Investigating the Potential for Sulforaphane to Attenuate Gastrointestinal Dysfunction in mdx Dystrophic Mice

• Published in: Nutrients 2021-12, Vol.13 (12), p.4559
• Main Authors: Swiderski, Kristy, Read, Suzannah J, Chan, Audrey S, Chung, Jin D, Trieu, Jennifer, Naim, Timur, Koopman, René, Lynch, Gordon S
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Colon; Colon - pathology; Constipation; Corn; Corn oil; Diaphragm; Diaphragm (anatomy); Diaphragm - pathology; Diarrhea; Disease Models, Animal; Duchenne's muscular dystrophy; Dystrophy; Enzymes; Fibrosis; Fibrosis - metabolism; Gastrointestinal diseases; Gastrointestinal Diseases - drug therapy; Gastrointestinal Diseases - metabolism; Humans; In vivo methods and tests; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Intestine; Isothiocyanate; Isothiocyanates - pharmacology; Kinases; Large intestine; Male; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Motility; Muscle contraction; Muscle, Skeletal - metabolism; Muscles; Muscular dystrophy; Muscular Dystrophy, Duchenne - drug therapy; Muscular Dystrophy, Duchenne - metabolism; NF-E2-Related Factor 2 - metabolism; NRF2 protein; Oils & fats; Oxidative stress; Physiology; Proteins; Quality of life; Rodents; Skeletal muscle; Sulforaphane; Sulfoxides - pharmacology
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13124559

Gastrointestinal (GI) dysfunction is an important, yet understudied condition associated with Duchenne muscular dystrophy (DMD), with patients reporting bloating, diarrhea, and general discomfort, contributing to a reduced quality of life. In the mouse, the most commonly used mouse model of DMD, studies have confirmed GI dysfunction (reported as altered contractility and GI transit through the small and large intestine), associated with increased local and systemic inflammation. Sulforaphane (SFN) is a natural isothiocyanate with anti-inflammatory and anti-oxidative properties via its activation of Nrf2 signalling that has been shown to improve aspects of the skeletal muscle pathology in dystrophic mice. Whether SFN can similarly improve GI function in muscular dystrophy was unknown. Video imaging and spatiotemporal mapping to assess gastrointestinal contractions in isolated colon preparations from and C57BL/10 mice revealed that SFN reduced contraction frequency when administered ex vivo, demonstrating its therapeutic potential to improve GI function in DMD. To confirm this in vivo, four-week-old male C57BL/10 and mice received vehicle (2% DMSO/corn oil) or SFN (2 mg/kg in 2% DMSO/corn oil) via daily oral gavage five days/week for 4 weeks. SFN administration reduced fibrosis in the diaphragm of mice but did not affect other pathological markers. Gene and protein analysis revealed no change in Nrf2 protein expression or activation of Nrf2 signalling after SFN administration and oral SFN supplementation did not improve GI function in mice. Although ex vivo studies demonstrate SFN's therapeutic potential for reducing colon contractions, in vivo studies should investigate higher doses and/or alternate routes of administration to confirm SFN's potential to improve GI function in DMD.