Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 371, Issue 1, pp 34–43

Thaliporphine increases survival rate and attenuates multiple organ injury in LPS-induced endotoxaemia

  • Chin-Wei Chiao
  • Shoei-Sheng Lee
  • Chin-Chen Wu
  • Ming-Jai Su
Original Article

Abstract

This study addressed the question of whether thaliporphine, a phenolic aporphine alkaloid obtained from Chinese herbs and possessing antioxidant and α-1 adrenoceptor antagonistic activity, has protective effects in endotoxaemic rats and we attempted to elucidate the mechanisms contributing to such protective effects. Injection of rats with endotoxin (E. coli lipopolysaccharide, LPS) induced severe hypotension and tachycardia as well as vascular hyporeactivity to noradrenaline. Pretreatment of LPS-treated rats with thaliporphine attenuated the delayed hypotension significantly whilst only a higher dose (1 mg/kg) of thaliporphine decreased LPS-induced tachycardia. LPS significantly increased nitric oxide (NO·) and superoxide anion (O2·) levels, a response that was reduced by pretreatment with 1 mg/kg thaliporphine. Endotoxaemia for 240 min resulted in a bell-shaped time course for the change of serum tumour necrosis factor-α (TNF-α) level with a peak at 60 min. Pretreatment of LPS-treated rats with 1 mg/kg thaliporphine significantly reduced the serum TNF-α level at 60 min. In addition, LPS caused a biphasic change in blood glucose and thaliporphine attenuated the late-phase decrease in blood glucose. Endotoxaemia induced multiple organ injury in the liver, kidney and heart, as indicated by increases of aspartate aminotransferase (GOT), alanine aminotransferase (GPT), creatinine (CRE), lactate dehydrogenase (LDH) and creatine phosphate kinase muscle-brain (CKMB) levels in serum. These increases of biochemical markers and inflammatory cell infiltration into injured tissues were reduced significantly by treatment with thaliporphine. In addition, thaliporphine increased the survival rate of LPS-treated mice dose-dependently. In conclusion, our results suggest that thaliporphine could be a novel agent for attenuating endotoxin-induced circulatory failure and multiple organ injury and may increase the survival rate. These beneficial effects of thaliporphine may be attributed to the suppression of TNF-α, NO· and O2· production.

Keywords

Lipopolysaccharide Thaliporphine Nitric oxide Superoxide anion Tumour necrosis factor-α Survival rate Multiple organ injury 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Chin-Wei Chiao
    • 1
  • Shoei-Sheng Lee
    • 2
  • Chin-Chen Wu
    • 3
  • Ming-Jai Su
    • 1
  1. 1.Institute of Pharmacology, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Department of Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  3. 3.Department of PharmacologyNational Defence Medical CentreTaipeiTaiwan

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