Inibição da prostaglandina D sintetase diminui a necrose muscular

Japão - músculos de pacientes com distrofia muscular de Duchenne apresentam expressão da prostaglandina D sintetase. Nesta pesquisa em camundongos normais e camundongos com distrofia muscular os autores utilizaram a droga HQL-79, que inibe a prostaglandina D sintetase. Os autores observaram redução da inflamação e consequentemente da necrose muscular e também aumento de força nos camundongos com distrofia muscular.

O resumo em inglês pode ser lido abaixo:

(Am. J. Pathol., Apr 2009) Inhibition of prostaglandin D synthase suppresses muscular necrosis

Ikuko Mohri, Kosuke Aritake, Hidetoshi Taniguchi, Yo Sato, Shinya Kamauchi, Nanae Nagata, Toshihiko Maruyama, Masako Taniike, and Yoshihiro Urade - Japan

Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor 1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy .

Fonte: http://distrofiamuscular.net/noticias.htm