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Mitigation of nitrosative stress and inflammation by Vitamin C in cardiomyopathy
Author(s) -
Akolkar Gauri,
Bagchi Ashim K,
Silva Dias Danielle,
Angelis Katia,
Jassal Davinder,
Singal Pawan K
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.953.12
Subject(s) - peroxynitrite , oxidative stress , nitric oxide , in vivo , inflammation , pharmacology , vitamin c , doxorubicin , nitric oxide synthase , reactive nitrogen species , antioxidant , reactive oxygen species , chemistry , vitamin e , medicine , heart failure , in vitro , biochemistry , chemotherapy , biology , superoxide , enzyme , microbiology and biotechnology
Background Oxidative/nitrosative stress is being linked as a key event in development of various cardiovascular diseases. Increase in the generation of reactive oxygen and nitrogen species is considered as a major trigger for cellular and tissue injury in the heart leading to myocardial dysfunction in general and doxorubicin (Dox) ‐ induced heart failure in particular. Previously we have shown that Vitamin C (Vit C), a very potent antioxidant, reduced Dox‐induced oxidative stress in isolated cardiomyocytes. However the role of Vit C in mitigation of cardiac nitrosative stress and inflammation needs to be understood. The aim of present study is to understand role of Vit C on cardiac nitrosative stress and inflammation. Methods Cardiomyocytes isolated from adult Sprague‐Dawley rats were treated with predetermined doses of Vit C (25 μM), Dox (10 μM) or Vit C (25 μM) + Dox (10 μM) for in vitro studies. To understand the effect of Vit C in vivo, adult male Wistar rats were treated with Vit C (50 mg/kg bw orally daily) for 6 weeks or Dox (15mg/kg bw given intraperitoneally in six equal doses for three weeks) or combination treatment with Vit C + Dox. At the end of 6 weeks, animals were euthanized and hearts and blood were collected for further analysis. Results Dox treatment increased levels of peroxynitrite in isolated cardiomyocytes and this effect was significantly reduced by Vit C co‐treatment. Both invitro and invivo, Dox induced an increase in levels of Nitric oxide, Nitric oxide synthase (NOS) activity and protein nitrosylation. These in vitro and invivo effects were blocked by Vit C. Dox caused an increased protein expression of inducible NOS which was prevented by Vit C, whereas expression of endothelial NOS was reduced. Treatment with Dox showed increase in levels of inflammatory cytokine TNFα and a decrease in the anti‐inflammatory cytokine IL10. Vit C co‐treatment prevented deleterious effects of Dox by reduction in levels of TNFα and increased levels of IL10. Conclusion Based on these results, it is suggested that an attenuation of major triggers of Dox‐induced cardiotoxicity by Vit C would be beneficial in protecting the heart from cardiac side effect of chemotherapy. Support or Funding Information CIHR and GETS, University of Manitoba.