title: Effects of the anti-sepsis drug, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD-712), on mortality, inflammation, and organ injuries in rodent sepsis models.
abstract: CKD-712 is a 1-naphthyl analog of higenamine that has been reported to have potent antiinflammatory and thus anti-sepsis effects. The purpose of this study was to investigate the potential of CKD-712 as a medicine for sepsis and to confirm its protective effects on organs in animal sepsis models. Pretreatment with CKD-712 dose-dependently increased survival rate in a lipopolysaccharide-induced sepsis model in mice. Body temperature decrease, an important pre-symptom of septic death, was also prevented by CKD-712. CKD-712 still significantly increased survival rate even when administered one and four hours after lipopolysaccharide injection. Therapeutic efficacy of CKD-712 was also confirmed against sepsis following zymosan-induced endotoxemia and in cecal ligation and puncture surgery in mice. In a disseminated intravascular coagulation model in rats, CKD-712 showed organ-protective effect by reducing serum glutamate-oxaloacetate transaminase, glutamate-pyruvate transferase, blood urea nitrogen, and creatinine levels. CKD-712 also prevented histological damage to the lung and liver. In this same model, CKD-712 showed anti-inflammatory effects through decreases in tumor necrosis factor-α and interleukin-6 in the blood and reduced translocation of nuclear factor-κB to the nuclei of lung cells. CKD-712 administration also diminished infiltration of leukocytes into the lung and liver. Taken together, these results show that CKD-712 has excellent potential as an effective medicine for sepsis.
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., Chonan, Korea.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: In-Chang
authors.initials: IC
authors.lastname: Hwang
authors.forename: Nina
authors.initials: N
authors.lastname: Ha
authors.forename: Sera
authors.initials: S
authors.lastname: Lee
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Sung Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: Hosung
authors.initials: H
authors.lastname: Yu
authors.forename: In-Taek
authors.initials: IT
authors.lastname: Lim
authors.forename: Jun-A
authors.initials: JA
authors.lastname: You
authors.forename: Dal-hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019446:Endotoxemia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D005334:Fever / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D044005:Tetrahydroisoquinolines; C090309:YS 49; D015054:Zymosan