Effect of Immunosuppressants on Lipopolysaccharide-Induced Changes of Nitric Oxide Synthase Activity in Liver and Brain of Mice

면역억제제가 Lipopolysaccharide에 의한 생쥐의 간 및 뇌조직의 Nitric Oxide Synthase 활성도의 변화에 미치는 영향

  • Min, Byung-Woo (Department of Orthopedic Surgery, School of Medicine, Keimyung University) ;
  • Han, Hyng-Soo (Department of Pharmacology, School of Medicine, Kyungpook National University) ;
  • Park, Jung-Sook (Department of Pharmacology, School of Medicine, Kyungpook National University) ;
  • Kim, Choong-Young (Department of Pharmacology, School of Medicine, Kyungpook National University)
  • 민병우 (계명대학교 의과대학 정형외과학교실) ;
  • 한형수 (경북대학교 의과대학 약리학교실) ;
  • 박정숙 (경북대학교 의과대학 약리학교실) ;
  • 김중영 (경북대학교 의과대학 약리학교실)
  • Published : 1995.09.30

Abstract

To verify the effect of immunosuppressants on the endotoxin-induced increase in iNOS activity, the action of immunosuppressants, dexamethasone (1.5 mg/kg), azathioprine (5 mg/kg/day) and cyclosporine (10 mg/kg), were evaluated in mice pretreated with LPS. The intraperitoneal injection of lipopolysaccharide (10 mg/kg) increased the nitric oxide synthase (NOS) activity in the brain and liver to maximum at 1 and 3 hours, respectively. The increase in NOS activity was blocked by the treatment with NOS inhibitor, LNAME(300 mg/kg) and aminoguanidine(100 mg/kg); a protein inhibitor, cycloheximide (10 mg/kg); and a transcription inhibitor of inducible NOS(iNOS), dexamethasone(1.5 mg/kg). Immunosuppressants, azathioprine (5 mg/kg) and cyclosporine (10 mg/kg), effectively blocked the increase in NOS activity. These results suggest that iNOS expression plays an important role in LPS-induced the increase in NOS activity and that immunosuppressants can be used as candidate for therapeutic agents in endotoxemia.

Keywords