Agomelatine Increases Muscle Strength And Reduces The Expression Of Inflammatory Cytokines In mdx Dystrophic Mice (P7.097)

Abstract

OBJECTIVE: Based on the antioxidant and anti-inflammatory properties of melatonin in DMD patients we decided to study agomelatine action in mdx mouse. BACKGROUND: The new antidepressant agomelatine is an agonist of melatonergic MT₁/ MT₂ receptors as well as an antagonist of serotonergic 5-HT2C receptors. Among the pathogenic mechanisms proposed for DMD, oxidative stress and inflammation are directly involved in the dystrophic process. DESIGN/METHODS: The study was conducted in male mdx with life 69.5 days (average of 31-114 days). The animals were maintained with food and water ad libitum. They were divided into two groups: Control (n = 22), agomelatine (n = 22). The first group received saline by gavage and the second one received agomelatine 30 mg /kg / day by gavage. The animals underwent treadmill exercise motorized 5 times / week, 18 cm / s for 10 min. Muscle strength was measured weekly. After five weeks, the diaphragm muscle was removed. Gene expression of TGF beta 1, TNF, and osteopontin were performed in muscle by real time PCR. RESULTS: Agomelatine’s group had a significant increase in muscle strength after 5 weeks treatment. The values of the measured cytokines were as follows:TGF beta1: Control (n=16)/Agomelatine (n=15):1,42 ±0,12/ 1,32 ± 0,17, p=0,05; TNF alpha: Control (n=16)/ Agomelatine(n=15): 1,46 ± 0,11; 1,36 ± 0,16,p=0,04; Osteopontine: Control (n=16)/ Agomelatine (n=15): 1,36 ± 0,11/1,26 ± 0,12, p=0.02. CONCLUSIONS: The anti-inflammatory action of melatonin is accompanied by a reduction of proinflammatory cytokines such as IL-1b, IL-6, TNF-a and interferon (INF)-c in reducing oxidative stress and also increases IGF-I preventing muscle atrophy in mdx mice castrated. The study demonstrated that agomelatine reduce the expression of inflammatory cytokines and increase muscle strength in mdx mice, which could be an alternative option for the treatment of muscular dystrophy.

Disclosure: Dr. Carvalho has nothing to disclose. Dr. Tondato has nothing to disclose. Dr. Iamnhuk has nothing to disclose. Dr. Gomiero has nothing to disclose. Dr. Petri has nothing to disclose. Dr. Delgado has nothing to disclose. Dr. Alves has nothing to disclose. Dr. Fonseca has nothing to disclose. Dr. Feder has nothing to disclose.