Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide release.
Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg(-1), i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO2- plus NO3-). Pretreatment with ethanol extract of E. rutaecarpa (25, 50 and 100 mg kg(-1), i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats. A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg(-1), i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia.
Chiou
Wen Fei
WF
National Research Institute of Chinese Medicine, NO. 155-1, SEC. 2, Li-Nung Street, Shipai, Taipei, Taiwan. wfchiou@cma23.nricm.edu.tw
Ko
Han Chieh
HC
Chen
Chieh Fu
CF
Chou
Cheng Jen
CJ
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D032086:Evodia; D005638:Fruit / Q000737:chemistry; D006146:Guanidines / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010656:Phenylephrine / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004731:Endotoxins; D006146:Guanidines; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; C004479:pimagedine