Protective effect of calpain inhibitor N-acetyl-l-leucyl-l-leucyl-l-norleucinal on acute alcohol consumption related cardiomyopathy

Kartkaya, Kazım; Kanbak, Güngör; Oğlakçı, Ayşegül; Burukoğlu, Dilek; Özer, Mehmet Caner

doi:10.1007/s11033-014-3560-4

Cited by 10 publications

(5 citation statements)

References 59 publications

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“…The use of Annexin V staining with fluorescence-activated cell sorting has confirmed an alcohol-mediated increase in apoptosis in cardiomyocytes (94, 95). Similarly, the number of apoptotic nuclei detected via TUNEL was increased after acute alcohol in male mice (3 day, 3 g/kg alcohol/day) (20) and male rats (8 g/kg alcohol) (96), as well as in H9c2 cardiomyocytes (100–400 mg/dL, 24 hr), neonatal rat cardiac myocytes (200 mM, 4 hr) and primary cardiomyocytes from adult rats (0.3–0.5% alcohol in media, 4 days). This effect appears specific to cardiomyocytes as there was no detectable increase in apoptosis in alcohol-treated cardiac fibroblasts (97).…”

Section: Apoptosismentioning

confidence: 99%

“…Under in vitro conditions, pro-caspase 3/active caspase 3 protein expression was increased in endothelial progenitor cells (25 mM, 48 hr) (100), while cleaved caspase 3 was increased in H9c2 cells (100–400 mM, 24 hr) and neonatal rat cardiac myocytes (200 mM, 4 hr) (89, 95). In contrast, caspase 3 activity was unchanged in rat hearts in response to acute alcohol intoxication, despite increased caspase 3 staining in isolated cardiomyocytes (96). Therefore, the majority of recent data indicate that caspase 3 is increased in response to acute and chronic alcohol indicating apoptotic pathway activation.…”

Section: Apoptosismentioning

confidence: 99%

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Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

Steiner

Lang

2017

The International Journal of Biochemistry & Cell Biology

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Putative mechanisms leading to the development of alcoholic cardiomyopathy (ACM) include the interrelated cellular processes of mitochondria metabolism, oxidative stress and apoptosis. As mitochondria fuel the constant energy demands of this continually contracting tissue, it is not surprising that alcohol-induced molecular changes in this organelle contribute to cardiac dysfunction and ACM. As the causal relationship of these processes with ACM has already been established, the primary objective of this review is to provide an update of the experimental findings to more completely understand the aforementioned mechanisms. Accordingly, recent data indicate that alcohol impairs mitochondria function assessed by membrane potential and respiratory chain activity. Indictors of oxidative stress including superoxide dismutase, glutathione metabolites and malondialdehyde are also adversely affected by alcohol oftentimes in a sex-dependent manner. Additionally, myocardial apoptosis is increased based on assessment of TUNEL staining and caspase activity. Recent work has also emerged linking alcohol-induced oxidative stress with apoptosis providing new insight on the codependence of these interrelated mechanisms in ACM. Attention is also given to methodological differences including the dose of alcohol, experimental model system and the use of males versus females to highlight inconsistencies and areas that would benefit from establishment of a consistent model.

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Section: Apoptosismentioning

confidence: 99%

Section: Apoptosismentioning

confidence: 99%

Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

Steiner

Lang

2017

The International Journal of Biochemistry & Cell Biology

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“…Calpain-1 belongs to the family of cysteine proteases. Calpain-1 activation has been demonstrated to induce IκBα degradation and NF-κB activation [7]. In a previous study, we found that calpain-1 plays an critical role in atherogenesis through endothelial disorder and inflammation [8].…”

Section: Introductionmentioning

confidence: 99%

Simvastatin Improves Cardiac Hypertrophy in Diabetic Rats by Attenuation of Oxidative Stress and Inflammation Induced by Calpain-1-Mediated Activation of Nuclear Factor-κB (NF-κB)

et al. 2019

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Background Simvastatin, an HMG-CoA reductase inhibitor, has been reported to exert multiple protective effects on the cardiovascular system. However, the molecular mechanism remains to be examined. The present study was designed to study the effects of simvastatin on cardiac hypertrophy in diabetic rats and to explore its potential mechanism. Material/Methods Sprague-Dawley rats were assigned into a control (Con) group, a streptozotocin (STZ) group, and a STZ+simvastatin (STZ+SIM) group. The level of reactive oxygen species (ROS) was measured by using dihydroethidium (DHE) staining. The protein expressions of p65, IκBα, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), calpain-1, and endothelial nitric oxide synthase (eNOS) were examined by Western blot analysis. qPCR was used to detect the levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). Results Simvastatin improved the cardiac hypertrophy of diabetic rats, as demonstrated by decreases in the ratios of left ventricular weight/body weight (LVW/BW) and heart weight/body weight (HW/BW) and by the downregulation of mRNA expression of BNP and ANP in the heart tissue. Simvastatin decreased the protein expressions of VCAM-1, ICAM-1, IL-6, and TNF-α, increased eNOS protein expression, and limited an increase in ROS levels in the heart tissue. Simvastatin increased IκBα protein expression in cytoplasm and inhibited the translocation of p65, the subunit of nuclear factor-κB (NF-κB) to the nucleus from the cytoplasm of the heart tissue. Furthermore, simvastatin attenuated the activity of calpain and calpain-1 protein expression in heart tissue. Conclusions Simvastatin attenuates cardiac hypertrophy in diabetic rats, which might be due to the attenuation of oxidative stress and inflammation induced by calpain-1-mediated activation of NF-κB.

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“…Indeed, it inhibits the cytochrome c oxidase (or complex IV) of the mitochondrial respiratory chain, resulting in a blockage of adenosine-triphosphate synthesis. The suggested mechanism of the cardiac toxicity is an increase in intracellular calcium, due to an increased influx, which activates calpain, a protease responsible for intracellular damages causing cell apoptosis through the caspase pathway 4,5,6 . Despite interesting results of calcium antagonists in vitro no human case of NaN3 poisoning treated with calcium antagonist has been reported yet.…”

mentioning

confidence: 99%

Surviving a Massive Sodium Azide Poisoning with Toxic Cardiomyopathy

Overtchouk¹,

Poissy²,

Thieffry³

et al. 2015

ICFJ

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Sodium azide poisoning is rare (~50 case reports) but can be quickly fatal. A systematic review reported the fatal dose in humans to be over 10 mg/kg 1 . A 69 year-old female was admitted to our hospital for voluntary sodium azide poisoning. She ingested a massive dose of a soup spoon (15 g) of pure sodium azide powder with intention to commit suicide without any co-intoxication. Within minutes, she felt nauseous and had several vomiting. She was immediately brought to the hospital.At admission, 2 hours after the ingestion, despite the absence of hypotension she had widespread marbles on her knees and an extended recoloration time. She had no signs of cardiac insufficiency. Diaphoresis was noticed. Biology showed a balanced metabolic acidosis with (pH of 7.48, bicarbonate 17,2 mmol/L), high blood lactate (6,6 mmol/L) indicating tissue hypoxia, elevated blood glucose (2,1 g/L), normal hypersensitive troponin. The electrocardiogram (ECG) was normal. The patient was immediately treated with gastric lavage and crystalloids. Hyperlactatemia and acidosis resolved within 12 hours.On the 3rd day after the poisoning the biology showed increased hypersensitive troponine (100 ng/mL, normal < 50 ng/ mL). The ECG showed a ST-segment elevation in leads DI, DII, AVL, AVF, and V4 to V6, with reciprocal ST depression in leads AVR and V1 without any chest pain (figure 1). Contemporary blood lactate increased again (4.3 mmol/L), same as liver transaminases (3 times the normal rate) and CRP (80 mg/L). The transthoracic echocardiography showed a decreased left ventricle ejection fraction (LVEF) at 30% with no dilation. Akinesis was noted in the apex, upper third of the lateral and inferior area. The left ventricle was overall hypokinetic. Medium E/E' ratio of 12.5 pointing out elevated left ventricle filling pressure. The right ventricle and the systolic arterial pulmonary pressure were normal. There was no pericardial effusion.She was immediately transferred for emergency coronary angiography which found no clot or coronary spasm, but a 80% stenosis was noticed in the proximal section of the right coronary artery. No angioplasty was carried out. Nitrates were introduced to improve myocardial perfusion.A cardiac MRI (Magnetic Resonance Imaging) was carried out 3 weeks after the poisoning. It showed a LVEF of 52%, a slight overall hypokinesis, no pathological enhancement, thus no myocarditis or infarct sequelae. Besides it showed a circumferential pericardial effusion of moderate volume (maximum 17 millimeters facing the left ventricle).We concluded to toxic cardiomyopathy caused by sodium azide.

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Protective effect of calpain inhibitor N-acetyl-l-leucyl-l-leucyl-l-norleucinal on acute alcohol consumption related cardiomyopathy

Cited by 10 publications

References 59 publications

Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

Simvastatin Improves Cardiac Hypertrophy in Diabetic Rats by Attenuation of Oxidative Stress and Inflammation Induced by Calpain-1-Mediated Activation of Nuclear Factor-κB (NF-κB)

Surviving a Massive Sodium Azide Poisoning with Toxic Cardiomyopathy

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