Protection against septic shock in mice with SJC13, an azaindolidine derivative that is a cell adhesion molecule inhibitor.
An azaindolidine derivative, SJC13, selectively inhibits expression and mRNA synthesis of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). The present experiments were performed to determine the in vivo effects of SJC13 against the lethality of LPS. In a mouse model of septic shock, intravenous administration of SJC13 5 min prior to LPS injection prevented significantly the lethality at doses of 3 mg/kg and 10 mg/kg. The prophylactic effect was dose-dependent. When injected up to 1 h after LPS injection, SJC13 inhibited significantly the lethality. Neutrophil emigration into lung tissues during sepsis induced with LPS, as assessed by lung myeloperoxidase (MPO) content and histological examination, was significantly prevented by SJC13 administration. These data demonstrate that SJC13 has therapeutic anti-inflammation potential in vivo.
Sakai
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Research Laboratory, Zenyaku Kogyo Co., Ltd., Tokyo, Japan.
D000818:Animals; D015815:Cell Adhesion Molecules; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects; D012772:Shock, Septic / Q000517:prevention & control*
D015815:Cell Adhesion Molecules; D007093:Imidazoles; D008070:Lipopolysaccharides; C102823:SJC 13