scholarly journals Oxidative stress and inflammation: determinants of anthracycline cardiotoxicity and possible therapeutic targets

2020 ◽  
Author(s):  
Iacopo Fabiani ◽  
Alberto Aimo ◽  
Chrysanthos Grigoratos ◽  
Vincenzo Castiglione ◽  
Francesco Gentile ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Imaging Techniques ◽  
Significant Risk ◽  
Left Ventricular ◽  
Cardiac Damage ◽  
Anthracycline Cardiotoxicity ◽  
Screening Strategies ◽  
Dose Dependent

AbstractChemotherapy with anthracycline-based regimens remains a cornerstone of treatment of many solid and blood tumors but is associated with a significant risk of cardiotoxicity, which can manifest as asymptomatic left ventricular dysfunction or overt heart failure. These effects are typically dose-dependent and cumulative and may require appropriate screening strategies and cardioprotective therapies in order to minimize changes to anticancer regimens or even their discontinuation. Our current understanding of cardiac damage by anthracyclines includes a central role of oxidative stress and inflammation. The identification of these processes through circulating biomarkers or imaging techniques might then be helpful for early diagnosis and risk stratification. Furthermore, therapeutic strategies relieving oxidative stress and inflammation hold promise to prevent heart failure development or at least to mitigate cardiac damage, although further evidence is needed on their efficacy, either alone or as part of combination therapies with neurohormonal antagonists, which are the current adopted standard.

Role of oxidative stress in left ventricular remodeling and heart failure after myocardial infarction

1999 ◽  
Vol 5 (3) ◽  
pp. 79
Author(s):  
Shintaro Kinugawa ◽  
Hiroyuki Tsutsui ◽  
Tomomi Ide ◽  
Hideo Ustumi ◽  
Nobuhiro Suematsu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular

Abstract 1271: IKKβ/NF-κB Pathway Protects Hearts from Hemodynamic Stress Mediated through Regulating MnSOD Expression

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Shungo Hikoso ◽  
Kinya Otsu ◽  
Osamu Yamaguchi ◽  
Toshihiro Takeda ◽  
Masayuki Taniike ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Negative Regulator ◽  
Iκb Kinase ◽  
Jnk Activation

Objectives: We have previously reported that NF-κB contributes to GPCR agonist-induced hypertrophy in cultured cardiomyocytes. However, the in vivo role of this pathway in the pathogenesis of cardiac remodeling remains to be elucidated. Although IκB kinase β (IKKβ)/NF-κB pathway is a major negative regulator of cell death, it can sensitize cells to death-inducing stimuli in some instances, thus it can be either anti- or pro-apoptotic. In this study, we aimed to clarify the role of IKKβ/NF-κB signaling in cardiac remodeling using cardiac-specific IKKβ deficient mice. Methods and Results: We crossed mice bearing an IKK β flox allele with mice expressing the Cre recombinase under the control of the myosin light chain 2v promoter ( MLC2v-Cre +/− ) to generate IKK β flox/flox ; MLC2v-Cre +/− mice (conditional knockout:CKO). Then, CKO mice (n=14) and control littermates bearing IKK β flox/flox (CTRL, n=14) were subjected to pressure overload by means of transverse aortic constriction (TAC). EMSA analysis revealed NF-κB DNA binding activity after TAC had attenuated in CKO hearts. One week after TAC, echocardiography showed significantly lower left ventricular fractional shortening (26.9±2.7% vs. 41.4±0.9%, p<0.01), and higher left ventricular end-diastolic dimension (4.02±0.14 mm vs. 3.47±0.08 mm, p<0.01) and lung weight/body weight ratio (11.1±1.4 vs. 5.5±0.1, p<0.01) in CKO mice compared with CTRL mice, indicating the development of heart failure in CKO mice. Number of apoptotic cells had increased in CKO hearts after TAC, suggesting that the enhanced apoptosis is a cause for heart failure. The expression levels of MnSOD mRNA and protein after TAC, which is one of NF-κB target genes, were significantly lower in CKO than those in CTRL mice. As a consequence, oxidative stress and JNK activation in CKO hearts after TAC had significantly increased compared with those in CTRL heart, suggesting that increased oxidative stress and enhanced JNK activity resulted in cardiomyocyte apoptosis in CKO hearts. Conclusion: These results show that IKKβ/NF-κB pathway in cardiomyocyte plays a protective role mediated through attenuation of oxidative stress and JNK activation in response to pressure overload.

scholarly journals Modulation of MAPK and NF-κB Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats

2016 ◽  
Vol 39 (1) ◽  
pp. 371-384 ◽  
Author(s):  
Paula F. Martinez ◽  
Camila Bonomo ◽  
Daniele M. Guizoni ◽  
Silvio A. Oliveira Junior ◽  
Ricardo L. Damatto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Signaling Pathways ◽  
Soleus Muscle ◽  
Intracellular Signaling ◽  
Left Ventricular ◽  
Skeletal Myopathy ◽  
Antioxidant Agents ◽  
Muscle Changes

Background/Aims: Although increased oxidative stress plays a role in heart failure (HF)-induced skeletal myopathy, signaling pathways involved in muscle changes and the role of antioxidant agents have been poorly addressed. We evaluated the effects of N-acetylcysteine (NAC) on intracellular signaling pathways potentially modulated by oxidative stress in soleus muscle from HF rats. Methods and Results: Four months after surgery, rats were assigned to Sham, myocardial infarction (MI)-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. Oxidative stress was evaluated in serum and soleus muscle; malondialdehyde was higher in MI-C than Sham and did not differ between MI-C and MI-NAC. Oxidized glutathione concentration in soleus muscle was similar in Sham and MI-C, and lower in MI-NAC than MI-C (Sham 0.168 ± 0.056; MI-C 0.223 ± 0.073; MI-NAC 0.136 ± 0.023 nmol/mg tissue; p = 0.014). Western blot showed increased p-JNK and decreased p38, ERK1/2, and p-ERK1/2 in infarcted rats. NAC restored ERK1/2. NF-κB p65 subunit was reduced; p-Ser276 in p65 and IκB was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-κB p65 subunit, but decreased p-Ser276 and p-Ser536. Conclusion: N-acetylcysteine modulates MAPK and NF-κB signaling pathways in soleus muscle of HF rats.

scholarly journals Az oxidatív stressz szerepe az amiodarontoxicitásban, valamint a hypertoniás betegek balkamra-diszfunkciójában és a megőrzött ejekciós frakciójú szívelégtelenségben

2015 ◽  
Vol 156 (47) ◽  
pp. 1921-1925
Author(s):  
András Vereckei
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Antiarrhythmic Action ◽  
Preserved Ejection Fraction ◽  
Widespread Application

The author briefly summarizes his scientific work investigating the role of oxidative stress in cardiovascular disorders. Using in vitro biochemical, biophysical and in vivo animal research it was found that oxidative stress plays a substantial role in the pathogenesis of amiodarone toxicity and antioxidants co-administered with amiodarone exert at least partial protective effect on amiodarone toxicity, while antioxidants did not diminish and perhaps even enhanced the antiarrhythmic action of amiodarone. Thus, co-administration of antioxidants with amiodarone may lead to the more widespread application of amiodarone, which is currently the most potent available antiarrhythmic agent, but its clinical use is limited due the potentially severe toxic effect In hypertensive patients with normal ejection fraction, the most common precursor condition of heart failure with preserved ejection fraction, the potential primary causal role of oxidative stress and inflammation in the left ventricular systolic, diastolic and atrial dysfunction, which are important determinants of the transition of hypertensive heart disease to heart failure with preserved ejection fraction was verified. Orv. Hetil., 2015, 156(47), 1921–1925.

scholarly journals Primary prevention of chronic anthracycline cardiotoxicity with ACE inhibitor is temporarily effective in rabbits, but benefits wane in post-treatment follow-up

2021 ◽  
Author(s):  
Zuzana Pokorna ◽  
Petra Kollárová-Brázdová ◽  
Olga Lenčová-Popelová ◽  
Eduard Jirkovský ◽  
Jan Kubeš ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Troponin T ◽  
Rabbit Model ◽  
Left Ventricular ◽  
Post Treatment ◽  
Cardiac Damage ◽  
Anthracycline Cardiotoxicity ◽  
Related Mortality

Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent anthracycline-induced cardiac damage and provide long-lasting cardioprotection. This study aimed to examine the cardioprotective effects of perindopril on chronic anthracycline cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic daunorubicin treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of daunorubicin-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented heart failure-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for dexrazoxane in the same model. Hence, in this study, perindopril provided only temporary control of anthracycline cardiotoxicity development, which may be associated with the lack of effects on anthracycline-induced and topoisomerase II beta-dependent DNA damage responses in the heart.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

The Pattern of Ventricular Remodeling Influences the Level of Oxidative Stress in Heart Failure Patients

2017 ◽  
Vol 68 (7) ◽  
pp. 1506-1511
Author(s):  
Cerasela Mihaela Goidescu ◽  
Anca Daniela Farcas ◽  
Florin Petru Anton ◽  
Luminita Animarie Vida Simiti
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Clinical Laboratory ◽  
Left Ventricular ◽  
Control Group ◽  
Reactive Protein ◽  
Lv Mass ◽  
Few Data

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.

Sign in / Sign up

Export Citation Format

Share Document