Premium
Effect of long term quercetin supplementation on dystrophic cardiac pathology in mdx/utrn +/‐ mice
Author(s) -
Ballmann Christopher,
Beyers Ronald,
Denney Thomas,
Selsby Joshua,
Quindry John
Publication year - 2015
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.29.1_supplement.1039.4
Subject(s) - duchenne muscular dystrophy , medicine , endocrinology , quercetin , cardiac function curve , mdx mouse , utrophin , dystrophin , biology , heart failure , antioxidant , biochemistry
Duchenne muscular dystrophy (DMD) causes cardiac dysfunction and up to 40% of deaths are attributable to cardiac pathologies. Novel interventions are needed to counter cardiac complications. Recent findings indicate that increased PGC‐1α activity increases utrophin expression, among other benefits, and attenuates disease pathology in dystrophic skeletal muscle. We tested the hypothesis that, quercetin, a SIRT‐1/PGC‐1α activator, would also protect cardiac muscle and alleviate cardiac performance complications in a mouse DMD model. Mdx/utrn +/‐ mice were randomly assigned to standard chow or a 0.2% quercetin enriched diets from 2‐10 months (n=8/group). Age matched C57 mice were fed a control diet. Hearts received 7T MRI to quantify cardiac function at 2 and 10 months of age. Findings confirmed that as compared to C57, mdx/utrn +/‐ mice exhibited diminished cardiac function in a time‐dependent fashion in that end diastolic volume increased at 10 months in both mdx/utrn +/‐ groups (p=0.001). Quercetin enrichment preserved ejection fraction (p<0.001), systolic wall thickness (p=0.006), and fractional shortening (p<0.001) at 10 months of age in mdx/utrn +/‐ mice compared to mdx/utrn +/‐ control fed mice. Quercetin enrichment attenuated increased end systolic volume at 10 months (p<0.001) in mdx/utrn +/‐ quercetin fed mice versus control‐fed mdx/utrn +/‐ mice. Data indicate that quercetin enrichment prevents the age‐dependent cardiac function decline in mdx/utrn +/‐ mice. Additional research should identify the underlying mechanisms and refine quercetin dosing strategies. Funded by Duchenne Alliance.