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: Jae-Hwan Park, In-Chang Hwang, Nina Ha, Sera Lee, Jung Min Kim, Sung Sook Lee, Hosung Yu, In-Taek Lim, Jun-A You, Dal-hyun Kim
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 34 Issue 3 Pg. 485-94 (Mar 2011) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 21547682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Lipopolysaccharides
• Tetrahydroisoquinolines
• YS 49
• Zymosan

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, therapeutic use)
• Cytokines (blood, immunology)
• Disease Models, Animal
• Disseminated Intravascular Coagulation (drug therapy, immunology, pathology)
• Endotoxemia (drug therapy, immunology, pathology)
• Fever (drug therapy, immunology, pathology)
• Kidney (drug effects, pathology)
• Lipopolysaccharides (pharmacology)
• Liver (drug effects, pathology)
• Lung (drug effects, pathology)
• Male
• Mice
• Mice, Inbred ICR
• Rats
• Rats, Sprague-Dawley
• Sepsis (drug therapy, immunology, pathology)
• Survival Analysis
• Tetrahydroisoquinolines (administration & dosage, therapeutic use)
• Zymosan (pharmacology)