Cardiotoxic Action Research Articles

The interplay of oxidative stress, apoptotic signaling, and impaired mitochondrial function in the pyrethroid-induced cardiac injury: Alleviative role of curcumin-loaded chitosan nanoparticle

This study assessed the consequence of exposure to a pyrethroid insecticide, fenpropathrin (FPN), on the heart and the probable underlying mechanisms in rats. Moreover, the probable protective effect of curcumin-loaded chitosan nanoparticles (CMN-CNP) was evaluated. Forty male Sprague Dawley rats were distributed into four groups orally given corn oil, CMN-CNP (50 mg/kg b.wt), FPN (15 mg/kg b.wt), or CMN-CNP + FPN for 60 days. The results revealed that FPN exposure increased serum cardiac damage indicators. In addition, a substantial increase in the reactive oxygen species and malondialdehyde content but reduced enzymatic and non-enzymatic antioxidants and altered architecture was recorded in the cardiac tissue of FPN-exposed rats. Additionally, a significant down-regulation of expression of the mitochondrial complexes I–V, mitochondrial dynamics, and antioxidants-related genes but up-regulation of apoptosis-related genes was detected in the FPN-exposed group. Immunofluorescence analyses revealed higher amounts of the harmful protein 4-hydroxynonenal in the heart tissue of FPN-exposed rats. Nevertheless, the earlier disturbances were significantly rescued in the FPN + CMN-CNP treated group. Conclusively, our findings reported the cardiotoxic activity of FPN and the involvement of several mitochondrial imbalances as a probable underlying mechanism. Also, the study findings proved the efficacy of CMN-CNP in combating FPN cardiotoxic effects.

On the mechanisms of cardiotoxic action of various nanoparticles in experimental studies in vivo and in vitro

Nanoparticles are the main product of artificial technologies, and also accompany production processes in various industries. The main routes of exposure to nanoparticles are through the respiratory tract, skin and orally; therefore, most toxicological studies have focused on the lungs, liver and skin. Nanoscale particles easily penetrate the alveolar-capillary barrier and enter the bloodstream of the body. Thus, they can reach various organs, accumulate, cause toxicity, and the heart is one of the target organs.
 The study aims to search and systematize the literature data on the mechanisms of cardiotoxic action of nanoparticles of various chemical nature (elemental, elementoxide).
 The researchers conducted a literature review as part of a study of the cardiotoxic effect of nanoparticles on the body. The review is based on modern original research. When searching for literary sources, the authors used the following information databases: PubMed, Google Scholar, CyberLeninka Scientific Electronic Library, Russian Scientific Electronic Library eLibrary.Ru. In total, there were 37 original articles in the review, including 35 foreign ones, and 15 — no older than 5 years. The development of oxidative stress and an inflammatory reaction leads to the formation of cardiotoxicity of nanomaterials, which subsequently leads to necrosis and apoptosis of cells.
 Indicators of oxidative damage to lipids and DNA molecules indicate that the tissues of the heart and lungs suffer from oxidative stress not only as a result of an increase in the formation of reactive oxygen species, but also due to a malfunction of antioxidant mechanisms caused by exposure to nanoparticles.
 Studies using endothelial cells have shown that exposure to metal and metal oxide nanoparticles can promote the release of cytokines, the expression of adhesion molecules and monocyte adhesion, which are key events associated with the development of cardiovascular diseases.
 These results, combined with other in vitro data, suggest that direct contact of the cardiovascular system with metal-based nanoparticles may cause cardiovascular toxicity associated with inflammatory reactions, oxidative stress, autophagy dysfunction and endoplasmic reticulum stress. Oxidative stress induced by nanoparticles leads to apoptosis and inflammatory reactions in cardiomyocytes, as well as disrupts the integrity of mitochondrial membranes and cell organelles, leading to various heart pathologies. One of the main mechanisms of toxicity of nanoparticles of different chemical nature is oxidative stress.

The Negative Effects of Statin Drugs on Cardiomyocytes: Current Review of Laboratory and Experimental Data (Mini-Review).

Statin drugs have long been used as a key component of lipid-lowering therapy, which is necessary for the prevention and treatment of atherosclerosis and cardiovascular diseases. Many studies focus on finding and refining new effects of statin drugs. In addition to the main lipidlowering effect (blocking cholesterol synthesis), statin drugs have a number of pleiotropic effects, including negative effects. The main beneficial effects of statin drugs on the components of the cardiovascular system are: anti-ischemic, antithrombotic, anti-apoptotic, antioxidant, endothelioprotective, anti-inflammatory properties, and a number of other beneficial effects. Due to these effects, statin drugs are considered one of the main therapeutic agents for the management of patients with cardiovascular pathologies. To date, many review manuscripts have been published on the myotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity and diabetogenic effects of statins. However, there are no review manuscripts considering the negative effect of statin drugs on myocardial contractile cells (cardiomyocytes). The purpose of this review is to discuss the negative effects of statin drugs on cardiomyocytes. Special attention is paid to the cardiotoxic action of statin drugs on cardiomyocytes and the mechanisms of increased serum levels of cardiac troponins. In the process of preparing this review, a detailed analysis of laboratory and experimental data devoted to the study of the negative effects of statin drugs on cardiomyocytes was carried out. The literature search was carried out with the keywords: statin drugs, negative effects, mechanisms, cardiac troponins, oxidative stress, apoptosis. Thus, statin drugs can have a number of negative effects on cardiomyocytes, in particular, increased oxidative stress, endoplasmic reticulum stress, damage to mitochondria and intercalated discs, and inhibition of glucose transport into cardiomyocytes. Additional studies are needed to confirm and clarify the mechanisms and clinical consequences of the negative effects of statin drugs on cardiomyocytes.

Sudden cardiac death in myocarditis

According to statistics, myocarditis is one of the leading causes of sudden cardiac death (SCD) in children and young adults. The etiology of myocarditis includes infectious and non-infectious, including autoimmune diseases, as well as toxicities and hypersensitivity to various drugs or bites of insects, spiders, snakes, etc. The risk of myocarditis among patients with COVID-19 is 15.7-fold higher than that in the general population. The most common cause of death in myocarditis is heart arrhythmia, such as ventricular tachyarrhythmia, ventricular fibrillation, or severe bradycardia. Genetic predisposition, ion and metabolic disorders, mechanisms of autoimmune response, and direct cardiotoxic action in viral diseases play a role in the pathophysiology of inflammatory myocardial damage. While the majority of patients with myocarditis, who died suddenly, was asymptomatic or had few symptoms, a timely and accurate diagnosis of myocarditis seems to be an important challenge for prevention or minimization of SCD risk. Nonetheless, at present there is no convincing evidence of an association between laboratory and instrumental parameters and the SCD risk in such patients. Endomyocardial biopsy remains the "golden standard" in the diagnosis of myocarditis. Biomarkers (troponins or creatine phosphokinase) are not highly specific. The most common electrocardiographic findings in myocarditis are sinus tachycardia and nonspecific changes in the ST-T segment. The presence of Q wave, bundle branch block, Brugada syndrome, shortened or prolonged QT interval, and early ventricular repolarization are associated with an increased risk of SCD in myocarditis. Given the absence of specific echocardiographic signs of myocarditis, special attention is paid to the assessment of the size of the cardiac chambers, wall thicknesses, global and regional systolic and diastolic function of both the left and right ventricles, visualization of pericardial effusion and intracardiac thrombi. A combined cardiac magnetic resonance imaging using T2-weighted imaging and early and late gadolinium enhancement provides high diagnostic accuracy and seems to be a useful tool in the stratification of patients with suspected acute myocarditis. With the established etiology of myocarditis, specific therapy is necessary to eliminate the pathogen. It is necessary to take into account the likely arrhythmogenic effects of the drugs used in treatment. Non-steroidal anti-inflammatory drugs are generally not indicated in patients with myocarditis because they cause renal impairment and sodium retention, which can exacerbate left ventricular dysfunction and increase the risk of SCD. In the case of severe conduction disturbances and ventricular tachyarrhythmias, implantation of a pacemaker or cardioverter-defibrillator is necessary.

ANALYSIS OF DOXORUBICIN-INDUCED MITOCHONDRIAL DNA DELETIONS IN HUMAN BLOOD LEUKOCYTES AND THP-1 CELL LINE BY PCR

Doxorubicin (DOX) is an antineoplastic drug with potent cardiotoxic activity due to selective accumulation and disruption of mitochondrial functioning in cardiomyocytes. Accumulating evidence indicates that DOX can also induce genotoxic side effects in other cells. The mutagenic effects of DOX in human peripheral blood leukocytes and THP-1 leukemia cells were analyzed using PCR. It was revealed that DOX could induce deletions of different sizes and loci of mitogenomes of normal human leukocytes and THP-1 leukemic cells.

Cardiac arrhythmias and conduction disorders in acute poisoning with cardiotoxic substances

The study is devoted to the problems of poisoning by cardiotoxic diseases.
 The relevance of the study was confirmed by the analysis of literature containing the following information: during recent decades poisoning with cardiotoxic substances while providing medical care to patients has become the main cause of premature death worldwide.
 Currently, in a number of cases of poisoning several classes of compounds for medical and non-medical purposes with cardiotoxic effects can be found. The pattern of acute poisonings is highly dependent on different regions, especially in developed and developing countries, as well as in urban and coastal areas, and it also depends on socio-economic status, cultural practices, industrial and agricultural development in industry.
 The results obtained during the study show that the toxic effects of various classes of cardiotoxicants include direct (effects on the heart, blood vessels or nervous system) and indirect effects of the poison associated with the presence of metabolic disorders (hypoxia, acidosis, electrolyte disorders), and the severity of the manifestation of the condition determination of urgent toxic arrhythmias, which worsen the course of the toxic process and most often lead to a sudden death, which is an actual study of mechanisms of toxic rhythm and conduction disorders.
 The study shows changes in the electrocardiographic patterns and mechanisms of cardiotoxic action, which can be found in the structure of poisonings, their toxic doses (concentration).
 The purpose of this study was to study the features of rhythm and conduction in case of cardiotropic poisoning.
 In the course of the study the following scientific tasks were solved: changes in the electrocardiographic pattern and manifestations of cardiotoxic action, which were broadly found in the structure of poisoning, were established, and information about their toxic doses (concentrations) was summarized.
 In our opinion, the knowledge of signs of poisoning, topical symptoms, mechanisms of formation of their effects is the key to the implementation of measures to provide medical care.
 The results of the study include practical significance for the analysis and definition of various types of medical care in case of poisoning with cardiotoxic diseases of non-medical purposes.

The Impairment of Cell Metabolism by Cardiovascular Toxicity of Doxorubicin Is Reversed by Bergamot Polyphenolic Fraction Treatment in Endothelial Cells.

The beneficial effects of bergamot polyphenolic fraction (BPF) on the mitochondrial bioenergetics of porcine aortic endothelial cells (pAECs) were verified under the cardiotoxic action of doxorubicin (DOX). The cell viability of pAECs treated for 24 h with different concentrations of DOX was reduced by 50%, but the negative effect of DOX was reversed in the presence of increasing doses of BPF (100 µg/mL and 200 µg/mL BPF). An analysis of the protective effect of BPF on the toxic action of DOX was also carried out on cell respiration. We observed the inhibition of the mitochondrial activity at 10 µM DOX, which was not restored by 200 µg/mL BPF. Conversely, the decrease in basal respiration and ATP production caused by 0.5 or 1.0 µM DOX were improved in the presence of 100 or 200 µg/mL BPF, respectively. After 24 h of cell recovery with 100 µg/mL or 200 µg/mL BPF on pAECs treated with 0.5 µM or 1.0 µM DOX, respectively, the mitochondrial parameters of oxidative metabolism impaired by DOX were re-boosted.

Modern approach to perioperative pain relief using various modern methods and anesthetics

Adequate postoperative analgesia remains unresolved problem of the acute pain treatment. In spite of wide choice of different groups of analgesics, epidural analgesia is the most adequate and efficient method of the postoperative analgesia. Continuous epidural analgesia is broadly used for postoperative pain relief. Such approach has own advantage over periodic administration of anesthetics into epidural space. These positive effects include constant level of the good pain relief, possibility of patients to participate in process of the pain management, reduction of probability of infectious complications in accordance with the use of epidurals and others. Besides, continues epidural infusion vastly reduces the load on medical stuff. Using electronic pumps for prolonged epidural analgesia has its own advantages and disadvantages. Disposable infusion pumps have not these disadvantages, in contrast of electric infusion pumps. Local anesthetics except their main effect possess anti-inflammatory action. This effect is not only under low plasma concentration, which does not possess cardiotoxic action. Such low plasma concentrations are possible to reach only under prolonged epidural infusion. At present, for prolonged epidural infusion bupivacaine and ropivacaine are most often used. Ropivacain possesses beside advantage over other local anesthetics. Ropivacaine is less cardiotoxic, than bupivacaine.

Insights into the Cardiotoxic Effects of Veratrum Lobelianum Alkaloids: Pilot Study.

Jervine, protoveratrine A (proA), and protoveratrine B (proB) are Veratrum alkaloids that are presented in some remedies obtained from Veratrum lobelianum, such as Veratrum aqua. This paper reports on a single-center pilot cardiotoxic mechanism study of jervine, proA, and proB in case series. The molecular aspects were studied via molecular dynamic simulation, molecular docking with cardiac sodium channel NaV1.5, and machine learning-based structure–activity relationship modeling. HPLC-MS/MS method in combination with clinical events were used to analyze Veratrum alkaloid cardiotoxicity in patients. Jervine demonstrates the highest docking score (−10.8 kcal/mol), logP value (4.188), and pKa value (9.64) compared with proA and proB. Also, this compound is characterized by the lowest calculated IC50. In general, all three analyzed alkaloids show the affinity to NaV1.5 that highly likely results in cardiotoxic action. The clinical data of seven cases of intoxication by Veratrum aqua confirms the results of molecular modeling. Patients exhibited nausea, muscle weakness, bradycardia, and arterial hypotension. The association between alkaloid concentrations in blood and urine and severity of patient condition is described. These experiments, while primary, confirmed that jervine, proA, and proB contribute to cardiotoxicity by NaV1.5 inhibition.

Novel HM12, A Selective Inhibitor of L‐/T‐type Calcium Channels, Averts Doxorubicin Cardiotoxicity in Male Wistar Rats

Doxorubicin is a cytotoxic anthracycline anticancer drug that is limited by its cardiotoxic action. This study sought to investigate the cardiopreventive potential of HM12, a 1,4‐dihydropyridine (DHP) derivative (CCB) against doxorubicin induced cardiotoxicity in male Wistar rats. HM12 was synthesized as a DHP‐based hexahydroquinoline derivative (2‐[(2‐methylacryloyl)oxy]ethyl 4‐(3,5‐dibromo‐2‐hydro[1]xyphenyl)‐2,6,6‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate) according to the modified Hantzsch reaction via condensation reactions under microwave irradiation. HM12 structure was confirmed using infrared, proton, and carbon‐13 nuclear magnetic resonance, and mass spectra. The CCB activity was evaluated using whole‐cell patch‐clamp assays. Further, fourty‐eight adult male Wistar rats were divided into eight groups of 6/group and received distilled water saline; doxorubicin (DOX, 20 mg/kg, i.p.), HM12 lower (HM12LD) or upper (HM12UD) dose (5 or 20 mg/kg, p.o.), nifedipine (NFD, 20 mg/kg), and their combinations. All rats were sacrificed 24 h after the last administration and changes in blood pressure (BP), heart rate (HR), biochemical, oxidative stress indices, and heart histology were assessed. DOX cardiotoxicity produced spontaneous increased (p<0.05) BP (baseline 106.5/84 mmHg (day 1) versus 170/173.5 mm/Hg (59.6/72%, day 6) and 173.5/167 mmHg (98.8/69.1%, day 7) with altered HR (baseline 99 beats per minutes versus 167.5 bpm (69.1%, day 7). Also, DOX‐treated rats showed a significant increase in tumor necrosis factor‐α (TNF‐α), c‐reactive protein (CRP), and lactate dehydrogenase (LDH). This was accompanied by an increase (p<0.05) in cardiac malondialdehyde (MDAc) and decreased reduced glutathione (GSHc) levels, and activities of catalase (CATc) and superoxide dismutase (SODc). However, HM12UD + DOX had changes BP (baseline 106.5/96 mmHg (day 1) versus 181/179.5 mmHg (70.1/87%, day 6) versus 135/127 mmHg (26.8/32.3%, day 7) with HR (baseline 93.5 beats per minutes versus 164.5 bpm (75.9%, day 6) to 127 bpm (35.8%, day 7). Also, HM12UD was effective against IL‐6, CRP, LDH but not TNF‐α. Further, HM12UD significantly reversed DOX‐induced MDAc by elevating antioxidants GSHc levels as well as activities of CATc and SODs in the treated animals. Additionally, HM12UD averted histopathological changes observed in the rat heart due to DOX intoxication. Overall, the present study conferred new evidence on the protective effects CCBs, in particular, HM12 on DOX‐induced cardiotoxicity, oxidative stress, tumor biomarkers, and cardiac histological changes in rats.

New pyrimidine/thiazole hybrids endowed with analgesic, anti-inflammatory, and lower cardiotoxic activities: Design, synthesis, and COX-2/sEH dual inhibition.

Some cyclooxygenase (COX)-2 selective medications were withdrawn from the market just a few years after their production due to cardiovascular side effects. In this study, a new series of pyrimidine/thiazole hybrids 7a-p was synthesized as selective COX-2/soluble epoxide hydrolase (sEH) inhibitors with analgesic and anti-inflammatory effects, and lower cardiotoxicity effects. The target compounds were synthesized and in vitro tested against COX-1, COX-2, and sEH enzymes. Hybrids 7j, 7k, and 7i showed the greatest COX-2-inhibitory activity and were discovered to be the most potent dual COX-2/sEH inhibitors. In vivo tests revealed that these hybrids were the most active analgesic/anti-inflammatory agents, with improved ulcerogenic and cardioprotective properties. Finally, the most active dual inhibitors were docked into COX-2/sEH active regions to explain their binding mechanisms.

Cardiotoxic Effect of Aqueous Extract of Some Indigenous Plants on American Cockroach: Periplaneta Americana Linn

Abstract: The Cardiotoxic effect of aqueous extract of some indigenous plants is evaluated on American cockroach, Periplaneta Americana Linn as an experimental animal in laboratory conditions. Toxicity of plant extract was determined in terms of LD50 value in the cockroach by tropical application. However, the Cardiotoxic activity was found to be higher in experimental animals as compared to control on exposure to plant extracts and it was dose dependent. Among the plants evaluated Balanites roxburghii Planch, Cestrum nocturnum Linn, Nicotiana tabecum Linn and Sapindus trifoliatus Linn showed highly Cardiotoxic activity causes significant reduction in heart rate. Whereas, Azadirachta indica A. Juss extract shows least activity than remaining experimental plants. This result therefore seems to support the claim that the plant extract contain saponin and glycoside as an active ingredients in them. Keywords: Cardiotoxic, American cockroach, Plant extract, Heart rate, Dose dependent.

PROSPECTIVE INTERVENTIONAL STUDY OF COMPARISON BETWEEN EPIDURALANAESTHESIA PLAIN 0.75% ROPIVACAINE AND 0.75% ROPIVACAINE WITH DEXMEDITOMIDINE IN LOWER ABDOMINAL AND LOWER LIMB SURGERIES

1.1 AIMS: The aim of the study is to identify the benets of adding Dexmedetomidine 0.6mcg/kg to Ropivacaine 0.75% for epidural analgesia for surgeries involving lower abdomen and lower limb, and to observe the onset of sensory and motor blockade, duration of analgesia, and sedation score. 1.2 BACKGROUND: Studies indicate that regional anesthesia has numerous advantages for lower abdominal and lower limb surgeries when compares to general anesthesia. Hence distinct varieties of regional anesthetics are being used for epidural anesthesia. When looking into regional anesthesia it was learned that ropivacaine was the preferred regional anesthesia for its long-acting effect and lower the cardiotoxic action in comparison to Dexmedetomidine. Whereas in comparison to ropivacaine, Dexmedetomidine has an additional effect, along with prolonging the action and sedative effect its neuroprotective effect is mediated by activation of alpha 2 adrenergic receptor subtype [2]. After looking at the individual benets of Ropivacaine, and Dexmedetomidine, this study aims to see the potential benets of the combined effects of these two drugs. 1.3 OBJECTIVE: To study the onset of action, duration of sensory and motor blockade, and any hemodynamic variations, level of sensory and motor blockade. 1.4 METHODS: The Patients were randomly allocated to two groups and each group consisted of 50 patients 1) Group R -15ml of 0.75% Ropivacaine 2) Group RD- 15ml of 0.75% Ropivacaine + 0.6µg/kg of dexmedetomidine. 1.5 RESULTS:The study concluded that adding dexmedetomidine as an adjuvant to Ropivacaine for epidural anesthesia reduced the time to onset of action, and increased the duration of sensory blockade. Patients were calm, with sedation scores of 3 and 4 in RD Group, and did not require extra sedation. Patients were hemodynamically stable in both groups.

Taurine blunts doxorubicin cardiotoxicity: chronic and acute effects

Abstract Funding Acknowledgements Type of funding sources: None. Aim. To study the functional statement of the isolated heart inherent to doxorubicin cardiotoxicity under the chronic and acute action of taurine. Material and methods. Doxorubicin (Dx) cardiotoxicity manifested by heart failure development was reproduced classically by anthracycline i/p administration in rats in cumulative dose of 16 mg/kg (4 mg/kg four times during 2 weeks) – Dx series. Series with chronic action of taurine (Tr) included rats receiving this aminoacid daily per os during Dx administration (100 mg/kg) – Dx + Tr series. Rats of both series were sacrificed by euthanasia and the isolated heart was perfused by Krebs solution according to Langendorff (isovolumic heart) and Neely-Rovetto (working heart) methods in conditions of diverse hemodynamic and neuroendocrine efforts applying. Acute action of taurine was studied during its infusion in the perfusate of isolated hearts in final concentration of 40 µM. The hearts of intact rats constituted the control series. Results. Chronic action of taurine has identified certain important functional benefits, the most important being underlined beneath. The first, taurine reversed the negative inotropic effect of isolated heart on endothelin-1 (ET-1) action (10-7 M), detected in Dx series and manifested by both systolic pressure of left ventricle (LV) and cardiac output fall by about 9,1%. Taurine assured increase of these indices during ET-1 stimulation. The second, Tr notably improved both isovolumic relaxation and contraction of myocardium exhibited by significant enhancement of Veragut index (118,6 ± 9,6 vs 94,8 ± 6,5 1/sec), +dP/dPmax (8389 ± 445 vs 7216 ± 363 mm Hg/sec) and -dP/dTmax (7526 ± 378 vs 5684 ± 322 mm Hg/sec) during efforts with volume and resistance. The third, Tr significantly decreased LV end diastolic pressure (LVSDP) when coronary pressure of isovolumic heart elevated by 50% (from 80 up to 120 cm H20 column): 16,2 ± 1,2 vs 18,8 ± 1,4 mm Hg. Acute Tr action manifested by: (i) significant LVSDP diminution during 30 min of ischemia (52,4 ± 3,1 vs 63,7 ± 4,4 mm Hg) and on 45th min of reperfusion (18,3 ± 1,3 vs 22,8 ± 1,4 mm Hg), (ii) increased time of LV extrasystole appearance when the glucose content of Krebs solution was reduced by 50% (28,6 ± 2,8 vs 22,5 ± 2,4 min), and (iii) increased time of LV tachyarrhythmia appearance when the potassium content of Krebs solution raised up to 6,5 meq/L (9,2 ± 0,5 vs 6,9 ± 0,3 min). Conclusion. Taurine, a natural calcium modulator of the heart, notably improves functional reserves of the myocardium exposed to cardiotoxic action of Dx, and could be seen as a relevant remedy of primary and secondary prophylaxis of Dx induced heart failure in oncologic patients.

Molecular Mechanisms of the Cardiotoxic Action of Anthracycline Antibiotics and Statin-Induced Cytoprotective Reactions of Cardiomyocytes

Molecular Mechanisms of the Cardiotoxic Action of Anthracycline Antibiotics and Statin-Induced Cytoprotective Reactions of Cardiomyocytes

Differential Effects of p-Coumaric Acid in relieving Doxorubicin induced Cardiotoxicity in Solid Tumour Bearing and Non-tumor Bearing Mice

The cardioprotective potential of p-coumaric acid (pCA) against Doxorubicin (Dox)-mediated cardiotoxicity in normal animals has been previously documented. The present study sought to examine the effect of pCA on the cardiotoxic and anti-tumor activity of Dox in non-tumor vs. Daltons Lymphoma Ascites (DLA) induced solid tumor model. Male Swiss Albino mice were pretreated and co-treated with pCA (100 mg/kg b.w.), after which Dox (16 mg/kg b.w. cumulative) was administered for a period of 28 days. Levels of serum cardiac diagnostic markers, lipid peroxidation products, and liver marker enzymes were significantly increased (P<0.05) in the Dox only treated groups. Partial restoration of the antioxidant system in the pCA pre/co-treated groups was observed. Cardiac damage was elevated in the Dox only tumor group; evident from changes in the heart/body weight ratio, haematological and biochemical analyses. Dox treated groups showed a significant reduction in tumor progression. pCA treatment did not appear to impede/enhance the efficacy of Dox-mediated anti-tumor activity in the tumor supergroup. This study leads us to conclude that pCA can be explored as a potent molecule to combat Dox-induced cardiotoxicity by the virtue of its proven antioxidant properties with no interference in the anti-tumor activity of Dox at the given dose.

Cardiotoxic Effects of Micrurus surinamensis (Cuvier, 1817) Snake Venom

Micrurus surinamensis is a coral snake from the Elapidae family of wide distribution in Amazonia Forest. Its venom contains neurotoxins that induce muscular and respiratory paralysis; however, its cardiovascular action is not yet characterized. The aim of this study was to investigate the cardiotoxic effects caused by M. surinamensis poisoning in rodents. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6) named as control and envenomed. The control group received 0.2ml of PBS/BSA via intramuscular injection (IM), while envenomed animals received 0.75µg of venom per g of body weight, also via IM. Electrocardiographic examination (ECG) and biochemical serum tests were conducted before and 2h after inoculation. ECG of the envenomed animals revealed severe progressive arrhythmias including atrioventricular block, supraventricular, and ventricular extrasystoles. Serum biochemistry showed significant increase in CK, CK-MB, and LDH enzymes corroborating the skeletal and cardiac muscle damage. Myonecrosis and degeneration were observed in both skeletal and heart muscle; nevertheless, transmission electron microscopy revealed cardiac muscle fibers fragmentation. In conclusion, M. surinamensis venom has a potent cardiotoxic activity eliciting arrhythmogenic effects and heart damage after only 2h of envenomation.

Forensic characteristics of the cardio-toxic effect of organophosphorus compounds

Objective - to identify the morphological equivalents of the cardiotoxic action of organophosphate poisoning. It was studied 110 fatal organophosphate poisonings in toxicogenic and somatogenic stages. The study of the heart was a comprehensive in term of clinical, biochemical, histological, micromorphometric, histochemical and histoenzymological approaches. We have identified a complex of deep metabolic disorders and necrobiotic changes in the heart muscle and the level of cholinesterase activity inhibition in the cholinergic structures of the heart in the toxicogenic and somatogenic stages of fatal organophosphate poisoning.

Platelets and Their Role in the Pathogenesis of Cardiovascular Events in Patients With Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) remains an important cause of morbidity and mortality throughout the world with much recent and ongoing research focused on the occurrence of cardiovascular events (CVEs) during the infection, which are associated with adverse short-term and long-term survival. Much of the research directed at unraveling the pathogenesis of these events has been undertaken in the settings of experimental and clinical CAP caused by the dangerous, bacterial respiratory pathogen, Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of CAP. Studies of this type have revealed that although platelets play an important role in host defense against infection, there is also increasing recognition that hyperactivation of these cells contributes to a pro-inflammatory, prothrombotic systemic milieu that contributes to the etiology of CVEs. In the case of the pneumococcus, platelet-driven myocardial damage and dysfunction is exacerbated by the direct cardiotoxic actions of pneumolysin, a major pore-forming toxin of this pathogen, which also acts as potent activator of platelets. This review is focused on the role of platelets in host defense against infection, including pneumococcal infection in particular, and reviews the current literature describing the potential mechanisms by which platelet activation contributes to cardiovascular complications in CAP. This is preceded by an evaluation of the burden of pneumococcal infection in CAP, the clinical features and putative pathogenic mechanisms of the CVE, and concludes with an evaluation of the potential utility of the anti-platelet activity of macrolides and various adjunctive therapies.

Molecular mechanisms of the cardiotoxic action of anthracycline antibiotics and statin-induced cytoprotective reactions of cardiomyocytes

The manifestation of the side cardiotoxic effect of anthracycline antibiotics limits their use in the treatment of malignant processes in some patients. The review analyzes the main causes of the susceptibility of cardiomyocytes to the damaging effect of anthracyclines, primarily associated with an increase in the processes of free radical oxidation. Currently, research is widely carried out to find ways to reduce anthracycline cardiotoxicity, in particular, the use of cardioprotective agents in the complex treatment of tumors. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to improve the function and metabolism of the cardiovascular system under various pathological impacts, therefore, it is proposed to use them to reduce cardiotoxic complications of chemotherapy. Statins exhibit direct (hypolipidemic) and pleiotropic effects due to the blockade of mevalonic acid synthesis and downward biochemical cascades that determine their cardioprotective properties. The main point of intersection of the pharmacological activity of anthracyclines and statins is the ability of both to regulate the functioning of small GTPase from the Rho family, and their effect in this regard is the opposite. The influence of statins on the modification and membrane dislocation of Rho proteins mediates the indirect antioxidant, anti-inflammatory, endothelioprotective, antiapoptotic effect. The mechanism of statin inhibition of doxorubicin blockade of the DNA-topoisomerase complex, which may be important in preventing cardiotoxic damage during chemotherapy, is discussed. At the same time, it should be noted that the use of statins can be accompanied by adverse side effects: a provocation of increased insulin resistance and glucose tolerance, which often causes them to be canceled in patients with impaired carbohydrate metabolism, so further studies are needed here. The review also analyzes data on the antitumor effect of statins, their ability to sensitize the tumor to treatment with cytostatic drug. It has been shown that the relationship between anthracycline antibiotics and statins is characterized not only by antagonism, but also in some cases by synergism. Despite some adverse effects, statins are one of the most promising cardio- and vasoprotectors for use in anthracycline cardiomyopathy.