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Effect of chronic quercetin supplementation on dystrophic cardiac pathology in mdx mice (LB672)
Author(s) -
Ballmann Christopher,
Hollinger Katrin,
Quindry John,
Selsby Joshua
Publication year - 2014
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.28.1_supplement.lb672
Subject(s) - medicine , duchenne muscular dystrophy , h&e stain , fibrosis , sod2 , mitochondrial biogenesis , cardiac fibrosis , mdx mouse , dystrophin , endocrinology , inflammation , pathology , immunohistochemistry , mitochondrion , biology , oxidative stress , superoxide dismutase , microbiology and biotechnology
Duchenne Muscular Dystrophy (DMD) includes cardiac complications with 10‐40% of deaths resulting from cardiac pathologies. In absence of a cure, we are exploring clinically viable interventions to counter cardiac complications associated with DMD. Quercetin (Q) is a SIRT‐1/PGC‐1α activator that up‐regulates antioxidant genes, mitochondrial biogenesis, and decreases inflammation when taken by nutraceutical means. Thus, we investigated 0.2% Q dietary enrichment to counter cardiac abnormalities in mdx mice, a widely used model for DMD. Mice were randomly treated from either 3 weeks or 3 months for a 6 month intervention (3w6m or 3m6m, n=10/group). Control (C) mice consumed rodent chow for equal time periods (n=10/group). At the end of the study, hearts were excised, weighed, and frozen (‐80 C°), cut into 10µm sections for immunohistochemistry, or prepped for western blotting (WB). Body weight did not change. Relative and absolute heart weights were decreased in Q3m6m mice (p=.03,p=.021). WB targets for mitochondrial biogenesis (Cytochrome C, p=.045) and antioxidant expression (SOD2, p=.012) were increased in Q3w6m mice. Indications of remodeling and fibrosis (MMP9, p=.043, hematoxylin and eosin, p=.001) were improved in Q‐fed mice while TGFβ‐1 expression was unchanged. 6 months of Q feeding improved long term markers and appears to effectively attenuate dystrophic cardiac pathology. Based on findings from younger mice, improvement in mitochondrial content and antioxidant activity may precede these outcomes. Results reveal a promising intervention to complications of dystrophic cardiac pathology. Additional experiments are needed to confirm these findings with more reductionist approaches.