significant positive correlation between oxidative stress and Troponin I. Further studies with a larger number of subjects will be needed to find if oxidative stress plays a role in the pathogenesis of myocardial infarction.

Nerolidol Attenuates Oxidative Stress, Inflammation, and Apoptosis by Modulating Nrf2/MAPK Signaling Pathways in Doxorubicin-Induced Acute Cardiotoxicity in Rats

The clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic drug, is often limited by its cardiotoxic effects. Thus, for improving usage of DOX, the aim of this study was to assess the cardioprotective effects of nerolidol (NERO) in a rat model of DOX-induced acute cardiotoxicity and examine underlying molecular mechanisms that contribute to these effects. To induce acute cardiotoxicity male albino Wistar rats were injected with single dose intraperitoneal DOX (12.5 mg/kg). The rats were treated with NERO (50 mg/kg, orally) for five days. DOX-injected rats showed elevated levels of cardiac marker enzymes and enhanced oxidative stress markers along with altered Nrf2/Keap1/HO-1 signaling pathways. DOX administration also induced the activation of NF-κB/MAPK signaling and increased the levels and expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) as well as expression of inflammatory mediators (iNOS and COX-2) in the heart. DOX also triggered DNA damage and apoptotic cell death in the myocardium. Additionally, histological studies revealed structural alterations of the myocardium. NERO treatment exhibited protection against the deleterious results of DOX on myocardium, as evidenced by the restoration of altered biochemical parameters, mitigated oxidative stress, inflammation, and apoptosis. The findings of the present study demonstrate that NERO provides cardioprotective effects against DOX-induced acute cardiotoxicity attributed to its potent antioxidant, anti-inflammatory, and antiapoptotic activities through modulating cellular signaling pathways.

Diagnostic Value of Heart-type Fatty Acid Binding Protein in Group of Patients with NSTEMI at the Time of Application for Medical Care

The relevance of the early detection of myocardial necrosis is due to the difficulties of differential diagnosis in the first hours of the development of acute coronary syndrome. Therefore, the doctors of the first contact, as before, are interested in an early cardiac marker and the presence of tests based on it. Heart fatty acid binding protein (h-FABP) is a cardiac marker that increases in the blood to diagnostic values after just one hour from the beginning of clinical manifestations. The objective: to determine the diagnostic value of heart fatty acid binding protein in group of patients with NSTEMI. Materials and methods. We examined 280 patients with STEMI, 91 patients with NSTEMI, 76 with stable angina pectoris. Blood samples were taken from all patients at the first contact to determine troponin I, a heart fatty acid binding protein and CPK-MB. Patients with NSTEMI were divided into three subgroups: the first – up to 3 hours from the onset of symptoms, the second – from 3 to 6, the third from 6 to 12. The level of heart fatty acid binding protein in plasma was determined by enzyme immunoassay. Results. The early detection of AMI in people visiting primary care doctors with chest pain continues to be a challenge. Undoubtedly, cardiac troponins are the “gold standard” for the diagnosis of AMI, but early detection of these can give a negative result. The results of the studies show a high diagnostic efficacy of h-FABP in the early diagnosis of AMI, and it is superior in sensitivity (in the first hours from the onset of the disease) to cardiac troponins. So, for example, in the subgroup of patients with the onset of symptom manifestation up to 3 hours for h-FABP with a cut-off >0,48 ng/ml, the sensitivity was 92.7 % and specificity was 97,3 % (AUC=0,99; 95 % CI AUC 0,942–0,998). In the same subgroup, troponin I had a specificity of 22,0 %, with cut off >0,84 ng/ml (AUC=0,71; 95 % CI AUC 0,615–0,787). Conclusions. The level of cardiac protein that binds fatty acids is significantly increased in patients with acute myocardial infarction compared with stable coronary heart disease.

Cardiac progenitors auto-regulate second heart field cell fate via Wnt secretion

Proper heart formation requires coordinated development of two anatomically distinct groups of cells - the first and second heart fields (FHF and SHF). Given that congenital heart defects are often restricted to derivatives of the FHF or SHF, it is crucial to understand the mechanisms controlling their development. Wnt signaling has previously been implicated in SHF proliferation; however, the source of Wnts remains unknown. Through comparative gene analysis, we found upregulation of Wnts and Wnt receptor/target genes in the FHF and SHF, respectively, raising the possibility that early cardiac progenitors may secrete Wnts to influence SHF cell fate. To probe this further, we deleted Wntless (Wls), a gene required for Wnt ligand secretion, in various populations of precardiac cells. Deletion of Wls in Mesp1+ cells resulted in formation of a single chamber heart with left ventricle identity, implying compromised SHF development. This phenotype was recapitulated by deleting Wls in cells expressing Islet1, a pan-cardiac marker. Similarly, Wls deletion in cells expressing Nkx2.5, a later-expressed pan-cardiac marker, resulted in hypoplastic right ventricle, a structure derived from the SHF. However, no developmental defects were observed when deleting Wls in SHF progenitors. To gain mechanistic insights, we isolated Mesp1-lineage cells from developing embryos and performed single-cell RNA-sequencing. Our comprehensive single cell transcriptome analysis revealed that Wls deletion dysregulates developmental trajectories of both anterior and posterior SHF cells, marked by impaired proliferation and premature differentiation. Together, these results demonstrate a critical role of local precardiac mesodermal Wnts in SHF fate decision, providing fundamental insights into understanding heart field development and chamber formation.Significance StatementThere is significant interest in understanding the mechanisms underlying heart formation to develop treatments and cures for patients suffering from congenital heart disease. In particular, we were interested in the intricacies of first (FHF) and second heart field (SHF) development, as many congenital heart defects present with heart field-specific etiologies. Here, we uncovered a novel relationship between specified cardiac progenitor cells and second heart field progenitors. Through genetic manipulation of Wnt secretion in developing mouse embryos, we identified a population of cardiac progenitor cells that acts as a local source of Wnts which are necessary for proper SHF development. Our single cell transcriptomic analysis of developing anterior mesoderm showed cardiac progenitor-secreted Wnts function through regulation of differentiation and proliferation among SHF progenitors. Thus, this study provides insight into the source and timing of Wnts required for SHF development, and points to the crucial role of co-developing cell populations in heart development.