Sesamol prevents doxorubicin-induced oxidative damage and toxicity on H9c2 cardiomyoblasts

• Published in: Journal of pharmacy and pharmacology Vol. 65; no. 7; pp. 1083 - 1093
• Main Authors: Nayak, Pawan G., Paul, Piya, Bansal, Punit, Kutty, Nampurath Gopalan, Pai, Karkala Sreedhara Ranganath
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-07-2013; Wiley Subscription Services, Inc
• Subjects: Animals; Anti-apoptotic; Antibiotics, Antineoplastic - toxicity; Antioxidants - administration & dosage; Antioxidants - pharmacology; Apoptosis - drug effects; Benzodioxoles - administration & dosage; Benzodioxoles - pharmacology; Cell Line; Cell Survival - drug effects; Cytotoxicity; Dose-Response Relationship, Drug; Doxorubicin; Doxorubicin - toxicity; Free radical; Mutagenicity Tests; Myoblasts, Cardiac - drug effects; Myoblasts, Cardiac - pathology; Oxidative Stress - drug effects; Oxygen; pBR322 DNA; Phenols - administration & dosage; Phenols - pharmacology; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sesamol; Toxicity
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12073

Objectives
Exposure to toxicants like doxorubicin (Dox) damages cellular components by generating reactive oxygen species (ROS). This can be attenuated using free radical scavengers and/or antioxidants.
Methods
Dox‐exposed cardiac myoblasts (H9c2 cells) were treated with sesamol (12.5, 25 and 50 μm), a natural phenolic compound. Intracellular ROS inhibition, cell viability and analysis of antioxidant and biochemical markers such as superoxide dismutase, catalase, glutathione‐S‐transferase, glutathione peroxidase, reduced/oxidized glutathione, lipid peroxidation and protein carbonyl content were performed. The effect of sesamol treatment on the cytotoxic and genotoxic parameters was studied by monitoring the signalling proteins involved in the apoptotic pathway.
Key findings
Dox triggered cellular and genetic damage by increasing levels of intracellular ROS, thereby decreasing cell viability and increasing apoptosis. Sesamol reversed the cytotoxic and genotoxic effects of Dox. In addition, sesamol attenuated the pro‐apoptotic proteins and improved the anti‐apoptotic status. Sesamol pre‐treatment also alleviated the disturbed antioxidant milieu by preventing ROS production and improving endogenous enzyme levels.
Conclusions
Among the different doses tested, 50 μm of sesamol showed maximum protection against Dox‐induced oxidative damage. This reflects the significance of sesamol in ameliorating the deleterious effects associated with cancer chemotherapy.