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
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- https://www.elsevier.com/tdm/userlicense/1.0/
- DOI
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- 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
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- Surgery
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Surgery 125 (4), 421-430, 1999-04
Elsevier BV
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キーワード
- Lipopolysaccharides
- Male
- Mice, Inbred ICR
- Nitrates
- L-Lactate Dehydrogenase
- Anti-Inflammatory Agents
- NF-kappa B
- Alanine Transaminase
- Blotting, Northern
- Methylprednisolone
- Antioxidants
- Gene Expression Regulation, Enzymologic
- Enzyme Activation
- Mice
- Liver
- Leukocytes, Mononuclear
- Animals
- Aspartate Aminotransferases
- Lipid Peroxidation
- DNA Probes