scholarly journals Tanshinone II A Relieves Adriamycin-induced Myocardial Injury in Rat Model

2015 ◽  
Vol 8 (1) ◽  
pp. 40
Author(s):  
Yu Wang ◽  
Hua Chai ◽  
Yi Lin Wang ◽  
Xian Yu Cao ◽  
Cheng Xi Wei ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Myocardial Injury ◽  
Cardiac Fibrosis ◽  
Salvia Miltiorrhiza ◽  
Antineoplastic Agent ◽  
Tanshinone Ii A ◽  
Male Wistar Rats ◽  
Effective Component ◽  
Fractional Shortening ◽  
Cellular Measurements

<p>As an effective antineoplastic agent, adriamycin (ADR) remains a use for the treatment of cancer. However, it is limited by the serous cardiotoxicity. Tanshinone II A is the main effective component of Salvia miltiorrhiza Bunge which has been used for treatment of cardiovascular diseases. The purpose of this study is to evaluate the protective effect of Tanshinone II A on adriamycin-induced myocardial injury in rat and explore the mechanism of this effect. Male Wistar rats (200 ± 20 g) were divided into three groups, control (CON) group, adriamycin (ADR) group and ADR + Tanshinone II A (TRA) group. At the end of the 4 week treatment period, cardiac function was evaluated by transthoracic echocardiography. Molecular and cellular measurements were performed in atrial muscle to examine histopathological changes, the formation of fibrosis, Inflammation and apoptosis. Cardiac dysfunction was induced by adriamycin, as indicated by significant decreases in ventricular fractional shortening and ejection fraction. This adriamycin-induced cardiac dysfunction was prevented by the treatment of Tanshinone II A. Adriamycin induced pathological changes and fibrosis, activated apoptosis (increased TUNEL index, apoptotic DNA fragmentation,and caspase-3 activity and decreased Bcl-2/Bax ratio), inflammation and suppressed phosphorylation status (eIF2α and PERK) in atrial. All these molecular and cellular alterations induced by ADR were not found in the rats treated with Tanshinone II A. These findings demonstrate clearly that Tanshinone II A protects the cardiomyocytes against the ADR-induced cardiomyopathy by preventing the activation of cardiac fibrosis and apoptosis, and the effects are probably mediated through ERS pathway.</p>

The Anticancer Drug Ellipticine is an Inducer of Rat NAD(P)H:Quinone Oxidoreductase

2007 ◽  
Vol 72 (10) ◽  
pp. 1350-1364 ◽  
Author(s):  
Marie Stiborová ◽  
Helena Dračínská ◽  
Dagmar Aimová ◽  
Petr Hodek ◽  
Jiří Hudeček ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Enzymatic Activity ◽  
Wistar Rats ◽  
Antineoplastic Agent ◽  
Chain Reaction ◽  
Potent Inducer ◽  
Male Wistar Rats ◽  
Polymerase Chain ◽  
Dt Diaphorase ◽  
Rat Livers

The antineoplastic agent ellipticine was investigated for its ability to induce the biotransformation enzyme NAD(P)H:quinone oxidoreductase (DT-diaphorase, EC 1.6.99.2) in male Wistar rats. Using the real-time polymerase chain reaction, the levels of NAD(P)H:quinone oxidoreductase mRNA were determined in livers, kidneys and lungs of rats treated intraperitoneally with ellipticine (40 mg/kg body weight) and of control (untreated) rats. Cytosolic fractions were isolated from the same tissues of control and ellipticine-treated rats and tested for NAD(P)H:quinone oxidoreductase protein expression and its enzymatic activity. The results demonstrate that ellipticine is a potent inducer of NAD(P)H:quinone oxidoreductase in rat livers and kidneys, while no induction of this enzyme was detectable in rat lungs. The increase in levels of NAD(P)H:quinone oxidoreductase mRNA correlates with the increase in expression of its protein and enzymatic activity, measured with menadione and 3-nitrobenzanthrone as substrates. The results, the identification of the potential of ellipticine to induce NAD(P)H:quinone oxidoreductase, suggest that this drug is capable of modulating biological efficiencies of the toxicants and/or drugs that are reductively metabolized by this enzyme.

scholarly journals Phytochemical and Biological Evaluation of a Newly Designed Nutraceutical Self-Nanoemulsifying Self-Nanosuspension for Protection and Treatment of Cisplatin Induced Testicular Toxicity in Male Rats

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 408
Author(s):  
Sherif R. Abdel-All ◽  
Zeinab T. Abdel Shakour ◽  
Dalia M. N. Abouhussein ◽  
Enji Reda ◽  
Thoraya F. Sallam ◽  
...  
Keyword(s):  
Antineoplastic Agent ◽  
Biological Evaluation ◽  
Particle Size Analysis ◽  
Male Rats ◽  
Size Analysis ◽  
Dilution Method ◽  
Tribulus Terrestris ◽  
Testicular Toxicity ◽  
Transmission Electron ◽  
Male Wistar Rats

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.

Abstract 87: Loss of Mir-155 Attenuates Sepsis Induced Cardiac Dysfunction

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Hui Wang ◽  
Yihua Bei ◽  
Jing Shi ◽  
Wei Sun ◽  
Peipei Huang ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Foam Cell ◽  
Cardiac Metabolism ◽  
Significant Inhibition ◽  
Gene Expressions ◽  
Over Expression ◽  
Pathological Cardiac Hypertrophy ◽  
Lps Treatment ◽  
Fractional Shortening

Objective: Sepsis induced cardiac dysfunction is featured by inflammation and metabolic repression. miR-155 is a typical multifunctional miRNA and loss of miR-155 has been shown to protect the heart from pathological cardiac hypertrophy while increased miR-155 could promote the formation of foam cell in atherogenesis. However, the role of miR-155 in sepsis induced cardiac dysfunction is unclear. Methods: E.coli lipopolysaccharide (LPS) (5mg/kg) was administered to C57BL/6 mice to create a sepsis-induced cardiac dysfunction model. Cardiac function was assessed by echocardiography 5-6 h post-LPS administration. Heart tissues were collected within 7-9 h after LPS treatment for the analysis of gene expressions. Tail vein injection of miR-155 antagomir (80mg/kg/d) or miR-155 agomirs (30mg/kg/d) for 3 consecutive days were used to decrease or increase miR-155 expressions in heart. Results: LPS induced a reduction of 15% in fractional shortening (%FS) and 25% in ejection fraction (%EF). Expression of miR-155 was increased by 2 fold in sepsis-induced cardiac dysfunction mouse model. Over-expression of miR-155 agomirs led to a decrease of 5% in FS and 10% in EF as compared to scramble controls. Aggravation of LPS induced cardiac dysfunction by miR-155 agomir was not associated with alteration in inflammation or cardiac metabolism. However, miR-155 agomir increased LPS- induced myocardium apoptosis and also elevated the ratio of Bax/Bcl-2 at the protein level. Intravenous injection of cholesterol-modified antisense oligonucleorides antagomirs of miR-155 markedly rescued the LPS induced heart failure and apoptosis. Western bloting indicated that miR-155 overexpression in vivo led to a significant inhibition of Pea15a while miR-155 knock-down caused a significant upregulation of Pea15a, indicating that Pea15a was a potential target gene of miR-155. Interestingly, plasma miR-155 levels were also found to be significantly increased in critically ill patients with sepsis compared to healthy controls. Conclusion: This study demonstrates that miR-155 regulates sepsis induced cardiac dysfunction and Pea15a is a potential targer gene of miR-155. Loss of miR-155 represents a novel therapeutic method for sepsis induced cardiac dysfunction

scholarly journals Functional dynamics of myocardial injury biomarkers production during acute isoprenaline treatment in rats

2021 ◽  
Vol 72 (2) ◽  
pp. 11-18
Author(s):  
Nina Gatarić ◽  
Ana Ilić ◽  
Dušan Todorović ◽  
Slavica Mutavdžin ◽  
Jovana Jakovljević-Uzelac ◽  
...  
Keyword(s):  
Experimental Model ◽  
Myocardial Injury ◽  
Saline Solution ◽  
Troponin T ◽  
Significant Rise ◽  
Control Group ◽  
Activity Levels ◽  
St Segment Elevation ◽  
Therapeutic Modalities ◽  
Male Wistar Rats

Introduction: Isoprenaline or isoproterenol (1-(3,4-dihydroxyphenyl)-2-isopropylaminoethanolhydrochloride; ISO), a synthetic b-adrenergic agonist, can be used to establish myocardial ischemia, cardiotoxicity, necrosis and/or an experimental model of infarction in rats. Aim: Determination of the dynamics of myocardial injury biomarkers production of aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and high-sensitive troponin T (hsTnT), with changes on electrocardiogram (ECG) parameters during the subcutaneous aplication of ISO in male Wistar rats. Material and methods: All animals (n = 23) were divided into two groups: control group (n = 11) treated with a saline solution, during two consecutive days (0,2 ml/kg b.m. daily, sc); and the ISO group (n = 12) treated with isoprenaline, during two consecutive days (85 mg/kg b.m. daily, sc). Blood was drawn from the rat tail vein in both groups, in order to determine serum activity levels of myocardial injury biomarkers, and an ECG (n = 6) was registered prior to the application, as well as 48h following the first dose of of saline solution or isoprenaline. Results: In comparison to the control group, in which no significant enzyme activities elevation (p > 0.05) nor ECG changes were registered, ISO group presented a significant rise of two clinically significant biomarkers of acute myocardial injury/myocardial infarction (AMI), CK (p = 0.05) and hsTnT (p < 0.01), as well as an ST segment elevation, with a patognomonic ECG change. Conclusion: Obtained results support previous studies, proving that isoprenaline represents an adequate experimental model for myocardial injury/AMI induction, and a "golden standard" for evaluating potential cardioprotective effects of pharmacological and non-pharmacological therapeutic modalities, with the ultimate goal of lowering the degree of lesions and improving post-infarction myocardium function.

Abstract 22: Transient Receptor Potential M2 is Involved in Secondary Myocardial Injury Induced by Nonlethal Mechanical Trauma in Rats

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Shuzhuang Li ◽  
Tingting Cao ◽  
Shuo Ma ◽  
Xiujie Li ◽  
Yue Bi ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Myocardial Injury ◽  
Transient Receptor Potential ◽  
Flufenamic Acid ◽  
Mechanical Trauma ◽  
H9c2 Cells ◽  
Sprague Dawley ◽  
Cardiac Damage ◽  
Trpm2 Channel

Background: It is an imperative task to identify the mechanisms responsible for post-traumatic secondary myocardial injury. Our previous experiments showed that mechanical trauma (MT) could induce secondary myocardial injury via oxidative stress. The transient potential receptor M2 (TRPM2) channel has emerged as an important Ca 2+ signaling mechanism in a variety of cells, contributing to cellular functions that include cytokine production, cell motility and cell death. However, the role of TRPM2 channel in nonlethal mechanical traumatic cardiac damage remains unclear. The aim of the present study was to investigate whether TRPM2 channel is involved in myocardial injury in rats subjected to nonlethal MT. Methods and results: Western blot was used to quantify TRPM2 protein levels in Ventricular myocytes of adult male Sprague Dawley rats. Up-regulation of TRPM2 channel protein was observed in the following 12h after MT. It was observed that plasma harvested from MT rats increased cytosolic Ca 2+ concentration dose-dependently in H9c2 cells. To verify the role of TRPM2 further, we administered TRPM2 blockers flufenamic acid (FFA, 100uM) and clotrimazole (CLZ, 30uM) respectively to inhibit Ca 2+ influx, which leads to attenuated intracelluar Ca 2+ overload and apoptosis induced by MT plasma in H9c2 cells. Those two TRPM2 blockers also improved cardiac dysfunction induced MT in rats. When we used TMB-8 (inhibitor of sarcoplasmic reticulum Ca 2+ store) to inhibit calcium store mobilization, intracellular Ca 2+ level, apoptosis and cardiac dysfunction were also ameliorated. However, the administration of KBR-7943 (inhibitor of Na/Ca exchanger) did not reverse the pathological process following MT. Conclusion: These results demonstrate that post-trauma pathological phenomena is associated with TRPM2 closely via a redox-sensitive signal transduction pathway (mainly via MT-initiated Ca 2+ influx, even calcium overload pathway) .We propose that treatments like blockage of TRPM2 channel-associated Ca 2+ influx and mobilization, may shed light on the novel therapeutic strategy in reducing cardiac injury and post-trauma multiple organ failure.

scholarly journals SAT-562 Angiotensin II Induces Aldosterone Synthesis in the Rat Heart Stressed by Angiotensin II

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Himangshu S Bose ◽  
Randy M Whittal ◽  
Maheshinie Rajapaksha ◽  
Brendan Marshall ◽  
Ning-Ping Wang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Rat Heart ◽  
Mitochondrial Membrane ◽  
Myocardial Injury ◽  
Cardiac Fibrosis ◽  
De Novo ◽  
Regulatory Protein ◽  
Zona Glomerulosa ◽  
Inner Mitochondrial Membrane ◽  
Native Page

Abstract Aldosterone (Aldo) causes myocardial injury and fibrosis. While most Aldo is made by the adrenal zona glomerulosa; there have been controversial reports that Aldo is also synthesized in the heart; such myocardial synthesis of Aldo might contribute to myocardial injury. We induced cardiac fibrosis in rats by infusing angiotensin II (AngII) @ 500 ng/kg/min via subcutaneous pumps. After 4 weeks, circulating corticosterone increased about 400-fold from ~29 nM to ~11 μM. Aldo synthesis in isolated mitochondria (mito) was assessed by conversion of tritiated deoxycorticosterone to Aldo; AngII infusion doubled Aldo synthesis, and this augmented synthesis was inhibited in mito from rats receiving AngII + telmisartan, which inhibits the binding of AngII to the AT1 receptor. Western blotting showed P450c11AS (Aldo synthase) was also stimulated by AngII and inhibited by telmisartan in both rat heart and H9c2 myocardial cells. 2-dimentional native PAGE and mass spectrometry showed that a 290-kDa complex on the inner mitochondrial membrane (IMM) contained P450c11AS, Tom22 (a translocase associated with the outer mitochondrial membrane, OMM), and StAR (the steroidogenic acute regulatory protein). Immunocytochemistry and transmission electron microscopy monitoring of immune-gold particles confirmed that P450c11AS, Tom22, and StAR were associated with the mito, that P450c11AS and StAR were associated with the IMM and that P450c11AS and StAR, but not Tom22, were increased by AngII. Cardiac Aldo synthesis required myocardial expression of P450c11AS, but expression of P450scc, the initial steroidogenic enzyme that converts cholesterol to pregnenolone, was undetectable, indicating the heart cannot make Aldo de novo from cholesterol. The only known action of StAR is to promote the movement of cholesterol from the OMM to IMM; nevertheless, we found that intramitochondrial StAR is required for Aldo synthesis; protein crosslinking with BS3 showed that Tom22 forms a bridge between StAR and P450c11AS. This is the first activity ascribed to intramitochondrial StAR, but the manner by which StAR promotes P450c11AS activity is unclear. As P450scc was undetectable, and circulating concentrations of corticosterone approached the Km (~28 μM) for the use of corticosterone as a substrate for P450c11AS, we suggest that cardiac P450c11AS uses circulating steroids for substrate. Thus the stressed heart produces aldosterone using a previously undescribed intramitochondrial mechanism that involves P450c11AS, Tom22 and StAR

scholarly journals Ginsenoside Re Attenuates Isoproterenol-Induced Myocardial Injury in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Quan-wei Wang ◽  
Xiao-feng Yu ◽  
Hua-li Xu ◽  
Yi-chuan Jiang ◽  
Xue-zhong Zhao ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Myocardial Injury ◽  
Troponin T ◽  
Histopathological Examination ◽  
Inflammatory Cells ◽  
Related Factor ◽  
Ginsenoside Re ◽  
Creatine Kinase Mb ◽  
Male Wistar Rats ◽  
Mda Content

Objective. Panax ginseng is widely used for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of Panax ginseng. This study aimed to investigate the protective effect of Ginsenoside Re on isoproterenol-induced myocardial injury in rats. Methods. Male Wistar rats were orally given Ginsenoside Re (5, 20 mg/kg) daily for 7 days. Isoproterenol was subcutaneously injected into the rats for two consecutive days at a dosage of 20 mg/kg/day (on 6th and 7th day). Six hours after the last isoproterenol injection, troponin T level and creatine kinase-MB (CK-MB) activity were assayed. Histopathological examination of heart tissues was performed. The levels of malondialdehyde (MDA) and glutathione (GSH) in heart tissues were measured. The nuclear factor erythroid 2-related factor 2 (Nrf2) content in nucleus and the proteins of glutathione cysteine ligase catalytic subunit (GCLC) and glutathione cysteine ligase modulatory subunit (GCLM) in heart tissues were assayed by western blotting method. Results. Treatment with Ginsenoside Re at dose of 5, 20 mg/kg reduced troponin T level and CK-MB activity of rats subjected to isoproterenol. The cardioprotective effect of Ginsenoside Re was further confirmed by histopathological examination which showed that Ginsenoside Re attenuated the necrosis and inflammatory cells infiltration. Ginsenoside Re inhibited the increase of MDA content and the decrease of GSH in heart tissues. Moreover, the Nrf2 content in nucleus and the expressions of GCLC and GCLM were significantly increased in the animals treated with Ginsenoside Re. Conclusion. These findings suggested that Ginsenoside Re possesses the property to attenuate isoproterenol-induced myocardial ischemic injury by regulating the antioxidation function in cardiomyocytes.

scholarly journals Osteopontin RNA aptamer can prevent and reverse pressure overload-induced heart failure

2017 ◽  
Vol 113 (6) ◽  
pp. 633-643 ◽  
Author(s):  
Jihe Li ◽  
Keyvan Yousefi ◽  
Wen Ding ◽  
Jayanti Singh ◽  
Lina A. Shehadeh
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Pressure Overload ◽  
Cardiomyocyte Hypertrophy ◽  
Therapeutic Effects ◽  
Rna Aptamer ◽  
Myocyte Hypertrophy

Aims Cardiac myocyte hypertrophy, the main compensatory response to chronic stress in the heart often progresses to a state of decompensation that can lead to heart failure. Osteopontin (OPN) is an effector for extracellular signalling that induces myocyte growth and fibrosis. Although increased OPN activity has been observed in stressed myocytes and fibroblasts, the detailed and long term effects of blocking OPN signalling on the heart remain poorly defined. Targeting cardiac OPN protein by an RNA aptamer may be beneficial for tuning down OPN pathologic signalling. We aimed to demonstrate the therapeutic effects of an OPN RNA aptamer on cardiac dysfunction. Methods and results In vivo, we show that in a mouse model of pressure overload, treating at the time of surgeries with an OPN aptamer prevented cardiomyocyte hypertrophy and cardiac fibrosis, blocked OPN downstream signalling (PI3K and Akt phosphorylation), reduced expression of extracellular matrix (Lum, Col3a1, Fn1) and hypertrophy (Nppa, Nppb) genes, and prevented cardiac dysfunction. Treating at two months post-surgeries with the OPN aptamer reversed cardiac dysfunction and fibrosis and myocyte hypertrophy. While genetic homozygous deletion of OPN reduced myocardial wall thickness, surprisingly cardiac function and myocardial fibrosis, specifically collagen deposition and myofibroblast infiltration, were worse compared with wild type mice at three months of pressure overload. Conclusion Taken together, these data demonstrate that tuning down cardiac OPN signalling by an OPN RNA aptamer is a novel and effective approach for preventing cardiac hypertrophy and fibrosis, improving cardiac function, and reversing pressure overload-induced heart failure.

scholarly journals Myocardial injury detected by T1 and T2 mapping on CMR predicts subsequent cancer therapy–related cardiac dysfunction in patients with breast cancer treated by epirubicin-based chemotherapy or left-sided RT

2021 ◽  
Author(s):  
Enver Tahir ◽  
Manuella Azar ◽  
Sahar Shihada ◽  
Katharina Seiffert ◽  
Yvonne Goy ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cardiac Dysfunction ◽  
Myocardial Injury ◽  
T2 Mapping ◽  
Relaxation Times ◽  
Left Ventricular ◽  
Early Prediction ◽  
Good Sensitivity ◽  
Combined Use ◽  
T1 And T2

Abstract Objectives Cancer therapy-related cardiac dysfunction (CTRCD) is a relevant clinical problem and needs early prediction. This study aimed to analyze myocardial injury using serial laboratory and cardiac magnetic resonance imaging (CMR) parameters after epirubicin-based chemotherapy compared with left-sided radiotherapy and to study their value for early prediction of CTRCD. Methods Sixty-six consecutive women (53 ± 13 years) including n = 39 with epirubicin-based chemotherapy and n = 27 with left-sided radiotherapy were prospectively studied by 3 T CMR including left ventricular (LV) mass and volumes for ejection fraction (LVEF), as well as feature-tracking with global longitudinal strain (GLS) and T1/T2 mapping. CMR was performed at baseline, at therapy completion (follow-up 1, FU1), and after 13 ± 2 months (FU2). CTRCD was defined as LVEF decline of at least 10% to < 55% or a > 15% GLS change at FU2. Results T1 and T2 increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy. CTRCD occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy. T1 at FU1 was the best single parameter to predict CTRCD with an area under the curve (AUC) of 0.712 (CI 0.587–0.816, p = 0.005) with excellent sensitivity (100%, 66–100%), but low specificity (44%, 31–58%). Combined use of increased T1 and LVEF ≤ 60% at FU1 improved AUC to 0.810 (0.695–0.896) resulting in good sensitivity (78%, 44–95%) and specificity (84%, 72–92%). Conclusion Only epirubicin-based chemotherapy, but not left-sided radiotherapy, resulted in increased T1/T2 myocardial relaxation times as a marker of myocardial injury. Combined use of CMR parameters may allow an early prediction of subsequent CTCRD. Key Points • Myocardial T1 and T2 relaxation times increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy. • Cancer therapy–related cardiac dysfunction (CTRCD) occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy. • Combined use of increased T1 and reduced LVEF had an AUC of 0.810 (0.695–0.896) to predict CTRCD with good sensitivity (78%, 44–95%) and specificity (84%, 72–92%).

scholarly journals Vidarabine, An Anti-Herpes Agent, Prevents Occlusal-Disharmony-Induced Cardiac Dysfunction in Mice

2021 ◽  
Author(s):  
Yoshio Hayakawa ◽  
Yoshiki Ohnuki ◽  
Kenji Suita ◽  
Yasumasa Mototani ◽  
Misao Ishikawa ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Oxidative Dna Damage ◽  
Cardiac Fibrosis ◽  
Control Group ◽  
Interacting Protein ◽  
Mandibular Incisor ◽  
Dependent Protein ◽  
Occlusal Disharmony

Abstract We recently reported a positive relationship between occlusal disharmony and cardiovascular disease via activation of β-adrenergic signaling in mice. Furthermore, inhibition of type 5 adenylyl cyclase (AC5), a major cardiac subtype in adults, protects the heart against oxidative stress. Here, we examined the role of AC5 in the development of occlusal-disharmony-induced cardiovascular disease in bite-opening (BO) mice, prepared by cementing a suitable appliance onto the mandibular incisor. We first examined the effects of BO treatment on cardiac function in mice treated or not treated for 2 weeks with vidarabine, which we previously identified as an inhibitor of cardiac AC. Cardiac function was significantly decreased in the BO group compared to the control group, but vidarabine ameliorated the dysfunction. Cardiac fibrosis, myocyte apoptosis and myocyte oxidative DNA damage were significantly increased in the BO group, but vidarabine blocked these changes. The BO-induced cardiac dysfunction was associated with increased phospholamban phosphorylation at threonine-17 and serine-16, as well as increased activation of the Ca2+-calmodulin-dependent protein kinase II/receptor-interacting protein 3 signaling pathway. These data suggest that AC5 inhibition with vidarabine might be a new therapeutic approach for the treatment of cardiovascular disease associated with occlusal disharmony.

Sign in / Sign up

Export Citation Format

Share Document