Platonin, a Photosensitizing Dye, Improves Circulatory Failure and Mortality in Rat Models of Endotoxemia

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概要

• 論文の詳細を見る

• Platonin, a cyanine photosensitizing dye, is a potent macrophage-activating agent and an immunomodulator. In this study, we compare the inhibitory effects of platonin with those of the three clinical drugs minocycline, clindamycin, and cyclosporin, on hypotension, tachycardia, and nitric oxide (NO) formation in a rat model of circulatory shock induced by Escherichia coli lipopolysaccharide (LPS). We also evaluate the effect of drugs on the 6h survival rate in LPS-treated rats. Administration of LPS (15mg/kg) caused a rapid drop in mean arterial blood pressure (MAP). Minocycline (10mg/kg, i.v.) significantly prevented the fall of MAP at 3h, and platonin (100 μg/kg, i.v.) markedly prevented the fall of MAP within the 0-3 h period after LPS administration. However, neither clindamycin (10 mg/kg, i.v.) nor cyclosporin (15 mg/kg, i.v.) had any effects in this study. On the other hand, an inducible NO synthase inhibitor, N_G-nitro-L-arginine ester (L-NAME), caused a significantly increase in MAP and a moderate bradycardia after LPS administration. In addition, an increase in plasma nitrate formation elicited by endotoxemia was significantly reduced by pretreatment with either minocycline (10 mg/kg) or platonin (100μg/kg). However, only platonin (100μg/kg) markedly reduced the mortality and prolonged the mean survival time in LPS-treated rats. Minocycline, clindamycin, and cyclosporin had no effects under the same conditions. Further studies using an electron spin resonance (ESR) method were conducted on the scavenging activity of platonin on the free radicals formed. Platonin (10 μM) greatly reduced the ESR signal intensity of superoxide anion, hydroxyl radical, and methyl radical formation. In conclusion, platonin has beneficial effects on ameliorating endotoxaemia. This protective effect of platonin may be mediated, at least partly, by the reduced drop in MAP and the inhibition of NO and free radical formation in rat models of endotoxemia.

• 社団法人日本薬学会の論文
• 2002-08-01

著者

• Sheu Joen-rong

  Department Of Pharmacology Thipei Medical University:graduate Institute Of Medical Sciences Taipei M

• Sheu Joen-rong

  台湾

• HSIAO George

  Department of Pharmacology, Taipei Medical University

• LFE Ji-Jen

  Department of Surgery Mackay Memorial Hospital

• CHOU Duen-Suey

  Department of Pharmacology, Thipei Medical University

• FONG Tsorng-Harn

  Graduate Institute of Medical Sciences, Taipei Medical University

• SHEN Ming-Yi

  Graduate Institute of Medical Sciences, Taipei Medical University

• LIN Chien-Huang

  Graduate Institute of Medical Sciences, Taipei Medical University

• Shen Ming-yi

  Graduate Institute Of Medical Sciences Taipei Medical University

• Hsiao G

  Taipei Medical Univ. Taipei Twn

• Hsiao George

  Department Of Pharmacology Taipei Medical University

• Chou Duen-suey

  Department Of Pharmacology Thipei Medical University

• Lin C‐h

  National Cheng Kung Univ. Tainan Twn

• Lin Chien-huang

  Graduate Institute Of Medical Sciences Taipei Medical University

• Fong Tsorng-harn

  Graduate Institute Of Medical Sciences Taipei Medical University

• Lin Chien-huang

  Graduate Institute Of Medical Sciences College Of Medicine Taipei Medical University

• Lee Ji-Jen

  Department of Surgery Mackay Memorial Hospital

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• Antithrombotic Effects of Magnesium Sulfate in In Vivo Experiments
• Platonin, a Photosensitizing Dye, Improves Circulatory Failure and Mortality in Rat Models of Endotoxemia
• The Protective Effects of PMC against Chronic Carbon Tetrachloride-Induced Hepatotoxicity in Vivo
• A Novel Cytotoxic C-Methylated Biflavone from the Stem of Cephalotaxus wilsoniana
• Antithrombotic Effects of Tetramethylpyrazine in In Vivo Experiments
• Elevated Expression of Connective Tissue Growth Factor in Human Atrial Fibrillation and Angiotensin II-Treated Cardiomyocytes

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