Effects of Ganoderma lucidum polysaccharides against doxorubicin-induced cardiotoxicity
| Autor: | Fan Xu, Sheng-lin Zhang, Ping-ping Lin, Xu Xiao, Qing-shan Li, Lan-fang Liu, Li Zhang, Xiao Li |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Reishi Anthracycline NF-E2-Related Factor 2 Apoptosis macromolecular substances Pharmacology medicine.disease_cause Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Polysaccharides In vivo Lactate dehydrogenase polycyclic compounds medicine Animals Myocytes Cardiac Doxorubicin RNA Messenger Cardiotoxicity L-Lactate Dehydrogenase biology Protein Stability business.industry organic chemicals technology industry and agriculture General Medicine Cullin Proteins Mitochondria carbohydrates (lipids) Oxidative Stress 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Cytokines Creatine kinase Inflammation Mediators business Oxidative stress medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 95:504-512 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2017.08.118 |
| Popis: | Doxorubicin (DOX) is a widely used anthracycline derivative anticancer drug, but the use of DOX in clinical applications is limited by its cardiotoxicity. In the current research, we were aiming to assess the effects of Ganoderma lucidum polysaccharides (GLPS) on DOX-induced cardiotoxicity and to illustrate the associated mechanisms. H9c2 rat cardiomyocytes were treated with DOX in the absence or presence of GLPS, and we found GLPS treatment ameliorated DOX-induced H9c2 cell death. Moreover, results of in vivo studies indicated that GLPS significantly decreased the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) and attenuated DOX-induced histological changes of the heart tissues. In addition, we found DOX administration promoted myocardial apoptosis, potentiated oxidative stress, decreased the activities of antioxidant enzymes and increased the production of pro-inflammatory cytokines. However, GLPS pretreatment markedly attenuated all these untoward effects of DOX. Furthermore, GLPS pretreatment was found to inhibit Cul3-mediated K48-linked polyubiquitination of Nrf2 through suppressing Cul3 expression, thereby stabilizing Nrf2 expression in H9c2 cells after DOX treatment, leading to the decreased expression of P53 and p-P65 and increased levels of MDM2 and HO-1, resulted in the attenuated apoptosis, oxidative stress and inflammation induced by DOX. |
| Databáze: | OpenAIRE |
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