An in vivo and in vitro model on the protective effect of corilagin on doxorubicin-induced cardiotoxicity via regulation of apoptosis and PI3-K/AKT signaling pathways.

Abstract

Globally, doxorubicin (DOX)-induced cardio dysfunction is a serious cause of morbidity and mortality in cancerous patients. An adverse event of cardiotoxicity is the main deem to restrict in the clinical application by oncologists. Corilagin (CN) is well known for its antioxidative, anti-fibrosis, and anticancer effects. Herein, we aimed to evaluate the action of CN on DOX-induced experimental animals and H9c2 cells. The myocardium-specific marker, CK-MB, and the influx of mitochondrial calcium levels were measured by using commercial kits. Biochemical indices reflecting oxidative stress and antioxidant attributes such as malondialdehyde, glutathione peroxidase, reduced glutathione, superoxide dismutase, and catalase were also analyzed in DOX-induced cardiotoxic animals. In addition, mitochondrial ROS were measured by DCFH-DA in H9c2 cells under fluorescence microscopy. DOX induction significantly increased oxidative stress levels and also modulated apoptosis/survival protein expressions in myocardial tissues. Western blots were used to measure the expressional levels of Bax/Bcl-2, caspase-3, PI3-K/AKT, and PPARγ signaling pathways. Histological studies were executed to observe morphological changes in myocardial tissues. All of these DOX-induced effects were attenuated by CN (100 mg/kg bw). These in vitro and in vivo results point towards the fact that CN might be a novel cardioprotective agent against DOX-induced cardiotoxicity through modulating cardio apoptosis and oxidative stress.

• Authors: Lianqin Ding, Di Li, Ming Li, Dexia Zhao, Annamalai Govindhan, Mani Santhoshkumar, Hongli Xiang
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 35 Issue 12 Pg. e22926 (Dec 2021) ISSN: 1099-0461 [Electronic] United States
• PMID: 34605098 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Antibiotics, Antineoplastic
• Biomarkers
• Glucosides
• Hydrolyzable Tannins
• Reactive Oxygen Species
• corilagin
• Doxorubicin
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Antibiotics, Antineoplastic (toxicity)
• Apoptosis (drug effects)
• Biomarkers (metabolism)
• Cell Line
• Doxorubicin (toxicity)
• Glucosides (pharmacology)
• Heart (drug effects)
• Humans
• Hydrolyzable Tannins (pharmacology)
• In Vitro Techniques
• Mitochondria, Heart (drug effects, enzymology, metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)