Beneficial effects of carbon monoxide-releasing molecule-2 (CORM-2) on acute doxorubicin cardiotoxicity in mice: Role of oxidative stress and apoptosis

Soni, Hitesh; Pandya, Gaurav; Patel, Praful; Acharya, Aviseka; Jain, Mukul; Mehta, Abhishek

doi:10.1016/j.taap.2011.03.013

Cited by 64 publications

(52 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, to draw firm mechanistic conclusions it will be necessary to use a genetic manipulation approach. In addition, although the induction of mitochondrial biogenesis through the administration of CO, CO-releasing molecules, or metformin treatment seemed to be helpful in acute and subacute anthracycline cardiotoxicity settings (Piantadosi and Suliman, 2006;Asensio-López et al, 2011;Soni et al, 2011;Ashour et al, 2012), it will be important to reveal whether this intervention may have a therapeutic value against chronic anthracycline cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Chronic Anthracycline Cardiotoxicity: Molecular and Functional Analysis with Focus on Nuclear Factor Erythroid 2-Related Factor 2 and Mitochondrial Biogenesis Pathways

Jirkovský

Popelová

Kriváková-Stanková

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Anthracycline anticancer drugs (e.g., doxorubicin or daunorubicin) can induce chronic cardiotoxicity and heart failure (HF), both of which are believed to be based on oxidative injury and mitochondrial damage. In this study, molecular and functional changes induced by chronic anthracycline treatment with progression into HF in post-treatment follow-up were analyzed with special emphasis on nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC1␣) pathways. Chronic cardiotoxicity was induced in rabbits with daunorubicin (3 mg/kg, weekly for 10 weeks), and the animals were followed for another 10 weeks. Echocardiography revealed a significant drop in left ventricular (LV) systolic function during the treatment with marked progression to LV dilation and congestive HF in the follow-up. Although daunorubicin-induced LV lipoperoxidation was found, it was only loosely associated with cardiac performance. Furthermore, although LV oxidized glutathione content was increased, the oxidized-to-reduced glutathione ratio itself remained unchanged. Neither Nrf2, the master regulator of antioxidant response, nor the majority of its target genes showed up-regulation in the study. However, down-regulation of manganese superoxide dismutase and NAD(P)H dehydrogenase [quinone] 1 were observed together with heme oxygenase 1 up-regulation. Although marked perturbations in mitochondrial functions were found, no induction of PGC1␣-controlled mitochondrial biogenesis pathway was revealed. Instead, especially in the post-treatment period, an impaired regulation of this pathway was observed along with down-regulation of the expression of mitochondrial genes. These results imply that global oxidative stress need not be a factor responsible for the development of anthracycline-induced HF, whereas suppression of mitochondrial biogenesis might be involved.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic Anthracycline Cardiotoxicity: Molecular and Functional Analysis with Focus on Nuclear Factor Erythroid 2-Related Factor 2 and Mitochondrial Biogenesis Pathways

Jirkovský

Popelová

Kriváková-Stanková

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…CORM-2 dosing was based on past dose titration studies and reported effectiveness of a single systemic 8-mg/kg dose in rodents (44)(45)(46). CORM-2 (8 mg/kg i.v.…”

Section: Methodsmentioning

confidence: 99%

Carbon monoxide–based therapy ameliorates acute pancreatitis via TLR4 inhibition

Xue¹,

Habtezion²

2013

J. Clin. Invest.

View full text Add to dashboard Cite

The protective role of hemeoxygenase-1 (HO-1) in various inflammatory conditions is mediated in part by its products, carbon monoxide (CO) and biliverdin. Here we investigated a therapeutic role for CO and COprimed cells in acute pancreatitis (AP). In a mouse model of AP, treatment with CO-releasing molecule-2 (CORM-2) decreased mortality, pancreatic damage, and lung injury. CORM-2 decreased systemic inflammatory cytokines, suppressed systemic and pancreatic macrophage TNF-α secretion, and inhibited macrophage TLR4 receptor complex expression. In both human and mouse cells, CORM-2 inhibited endogenous and exogenous ligand-dependent TLR4 activation, which indicates that CORM-2 could be therapeutic for both early and late stages of AP, which involve sterile-and endotoxin-mediated inflammation, respectively. Mice engrafted with TLR4-deficient hematopoietic cells were protected against caerulein-induced AP. In the absence of leukocyte TLR4 expression, CORM-2 did not confer additional protection, which indicates that CORM-2-dependent effects are mediated via suppression of macrophage TLR4 activation. We determined that CO was directly responsible for the protective effects of CORM-2 in AP, as inactive forms of CORM-2 were ineffective. Importantly, adoptive transfer of CORM-2-primed cells reduced AP. Such a therapeutic approach would translate the beneficial effects of CO-based therapies, avoiding CO-or CO-RM-mediated toxicities in AP and a wide range of diseases.

show abstract

“…Doxorubicin is a chemotherapeutic drug widely used in many combined regimens for NHL. However, fatal cardiotoxicity has been a major limitation (Soni et al, 2011). Strategies to decrease doxorubicin toxicity by minimizing doxorubicin effects in chemotherapeutic doses and improving its efficacy are urgently needed to better treat cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells

Dangkong

Limpanasithikul

2014

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Doxorubicin is a chemotherapy agent used in non-Hodgkin's lymphoma but side effects limit its use. Citral is a mixture of neral and geranial found in essential oils of lemon grass. Objectives: We evaluated the activity of citral, doxorubicin, and combination on cytotoxicity, apoptosis, and anti-proliferative effects using human lymphoma Ramos cells. Materials and methods: Cells were treated with doxorubicin alone or in combination with citral (10, 20, and 40 mM). Cytotoxic and apoptosis studies were done after 24 and 18 h incubations, respectively. Cytotoxic effects of citral on normal human peripheral blood mononuclear cells (PBMCs) were also investigated for its safety. Changes in the expression of BCL-2 family genes were analyzed by quantitative RT-PCR. Results: Citral had cytotoxicity on cells with an IC 50 value of 77.19 ± 4.95 mM. Citral at concentrations of 10, 20, and 40 mM additively increased the cytotoxic and apoptotic effects of doxorubicin, leading to decreased IC 50 (mM) of the drug from 2.50 ± 0.01 to 2.16 ± 0.03, 1.90 ± 0.04, and 1.23 ± 0.04, respectively. Enhanced cytotoxicity was not observed in normal human PBMCs. Citral (40 mM) in combination with doxorubicin (1.5 mM) increased the expression of pro-apoptotic protein BAK but significantly decreased the expression of antiapoptotic protein BCL-XL to 5.26-fold compared with doxorubicin-treated cells. It did not change the anti-proliferative activity of drug. Discussion and conclusion: Citral potentiated cytotoxicity of doxorubicin by increasing apoptotic effects. We conclude that citral may have beneficial effects in patients with B cell lymphoma treated with chemotherapy.

show abstract

Beneficial effects of carbon monoxide-releasing molecule-2 (CORM-2) on acute doxorubicin cardiotoxicity in mice: Role of oxidative stress and apoptosis

Cited by 64 publications

References 51 publications

Chronic Anthracycline Cardiotoxicity: Molecular and Functional Analysis with Focus on Nuclear Factor Erythroid 2-Related Factor 2 and Mitochondrial Biogenesis Pathways

Chronic Anthracycline Cardiotoxicity: Molecular and Functional Analysis with Focus on Nuclear Factor Erythroid 2-Related Factor 2 and Mitochondrial Biogenesis Pathways

Carbon monoxide–based therapy ameliorates acute pancreatitis via TLR4 inhibition

Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells

Contact Info

Product

Resources

About