Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products

Yu, Jie; Wang, Changxi; Kong, Qi; Wu, Xing; Lu, Jin‐Jian; Chen, Xiuping

doi:10.1016/j.phymed.2018.01.009

Cited by 114 publications

(82 citation statements)

References 162 publications

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“…Cardiotoxicity is the major and the most serious adverse effect of DOX which limit its clinical usefulness. Many strategies have been tried to minimize this serious side effects by using combination treatment with cardioprotective agent and synthesis of DOX liposomes [7,8,9,10,26,27,28]. Among the possible potential chemosensitizer is ATX which has cytotoxic activity chemoprotective effect against chemothe adverse effects [12,29,32].…”

Section: Photomicrograph Of Myocardium Section Of a Rat After 48 Hrsmentioning

confidence: 99%

“…It is well known that the heart tissues are highly susceptible to oxidative stress due to its inherent decreased detoxifying natural antioxidants [8,11].…”

Section: Photomicrograph Of Myocardium Section Of a Rat After 48 Hrsmentioning

confidence: 99%

“…Also, it has been reported that this toxicity is mediated through cardiac tissues inflammation [7]. Between the importance of DOX in cancer treatment and the increase of the incidence of its induced cardiotoxicity, it has become increasingly important to find pharmacological remedies with protective effects against this serious side effect [7,8]. Variety of approaches have been Investigated as the addition of natural compound with chemopreventive or anticancer properties to the DOX treatment protocol [9,10,11].…”

Section: Introductionmentioning

confidence: 99%

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Cardioprotective Effect of Marine Astaxanthin on Doxorubicin-Induced Cardiotoxicity in Normal Rats

AlQahtani

Osman

Damanhouri

et al. 2019

JPRI

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Background: Doxorubicin (DOX) is an effective antineoplastic drug indicated to treat many cancerous diseases but its clinical usefulness is limited by many side effects. The main and the most serious one is DOX induced cardiotoxicity. Many strategies have been tried to minimize this side effect such as addition of cardioprotective agent to DOX treatment protocols. Aims: The aim of this work was directed to investigate whether marine astaxanthin (ATX), a xanthophyll carotenoid pigment with potent antioxidant effect, could protect heart against the cardiotoxicity induced by DOX. Methodology: Forty Male Wister rats were divided into four equal groups and treated for one week as follow: Group I rats were treated with normal saline (2 ml/kg, x7, i.p.) and considered a control group. Group II rats were treated with ATX (40 mg/kg, x7, i.p.). Group III rats were treated with AlQahtani et al.; JPRI, 27(3): 1-11, 2019; Article no.JPRI.48804 2 normal saline (2 ml/kg, x7, i.p.) and a single dose of DOX (20 mg/kg, i.p.) at day 7. Finally, group IV rats were treated with ATX (40 mg/kg, x7, i.p) and with a single dose of DOX (20 mg/kg, i.p.) at day 7. After 24 and 48 hrs of treatment, rats were anesthetized and prepared for collection of blood samples and heart isolation. The cardioprotective effect of ATX against DOX induced cardiotoxicity were evaluated by measurement of the serum level of cardiac enzymes CPK by colorimetric assay and CK-MB by Eliza. Also the levels of serum total antioxidant capacity (TAC) were measured colorimetrically. In addition, the Malondialdehyde (MDA), reduced glutathione, glutathione peroxidase (GPx) levels and superoxide dismutase (SOD) were determined in heart tissues homogenate by colorimetric method. In addition, Heart sample were taken for histopathology studies. Results: The Addition of ATX to DOX significantly (p<0.05) decreased the serum level of cardiac enzymes (CPK, CK-MB) and increased the serum total antioxidant capacity in compare with these levels in sera of rats treated with DOX only. This addition also significantly decreased the level of malondialdehyde and increased the reduced glutathione and glutathione peroxidase and superoxide dismutase significantly in the heart tissues homogenate in compare to corresponding levels in rats treated with DOX alone. Histopathological investigation of cardiac tissues confirmed the biochemical studies, where addition of ATX to DOX treatment protocol showed that the fragmentation of the muscle fiber revealed normal with central vesicular nuclei and prevented a marked disruption of normal cardiac architecture which resulted from DOX treatment. Conclusion: Marine astaxanthin provides excellent cardioprotective effect against doxorubicin induced cardiotoxicity in rats. Original Research Article

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Section: Photomicrograph Of Myocardium Section Of a Rat After 48 Hrsmentioning

confidence: 99%

“…It is well known that the heart tissues are highly susceptible to oxidative stress due to its inherent decreased detoxifying natural antioxidants [8,11].…”

Section: Photomicrograph Of Myocardium Section Of a Rat After 48 Hrsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cardioprotective Effect of Marine Astaxanthin on Doxorubicin-Induced Cardiotoxicity in Normal Rats

AlQahtani

Osman

Damanhouri

et al. 2019

JPRI

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“…Anticancer compounds, particularly anthracyclines among them, often exhibit cardiotoxicity, which restricts the application of that type of antineoplastic agent. Although it has been studied widely, the mechanism has not been clearly determined (Yu et al, 2018).…”

Section: Decomposition Of Topoisomerase-inhibitor Effectmentioning

confidence: 99%

Orthogonal linear separation analysis: an approach to decompose the complex effects of a perturbagen

Mizuno

Kinoshita

Maedera

et al. 2018

Preprint

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Drugs have multiple, not single, effects. Decomposition of drug effects into basic components helps us to understand the pharmacological properties of a drug and contributes to drug discovery. We have extended factor analysis and developed a novel profile data analysis method, orthogonal linear separation analysis (OLSA). OLSA contracted 11,911 genes to 118 factors from transcriptome data of MCF7 cells treated with 318 compounds in Connectivity Map. Ontology of the main genes constituting the factors detected significant enrichment of the ontology in 65 of 118 factors and similar results were obtained in two other data sets. One factor discriminated two Hsp90 inhibitors, geldanamycin and radicicol, while clustering analysis could not. Doxorubicin was estimated to inhibit Na+/K+ATPase, one of the suggested mechanisms of doxorubicin-induced cardiotoxicity. Based on the factor including PI3K/AKT/mTORC1 inhibition activity, 5 compounds were predicted to be novel autophagy inducers, and other analysis including western blotting revealed that 4 of the 5 actually induced autophagy. These findings indicate the potential of OLSA to decompose the effects of a drug and identify its basic components. (<175 words)

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“…DOX is a widely prescribed drug for the management of solid tumours including ovary, breast and gastrointestinal cancers and haematologic malignancies. 1 One important limiting factor in the prescription of DOX is its dose-dependent cardiotoxicity that is likely to develop into congestive heart failure (CHF) when cumulative dose exceeds 300 mg/m 22 | 365 NAZARI SOLTAN AHMAD eT AL.…”

Section: Introductionmentioning

confidence: 99%

β‐LAPachone ameliorates doxorubicin‐induced cardiotoxicity via regulating autophagy and Nrf2 signalling pathways in mice

Ahmad

Sanajou

Kalantary‐Charvadeh

et al. 2019

Basic Clin Pharma Tox

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β‐LAPachone (B‐LAP) is a naphthoquinone that possesses antioxidant properties. In the present investigation, the protective effect of B‐LAP against doxorubicin (DOX)‐induced cardiotoxicity was examined in mice. Thirty‐five mice were divided into 5 groups: control group, B‐LAP (5 mg/kg) group, DOX (15 mg/kg) group, DOX+B‐LAP (2.5 mg/kg) group and DOX+B‐LAP (5 mg/kg) group. B‐LAP was administered orally for 14 days of experimental period. A single dose of DOX (15 mg/kg) was injected intraperitoneally on day 3. Cardiac function, histoarchitecture, indices of oxidative stress and circulating markers of cardiac injury were examined. B‐LAP (5 mg/kg) decreased serum levels of lactate dehydrogenase (LDH), creatine kinase MB (CK‐MB) and cardiac troponin I (cTnI), and ameliorated cardiac histopathological alterations. In addition to increasing cellular NAD+/NADH ratio, B‐LAP up‐regulated the cardiac levels of SIRT1, beclin‐1, p‐LKB1 and p‐AMPK, and reduced the cardiac levels of p‐mTOR, interleukin (IL)‐1β, TNF (tumour necrosis factor)‐α and caspase‐3. B‐LAP also elevated the nuclear accumulation of Nrf2 and simultaneously up‐regulated the protein levels of haem oxygenase (HO‐1) and glutathione S‐transferase (GST) in the hearts of DOX mice. While B‐LAP reduced malondialdehyde concentrations in heart of DOX‐treated mice, it further promoted the activities of cardiac superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT).In accordance with increased cell survival, B‐LAP significantly improved the cardiac function of DOX mice. Collectively, these findings underline the protective potential of B‐LAP against DOX‐induced cardiotoxicity by regulating autophagy and AMPK/Nrf2 signalling pathway in mice.

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Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products

Cited by 114 publications

References 162 publications

Cardioprotective Effect of Marine Astaxanthin on Doxorubicin-Induced Cardiotoxicity in Normal Rats

Cardioprotective Effect of Marine Astaxanthin on Doxorubicin-Induced Cardiotoxicity in Normal Rats

Orthogonal linear separation analysis: an approach to decompose the complex effects of a perturbagen

β‐LAPachone ameliorates doxorubicin‐induced cardiotoxicity via regulating autophagy and Nrf2 signalling pathways in mice

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