Abstract Details

Title Aliskiren and cytokine's expression in mdx mice

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-035

Objective Evaluate the aliskiren effect in mdx mice

Background Duchenne Muscular Dystrophy (DMD) is caused by the mutation of the dystrophin gene, responsible for the stability of sarcolemma. The renin angiotensin system (RAS) has been known to participate of fibrosis and inflammation’s mechanism. Aliskiren, inhibitor of RAS, could reduce the inflammation and fibrosis in mdx mice.

Design/Methods 16 mdx mice (8-week-old) were selected. 8 were treated by saline solution 0,9% (group A) and 8 treated by aliskiren 25mg/kg/day (group B) by gavage during 5 weeks. The animals were weighed weekly, and muscle strength’s measure by the Kondziela method. After 5 weeks of treatment, creatine phosphokinase (CK) were dosed. Extensor digitorum longus (ELD), tibialis anterior (TA) and diaphragm (DIA) muscles were also collected for morphological analysis (internal nucleus count and Feret’s diameter). RT- PCR gene expression of myostatin, osteopontin, dystrophin, utrophin, TGF-β1 and TNF-αwere performed.

Results

We did not observe significant difference in mice weights, CK level and muscle strength. Morphological analysis showed a significant difference(p<0.05) in relation to Feret’s diameter in TA muscle. The treated group showed a smaller number of fibers with normal size. TGF-β1 was reduced in EDL and DIA muscles (treated group). Osteopontin was significantly elevated in EDL and DIA muscles and TNF- αwas significantly increased just in DIA muscle (treated group). Utrophin showed a significant increase in the DIA muscle (treated group).

Conclusions

Morphological findings were not significant in treated group. More important, Aliskiren did not demonstrate a reduction in fiber diameter in DIA muscle. Although we obtained different results for different cytokines for each muscle, Aliskiren reduced the TFG-β1 in 2 muscles, DIA and EDL evidencing its anti-fibrotic profile, suggesting that could act as a protector drug particularly for respiratory muscle. The utrophin increase could suggest that this protein may serve as a functional substitute for the dystrophin protein.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Giuliana Petri	No disclosure on file
	No disclosure on file
	No disclosure on file
Alzira A. Carvalho, MD (FMABC)	No disclosure on file

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