Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle
Introduction: It has been proposed that an increased susceptivity to oxidative stress caused by the absence of the protein dystrophin from the inner surface of the sarcolemma is a trigger of skeletal muscle necrosis in the destructive dystrophin deficient muscular dystrophies. Here we use the mdx mo...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1109587/full |
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| author | Asma Redwan Leonit Kiriaev Sindy Kueh John W. Morley Peter Houweling Ben D. Perry Stewart I. Head Stewart I. Head |
| author_facet | Asma Redwan Leonit Kiriaev Sindy Kueh John W. Morley Peter Houweling Ben D. Perry Stewart I. Head Stewart I. Head |
| author_sort | Asma Redwan |
| collection | DOAJ |
| description | Introduction: It has been proposed that an increased susceptivity to oxidative stress caused by the absence of the protein dystrophin from the inner surface of the sarcolemma is a trigger of skeletal muscle necrosis in the destructive dystrophin deficient muscular dystrophies. Here we use the mdx mouse model of human Duchenne Muscular Dystrophy to test the hypothesis that adding the antioxidant NAC at 2% to drinking water for six weeks will treat the inflammatory phase of the dystrophic process and reduce pathological muscle fiber branching and splitting resulting in a reduction of mass in mdx fast-twitch EDL muscles.Methods: Animal weight and water intake was recorded during the six weeks when 2% NAC was added to the drinking water. Post NAC treatment animals were euthanised and the EDL muscles dissected out and placed in an organ bath where the muscle was attached to a force transducer to measure contractile properties and susceptibility to force loss from eccentric contractions. After the contractile measurements had been made the EDL muscle was blotted and weighed. In order to assess the degree of pathological fiber branching mdx EDL muscles were treated with collagenase to release single fibers. For counting and morphological analysis single EDL mdx skeletal muscle fibers were viewed under high magnification on an inverted microscope.Results: During the six-week treatment phase NAC reduced body weight gain in three- to nine-week-old mdx and littermate control mice without effecting fluid intake. NAC treatment also significantly reduced the mdx EDL muscle mass and abnormal fiber branching and splitting.Discussion: We propose chronic NAC treatment reduces the inflammatory response and degenerative cycles in the mdx dystrophic EDL muscles resulting in a reduction in the number of complexed branched fibers reported to be responsible for the dystrophic EDL muscle hypertrophy. |
| first_indexed | 2024-04-10T15:17:27Z |
| format | Article |
| id | doaj.art-a181e69843b34752b923fd38b92ebb05 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-10T15:17:27Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-a181e69843b34752b923fd38b92ebb052023-02-14T18:09:08ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-02-011410.3389/fphys.2023.11095871109587Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscleAsma Redwan0Leonit Kiriaev1Sindy Kueh2John W. Morley3Peter Houweling4Ben D. Perry5Stewart I. Head6Stewart I. Head7School of Medicine, Western Sydney University, Sydney, NSW, AustraliaMurdoch Children’s Research Institute, Melbourne, VIC, AustraliaSchool of Medicine, Western Sydney University, Sydney, NSW, AustraliaSchool of Medicine, Western Sydney University, Sydney, NSW, AustraliaMurdoch Children’s Research Institute, Melbourne, VIC, AustraliaSchool of Science, Western Sydney University, Sydney, NSW, AustraliaSchool of Medicine, Western Sydney University, Sydney, NSW, AustraliaMurdoch Children’s Research Institute, Melbourne, VIC, AustraliaIntroduction: It has been proposed that an increased susceptivity to oxidative stress caused by the absence of the protein dystrophin from the inner surface of the sarcolemma is a trigger of skeletal muscle necrosis in the destructive dystrophin deficient muscular dystrophies. Here we use the mdx mouse model of human Duchenne Muscular Dystrophy to test the hypothesis that adding the antioxidant NAC at 2% to drinking water for six weeks will treat the inflammatory phase of the dystrophic process and reduce pathological muscle fiber branching and splitting resulting in a reduction of mass in mdx fast-twitch EDL muscles.Methods: Animal weight and water intake was recorded during the six weeks when 2% NAC was added to the drinking water. Post NAC treatment animals were euthanised and the EDL muscles dissected out and placed in an organ bath where the muscle was attached to a force transducer to measure contractile properties and susceptibility to force loss from eccentric contractions. After the contractile measurements had been made the EDL muscle was blotted and weighed. In order to assess the degree of pathological fiber branching mdx EDL muscles were treated with collagenase to release single fibers. For counting and morphological analysis single EDL mdx skeletal muscle fibers were viewed under high magnification on an inverted microscope.Results: During the six-week treatment phase NAC reduced body weight gain in three- to nine-week-old mdx and littermate control mice without effecting fluid intake. NAC treatment also significantly reduced the mdx EDL muscle mass and abnormal fiber branching and splitting.Discussion: We propose chronic NAC treatment reduces the inflammatory response and degenerative cycles in the mdx dystrophic EDL muscles resulting in a reduction in the number of complexed branched fibers reported to be responsible for the dystrophic EDL muscle hypertrophy.https://www.frontiersin.org/articles/10.3389/fphys.2023.1109587/fullmdxskeletal muscle contractionNACoxidative stressfiber branchingmuscle damage |
| spellingShingle | Asma Redwan Leonit Kiriaev Sindy Kueh John W. Morley Peter Houweling Ben D. Perry Stewart I. Head Stewart I. Head Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle Frontiers in Physiology mdx skeletal muscle contraction NAC oxidative stress fiber branching muscle damage |
| title | Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle |
| title_full | Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle |
| title_fullStr | Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle |
| title_full_unstemmed | Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle |
| title_short | Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle |
| title_sort | six weeks of n acetylcysteine antioxidant in drinking water decreases pathological fiber branching in mdx mouse dystrophic fast twitch skeletal muscle |
| topic | mdx skeletal muscle contraction NAC oxidative stress fiber branching muscle damage |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1109587/full |
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