Document Detail

Short-term exercise worsens cardiac oxidative stress and fibrosis in 8-month old db/db mice by depleting cardiac glutathione.
MedLine Citation:
PMID:  23039789     Owner:  NLM     Status:  Publisher    
Abstract Moderate exercise improves cardiac antioxidant status in young humans and animals with type 2 diabetes (T2D). Given that both diabetes and advancing age synergistically decrease antioxidant expression in most tissues, it is unclear whether exercise can upregulate cardiac antioxidants in chronic animal models of T2D. To this end, 8-month old T2D and normoglycemic mice were exercised for 3 weeks, and cardiac redox status evaluated. As expected, moderate exercise increased cardiac antioxidants and attenuated oxidative damage in normoglycemic mice. In contrast, similar exercise protocol in 8-month old db/db mice worsened cardiac oxidative damage, which was associated with a specific dysregulation of glutathione (GSH) homeostasis. Expression of enzymes for GSH biosynthesis [γ-glutamylcysteine synthase, glutathione reductase] as well as GSH-mediated detoxification (glutathione peroxidase, glutathione-S-transferase) were lower while toxic metabolites dependent on GSH for clearance (4-hydroxynonenal) were increased in exercised diabetic mice hearts. To validate GSH loss as an important factor for such aggravated damage, daily administration of GSH restored cardiac GSH levels in exercised diabetic mice. Such supplementation attenuated both oxidative damage and fibrotic changes in the myocardium. Expression of transforming growth factor beta (TGF-β) and its regulated genes responsible for such profibrotic changes were also attenuated with GSH supplementation. These novel findings in a long term T2D animal model demonstrates that short-term exercise by itself can deplete cardiac GSH and aggravate cardiac oxidative stress. As GSH administration conferred protection in 8-month old diabetic mice undergoing exercise, supplementation with GSH enhancing agents may be beneficial in elderly diabetic patients undergoing exercise.
Ismail Laher; Julianne Beam; Amy Botta; Rebekah Barendregt; Dian Sulistyoningrum; Angela Devlin; Mark Rheault; Sanjoy Ghosh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Free radical research     Volume:  -     ISSN:  1029-2470     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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