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Chitosan oligosaccharides prevent doxorubicin-induced oxidative stress and cardiac apoptosis through activating p38 and JNK MAPK mediated Nrf2/ARE pathway
- Source :
- Chemico-biological interactions. 305
- Publication Year :
- 2019
-
Abstract
- Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs; however, the incidence of cardiotoxicity compromises its therapeutic index. Oxidative stress and apoptosis are believed to be involved in DOX-induced cardiotoxicity. Chitosan oligosaccharides (COS), the enzymatic hydrolysates of chitosan, have been reported to possess diverse biological activities including antioxidant and anti-apoptotic properties. The objective of the present study was to investigate the potential role of COS against DOX-induced cardiotoxicity, and the effects of COS on apoptosis and oxidative stress in rats and H9C2 cells. Furthermore, we also shed light on the involved pathways during the whole process. For this purpose, first, we demonstrated that COS exhibited a significant protective effect on cardiac tissue by not only inducing a decrease in body and heart growth but also ameliorated oxidative damage and ECG alterations in DOX-treated rats. Second, we found that COS reversed the decrease of cell viability induced by DOX, reduced the intracellular reactive oxygen species (ROS), increased the mitochondrial membrane potential (MMP) and Bcl-2/Bax ratio. COS treatment also results in reduced caspase-3 and caspase-9 expressions, and an increase in the phosphorylation of MAPKs (mitogen-activated protein kinases) in DOX-exposed H9C2 cells. Additionally, cellular homeostasis was re-established via stabilization of MAPK mediated nuclear factor erythroid 2-related factor 2/antioxidant-response element (Nrf2/ARE) signaling and transcription of downstream cytoprotective genes. In summary, these findings suggest that COS could be a potential candidate for the prevention and treatment of DOX-induced cardiotoxicity.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Male
NF-E2-Related Factor 2
Heart growth
p38 mitogen-activated protein kinases
Cellular homeostasis
Apoptosis
Toxicology
medicine.disease_cause
p38 Mitogen-Activated Protein Kinases
Cell Line
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Myocytes, Cardiac
Creatine Kinase
Membrane Potential, Mitochondrial
Cardiotoxicity
Chitosan
Chemistry
Kinase
JNK Mitogen-Activated Protein Kinases
Heart
General Medicine
Antioxidant Response Elements
Cell biology
Rats
Oxidative Stress
030104 developmental biology
Proto-Oncogene Proteins c-bcl-2
Doxorubicin
030220 oncology & carcinogenesis
Reactive Oxygen Species
Oxidative stress
Signal Transduction
Subjects
Details
- ISSN :
- 18727786
- Volume :
- 305
- Database :
- OpenAIRE
- Journal :
- Chemico-biological interactions
- Accession number :
- edsair.doi.dedup.....512176fdc95e5449ecc5247c7082fc79