Program and book of abstracts 1st conference

1 st Conference of European Academy for Molecular Hydrogen Research in Biomedicine “Hydrogen for Biomedicine“

Singal Pawan K.

Dr. Pawan Singal is a professor of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada. Dr. Singal completed his PhD in Physiology in 1974 from the University of Alberta and his DSc degree in 1994. Professor since 1990, Dr. Singal served as Associate Dean for the Faculty of Graduate Studies; Director, Institute of Cardiovascular Sciences, University of Manitoba; and holder of the Naranjan S. Dhalla Chair. Internationally known for his work on oxidative stress and heart failure due to doxorubicin, chronic pressure overload and myocardial ischemia/reperfusion. He has published more than 300 papers, has co-edited 32 books, and trained more than 100 students, fellows and visiting scientists. He has received more than 100 national and international awards. The University of Manitoba has established an award in his name called ‘Pawan K. Singal Award for Graduate Students in Cardiovascular Sciences’. His name has been added to the Wall of Fame in the University Centre at the University of Manitoba recognizing his outstanding teaching skills and research. Additionally, the University of Winnipeg has bestowed to him an Honorary Doctorate of Law. VITAMIN C MITIGATES DOXORUBICIN-INDUCED NITROSATIVE STRESS Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada BACKGROUND: Doxorubicin (Dox) is a successful antitumor antibiotic but its usage is limited by its cardiotoxicity. We have reported through multiple studies that the effect is medicated by oxidative stress. There is also evidence that an increase in inducible nitric oxide synthase (iNOS) and nitrosative stress may also be involved. METHODS: Calcium tolerant cardiomyocytes isolated from adult rat hearts were exposed to Dox with or without Vitamin C (Vit C) – a water soluble antioxidant, to test its mitigating effects on nitrosative stress. Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms and nitrosative stress were analyzed. Cytokines TNFα and IL-10 in these isolated cardiomyocytes were also followed. RESULTS: Dox increased the expression of iNOS and altered protein expression as well as activation of endothelial NOS (eNOS). These changes were prevented by Vit C. Dox induced increase in the ratio of monomeric/dimeric eNOS, promoted the production of O2-., which was prevented by Vit C by increasing the stability of dimeric form of eNOS. Dox caused a significant increase in the generation of superoxide radical (O2-.), peroxynitrite, and NO, and these effects of Dox were blunted by Vit C. The latter also protected against Dox-induced increase in TNFα as well as a reduction in IL-10. CONCLUSIONS: These data suggest that Vit C provides cardioprotection by reducing oxidative/nitrosative stresses via a modulation of Dox-induced increase in the NO levels and NOS activity. Mitigation of inflammatory processes and apoptosis as well as upregulation of Vit C transporters by Vit C treatment may also have contributed to these protective effects. This work was supported by a grant from the Tri-Council Funding and Research Manitoba.

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