Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats

Zhang, Haiyan; Lü, Xiang; Liu, Zhengxia; Du, Kang

doi:10.3892/ijmm.2018.3928

Cited by 8 publications

(8 citation statements)

References 51 publications

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“…In response to stressed conditions, there is phosphorylation of IκB by IKK which causes nuclear translocation of in ammatory cytokines, i.e., TNF and IL-6. HMGB1 has also been shown to increase the production of in ammatory cytokines by interacting with RAGE and toll-like receptors(Zhang et al 2018). In this study, there was an increased level of MAPK, NF-κB/IKKβ, HMGBI, and in ammatory cytokines in the DC and D+I group rats, which were signi cantly reduced by Morin treatment.…”

supporting

confidence: 54%

Modulation of MAPK/Nrf2-HO1/Akt-eNOS/inflammasome pathways by morin in myocardial infarction in diabetic rats

Verma

Malik

Sahu

et al. 2023

Preprint

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Purpose: Diabetes is a risk factor that predisposes to atherosclerotic cardiovascular diseases. The risk of myocardial infarction in diabetes is 3-4 times higher. In diabetes, high blood glucose levels lead to vascular inflammation which accelerates atherosclerosis. Hence, we evaluate the mechanism involved in the cardioprotective action of Morin in diabetic rats. Methods: In male Wistar rats, streptozotocin (70 mg/kg; i.p.) was administered to induce diabetes and, rats with fasting blood glucose levels >400 mg/dl were considered diabetic and included in the study. These rats were divided into five groups (n=8), i.e., Normal; Diabetic-control; Diabetes+Isoproterenol (ISO); Diabetes+ISO+Morin and, Diabetes+Morin. Morin was orally administered at the dose of 40 mg/kg for 28 days and on the 27th and 28th day ISO was administered to designate groups at the dose of 85mg/kg s.c., to induce myocardial infarction. Results: Free radical generation in diabetes as well as the rush of ROS following ISO administration leads to activation of the intrinsic as well as extrinsic pathways of apoptosis. Morin significantly (p≤0.05) reduced oxidative stress (áGSH, âMDA, áSOD), cardiac injury markers (âCK-MB, âLDH), inflammation (âTNF, âIL-6) and apoptosis (âBax, áBCl2, áCaspase-3). In addition, it also reduced serum insulin and blood glucose levels. Histopathology showed cardio-protection with morin. Akt/eNOS, Nrf2/HO-1, MAPK signalling pathways and Insulin signal transduction pathways were positively modulated by Morin pre-treatment. It also significantly modulated NLRP3 inflammasome formation. Conclusion: Morin attenuated oxidative stress and inflammation and also modified expression of various molecular pathways to mitigate cardiomyocyte damage during ISO induced MI in diabetic rats.

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supporting

confidence: 54%

Modulation of MAPK/Nrf2-HO1/Akt-eNOS/inflammasome pathways by morin in myocardial infarction in diabetic rats

Verma

Malik

Sahu

et al. 2023

Preprint

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“…In a rat model of DOX cardiotoxicity, rosuvastatin co-administration showed beneficial effects on cardiac LV function and myocardial injury 4 weeks after treatment cessation [114]. Rosuvastatin moreover reduced DOX-induced pro-inflammatory effects in rats [115]. Atorvastatin in turn ameliorated oxidative stress and DNA and cellular damage in a mouse model of DOX cardiotoxicity [116].…”

Section: Statinsmentioning

confidence: 99%

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

Timm

Tyler

2020

Cardiovasc Drugs Ther

121

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Doxorubicin is a commonly used chemotherapeutic agent for the treatment of a range of cancers, but despite its success in improving cancer survival rates, doxorubicin is cardiotoxic and can lead to congestive heart failure. Therapeutic options for this patient group are limited to standard heart failure medications with the only drug specific for doxorubicin cardiotoxicity to reach FDA approval being dexrazoxane, an iron-chelating agent targeting oxidative stress. However, dexrazoxane has failed to live up to its expectations from preclinical studies while also bringing up concerns about its safety. Despite decades of research, the molecular mechanisms of doxorubicin cardiotoxicity are still poorly understood and oxidative stress is no longer considered to be the sole evil. Mitochondrial impairment, increased apoptosis, dysregulated autophagy and increased fibrosis have also been shown to be crucial players in doxorubicin cardiotoxicity. These cellular processes are all linked by one highly conserved intracellular kinase: adenosine monophosphate-activated protein kinase (AMPK). AMPK regulates mitochondrial biogenesis via PGC1α signalling, increases oxidative mitochondrial metabolism, decreases apoptosis through inhibition of mTOR signalling, increases autophagy through ULK1 and decreases fibrosis through inhibition of TGFβ signalling. AMPK therefore sits at the control point of many mechanisms shown to be involved in doxorubicin cardiotoxicity and cardiac AMPK signalling itself has been shown to be impaired by doxorubicin. In this review, we introduce different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and we discuss the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity.

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“…Statins are extensively used for treatment of cardiovascular diseases due to their cholesterol-lowering effects, but they also exert beneficial anti-inflammatory functions. These effects are partly brought about by inhibition of both the HMGB1/TLR4-and HMGB1/ RAGE-mediated pathways (Liu et al 2013;Wu et al 2013;Han et al 2015;Zhu and Fang 2016;Zhang et al 2018a) (Fig. 2).…”

Section: Statinsmentioning

confidence: 99%

Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?

Andersson

Ottestad

Tracey

2020

Mol Med

199

212

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Background: The 2019 novel coronavirus disease (COVID-19) causes for unresolved reasons acute respiratory distress syndrome in vulnerable individuals. There is a need to identify key pathogenic molecules in COVID-19-associated inflammation attainable to target with existing therapeutic compounds. The endogenous damage-associated molecular pattern (DAMP) molecule HMGB1 initiates inflammation via two separate pathways. Disulfide-HMGB1 triggers TLR4 receptors generating pro-inflammatory cytokine release. Extracellular HMGB1, released from dying cells or secreted by activated innate immunity cells, forms complexes with extracellular DNA, RNA and other DAMP or pathogen-associated molecular (DAMP) molecules released after lytic cell death. These complexes are endocytosed via RAGE, constitutively expressed at high levels in the lungs only, and transported to the endolysosomal system, which is disrupted by HMGB1 at high concentrations. Danger molecules thus get access to cytosolic proinflammatory receptors instigating inflammasome activation. It is conceivable that extracellular SARS-CoV-2 RNA may reach the cellular cytosol via HMGB1-assisted transfer combined with lysosome leakage. Extracellular HMGB1 generally exists in vivo bound to other molecules, including PAMPs and DAMPs. It is plausible that these complexes are specifically removed in the lungs revealed by a 40% reduction of HMGB1 plasma levels in arterial versus venous blood. Abundant pulmonary RAGE expression enables endocytosis of danger molecules to be destroyed in the lysosomes at physiological HMGB1 levels, but causing detrimental inflammasome activation at high levels. Stress induces apoptosis in pulmonary endothelial cells from females but necrosis in cells from males.Conclusion: Based on these observations we propose extracellular HMGB1 to be considered as a therapeutic target for COVID-19.

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Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats

Cited by 8 publications

References 51 publications

Modulation of MAPK/Nrf2-HO1/Akt-eNOS/inflammasome pathways by morin in myocardial infarction in diabetic rats

Modulation of MAPK/Nrf2-HO1/Akt-eNOS/inflammasome pathways by morin in myocardial infarction in diabetic rats

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?

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