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Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment.

Guo Q, Guo J, Yang R, Peng H, Zhao J, Li L, Peng S - Oxid Med Cell Longev (2015)

Bottom Line: Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations.CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG).Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number.

View Article: PubMed Central - PubMed

Affiliation: Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China ; Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.

ABSTRACT
The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.

No MeSH data available.


Related in: MedlinePlus

Light micrograph demonstrating the effect of CVB-D on DOX-induced myocardial histological alterations. Representative photomicrographs of mouse heart stained with H&E. (a) Normal saline-treated control; (b) CVB-D pretreated group; (c) DOX-treated group; (d) CVB-D plus DOX-treated group. Arrows indicate areas of histological changes including reduced myofibrils, swelling, vacuolization, and nuclear condensation or dissolution. Scale bar = 20 μm.
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fig2: Light micrograph demonstrating the effect of CVB-D on DOX-induced myocardial histological alterations. Representative photomicrographs of mouse heart stained with H&E. (a) Normal saline-treated control; (b) CVB-D pretreated group; (c) DOX-treated group; (d) CVB-D plus DOX-treated group. Arrows indicate areas of histological changes including reduced myofibrils, swelling, vacuolization, and nuclear condensation or dissolution. Scale bar = 20 μm.

Mentions: To demonstrate cardiac morphological alterations, sections of mouse heart tissue stained with hematoxylin-eosin were examined by light microscopy. As shown in Figure 2, heart section from control showed normal cardiac morphology. DOX induced obvious myocardial pathology including reduced myofibrils, swelling, vacuolization, and nuclear condensation or dissolution. CVB-D by itself had no effect on cardiac morphology; however, pretreatment with CVB-D significantly ameliorated DOX-induced lesions on myocardial morphology. DOX-induced cardiotoxicity has been shown to manifest similar pathophysiological characteristics with myocardial infarction-induced cardiac injury, such as heart dysfunction and morphology alterations. Thus, these findings are consistent with the recent studies which indicate that CVB-D provides efficient protection against myocardial infarction-induced cardiac dysfunction and pathological changes.


Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment.

Guo Q, Guo J, Yang R, Peng H, Zhao J, Li L, Peng S - Oxid Med Cell Longev (2015)

Light micrograph demonstrating the effect of CVB-D on DOX-induced myocardial histological alterations. Representative photomicrographs of mouse heart stained with H&E. (a) Normal saline-treated control; (b) CVB-D pretreated group; (c) DOX-treated group; (d) CVB-D plus DOX-treated group. Arrows indicate areas of histological changes including reduced myofibrils, swelling, vacuolization, and nuclear condensation or dissolution. Scale bar = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4446494&req=5

fig2: Light micrograph demonstrating the effect of CVB-D on DOX-induced myocardial histological alterations. Representative photomicrographs of mouse heart stained with H&E. (a) Normal saline-treated control; (b) CVB-D pretreated group; (c) DOX-treated group; (d) CVB-D plus DOX-treated group. Arrows indicate areas of histological changes including reduced myofibrils, swelling, vacuolization, and nuclear condensation or dissolution. Scale bar = 20 μm.
Mentions: To demonstrate cardiac morphological alterations, sections of mouse heart tissue stained with hematoxylin-eosin were examined by light microscopy. As shown in Figure 2, heart section from control showed normal cardiac morphology. DOX induced obvious myocardial pathology including reduced myofibrils, swelling, vacuolization, and nuclear condensation or dissolution. CVB-D by itself had no effect on cardiac morphology; however, pretreatment with CVB-D significantly ameliorated DOX-induced lesions on myocardial morphology. DOX-induced cardiotoxicity has been shown to manifest similar pathophysiological characteristics with myocardial infarction-induced cardiac injury, such as heart dysfunction and morphology alterations. Thus, these findings are consistent with the recent studies which indicate that CVB-D provides efficient protection against myocardial infarction-induced cardiac dysfunction and pathological changes.

Bottom Line: Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations.CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG).Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number.

View Article: PubMed Central - PubMed

Affiliation: Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China ; Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.

ABSTRACT
The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.

No MeSH data available.


Related in: MedlinePlus