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Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species
Timo M Buetler1, Mathilde Renard, Elizabeth A Offord
1Pharmacology Group, School of Pharmacy, University of Lausanne, Switzerland.
Background:
Duchenne muscular dystrophy is a severe X-linked congenital disorder characterized by lethal muscle wasting caused by the absence of the structural protein dystrophin.
Objective:
Because generation of reactive oxygen species appears to play an important role in the pathogenesis of this disease, we tested whether antioxidant green tea extract could diminish muscle necrosis in the mdx mouse dystrophy model.
Design:
A diet supplemented with 0.01% or 0.05% green tea extract was fed to dams and neonates for 4 wk beginning on the day of birth. Muscle necrosis and regeneration were determined in stained cryosections of soleus and elongator digitorum longus muscles. Radical scavenging by green tea extract was determined in differentiated cultured C2C12 cells treated with tert-butylhydroperoxide, with the use of 2',7'-dichlorofluorescin diacetate as a radical detector.
Results:
This feeding regimen significantly and dose-dependently reduced necrosis in the fast-twitch muscle elongator digitorum longus but at the doses tested had no effect on the slow-twitch soleus muscle. Green tea extract concentration-dependently decreased oxidative stress induced by tert-butylhydroperoxide treatment of cultured mouse C2C12 myotubes. The lower effective dose tested in mdx mice corresponds to approximately equal to 1.4 L (7 cups) green tea/d in humans.
Conclusion:
Green tea extract may improve muscle health by reducing or delaying necrosis in mdx mice by an antioxidant mechanism.
Insights
Antioxidant green tea extract reduced muscle necrosis in Duchenne muscular dystrophy (DMD) mouse models by scavenging reactive oxygen species. This suggests a potential therapeutic benefit for DMD by improving muscle health.
Area of Science:
- Biochemistry
- Cell Biology
- Genetics
Background:
- Duchenne muscular dystrophy (DMD) is a severe X-linked disorder causing progressive muscle wasting due to dystrophin absence.
- Reactive oxygen species (ROS) play a significant role in DMD pathogenesis.
Purpose of the Study:
- To investigate if antioxidant green tea extract (GTE) can reduce muscle necrosis in the mdx mouse model of DMD.
- To assess the efficacy of GTE in mitigating oxidative stress associated with DMD.
Main Methods:
- Mdx mice and control dams were fed diets supplemented with 0.01% or 0.05% GTE for 4 weeks.
- Muscle necrosis and regeneration were quantified in cryosections of soleus and elongator digitorum longus (EDL) muscles.
- Radical scavenging activity of GTE was evaluated in cultured C2C12 myotubes exposed to tert-butylhydroperoxide.
Main Results:
- GTE significantly and dose-dependently reduced necrosis in fast-twitch EDL muscles but not in slow-twitch soleus muscles.
- GTE demonstrated concentration-dependent reduction of oxidative stress in cultured myotubes.
- The effective dose in mdx mice approximates 1.4 L (7 cups) of green tea daily for humans.
Conclusions:
- Green tea extract may offer a therapeutic strategy for DMD by reducing or delaying muscle necrosis.
- The antioxidant properties of GTE are likely responsible for its beneficial effects in the mdx mouse model.
