Sardine oil loaded vanillic acid grafted chitosan microparticles, a new functional food ingredient: attenuates myocardial oxidative stress and apoptosis in cardiomyoblast cell lines (H9c2)

Abstract

Fish oil has been widely recognized as an excellent dietary source of polyunsaturated n-3 fatty acids such as EPA and DHA. However, it can undergo oxidation easily resulting in the formation of toxic off flavor compounds such as hydroperoxides. These compounds adversely affect the nutritional quality and may induce several stress reactions in body. To solve this problem, a new antioxidant bio-material, vanillic acid-grafted chitosan (Va-g-Ch), was synthesized and used as a wall material for microencapsulation of fish oil. The sardine oil loaded Va-g-Ch microparticles could be a potential functional food ingredient considering the numerous health benefits of fish oil, chitosan, and vanillic acid. The current study aimed to investigate the possible protective effect of sardine oil-loaded Va-g-Ch microparticles against doxorubicin-induced cardiotoxicity and the underlying mechanisms. In vitro cytotoxicity evaluation was conducted using H9c2 cardiomyocytes. MTT assay revealed that effective cytoprotective effect was induced by a sample concentration of 12.5 μg/mL. Results of apoptosis by double fluorescent staining with acridine orange/ethidium bromide and caspase-3 evaluation by ELISA substantiated the above findings. Further, flow cytometric determination of membrane potential, relative expression of NF-κB by PCR, and ROS determination using DCFH-DA also confirmed the protective effect of encapsulated sardine oil against doxorubicin-induced cardiotoxicity. NF-κB expression was down-regulated nearly by 50% on cells treated with encapsulated sardine oil. Altogether, the results revealed that sardine oil-loaded Va-g-Ch microparticles demonstrated potential cell protection against doxorubicin-induced oxidative stress.

Protective Effects of ω-3 PUFA in Anthracycline-Induced Cardiotoxicity: A Critical Review

“…Moreover, one in vivo study [ 118 ] ( Table 1 ) did not investigate the functional/morphological effect on the heart, but reported the preventive effects that these fatty acids induced at biochemical and molecular levels in this area. Such beneficial effects were also reported by all the four in vitro studies [ 80 , 82 , 83 , 119 ] ( Table 2 ) conducted in cardiomyocytes treated with ω-3 PUFA and DOX.…”

“…Almost all the results related to the potential of ω-3 PUFA in preventing cardiac events induced by chemotherapy refer to the treatments with the ATC antibiotics [ 78 , 79 , 80 , 81 , 82 , 83 ]. The possibility to prevent ATC-induced cardiotoxicity is a field of great interest, since this class of drugs is still the most extensively used in a variety of human solid and hematological cancers (e.g., breast cancer, sarcoma, lymphoma and pediatric leukemia) in combination with other categories of conventional chemotherapeutic agents or new-generation targeted drugs [ 15 ].…”

“…Moreover, two in vitro investigations ( Table 2 ) [ 80 , 82 ] found that EPA and DHA added to the culture medium had the potential to suppress the DOX-induced ROS production of H9C2 cardiomyoblast cell line. It was also found that the treatment of cardiomyoblasts in vitro with DHA [ 82 ] or sardine oil embedded in vanillic acid-chitosan microparticles [ 83 ] could also suppress the DOX-induced expression/activation of NF-κB [ 82 , 83 ], a transcription factor activated by the increase of ROS at the cellular level, and, furthermore, involved in the transcription of inflammatory cytokines. Compatibly, DHA was also found to suppress [ 82 ] the DOX-induced expression of TNF-α, IL-6, MCP-1 and IL-1β.…”

“…In the same work [ 82 ] DHA also reduced the DOX-mediated expression of the enzyme iNOS, related to the generation of the powerful oxidant peroxynitrite from NO. Some of these in vitro studies ( Table 2 ) reported the contrasting effect exerted by ω-3 treatment on phenomena related to the DOX-induced apoptosis, i.e., the decrease of the mitochondrial membrane potential, and caspase-3 activation [ 80 , 83 ]. Lastly, one of these studies reported the ω-3 ability to suppress the increase in (Ca 2+ ) i related to the alteration induced by DOX in sarcoplasmic reticulum Ca 2+ release [ 119 ].…”

Two novel anticancer compounds with minimum cardiotoxic property

“…Rate of cardiovascular diseases (CVDs) remains number one of the fatal diseases, which is ever increasing worldwide and hence, scienti c community has concerned about it [1,2]. Cardiotoxicity occurs as a result of the complicated working of cardiac cells and tissues or due to a chemical molecule affecting heart function and structure [3,4].…”