Effect of lazaroid U-74389G and methylprednisolone on endotoxin-induced shock in mice

書誌事項

公開日
1999-04
権利情報
  • https://www.elsevier.com/tdm/userlicense/1.0/
DOI
  • 10.1016/s0039-6060(99)70010-3
  • 10.1067/msy.1999.96394
公開者
Elsevier BV

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説明

Lazaroids are nonglucocorticoid analogs of methylprednisolone with multiple actions. We investigated whether lazaroid U-74389G could attenuate endotoxin-induced liver injury. We hypothesized that U-74389G treatment may protect against hepatic injury by suppressing proinflammatory gene up-regulation through inhibition of activation of nuclear factor kappa B (NF-kappa B). We also compared the efficacy of U-74389G with methylprednisolone in endotoxin-induced liver injury.Lipopolysaccharide (Escherichia coli, 30 mg/kg given intraperitoneally) was administered to male ICR mice, and U-74389G (3 mg/kg intraperitoneally) or methylprednisolone (30 mg/kg intravenously) was administered simultaneously. Phosphate-buffered saline solution (0.15 mL intravenously) was administered to mice that served as a control group.U-74389G and methylprednisolone treatment significantly increased survival rates 48 hours after lipopolysaccharide injection and protected against lipopolysaccharide-induced liver injury in vivo, as indicated by the decreased hepatic lipid peroxidation, tumor necrosis factor-alpha, and inducible nitric oxide synthase messenger RNA formation, hepatic enzyme release, and neutrophil infiltration in the liver. U-74389G and methylprednisolone also showed inhibitory effects on NF-kappa B activation in the liver.These findings suggest that U-74389G can suppress proinflammatory gene up-regulation through inhibition of NF-kappa B activation and that it is a promising new antioxidant drug for the treatment of endotoxin shock.

収録刊行物

  • Surgery

    Surgery 125 (4), 421-430, 1999-04

    Elsevier BV

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