Melatonin prevents endotoxin-induced circulatory failure in rats.
The pineal secretory product melatonin was found to exert protective effects in septic shock. In a host infected by bacterial lipopolysaccharide (LPS), the expression and release of proinflammatory tumor necrosis factor-alpha (TNF-alpha) is rapidly increased, suggesting that TNF-alpha is associated with the etiology of endotoxic shock. Recent reports show that the expression of NO synthase (NOS) II and the production of superoxide anion (O2*-) also contribute to the pathophysiology of septic shock. In the present study we demonstrate that melatonin prevents circulatory failure in rats with endotoxemia and improves survival in mice treated with a lethal dose of LPS. The beneficial hemodynamic effects of melatonin in the endotoxemic animal appear to be associated with the inhibition of (i) the release of TNF-alpha in plasma, (ii) the expression of NOS II in liver, and (iii) the production of O2*- in aortae. In addition, the infiltration of polymorphonuclear neutrophils into the liver from the surviving LPS mice treated with melatonin was reduced. Thus, our results support the clinical use of melatonin in endotoxemia.
Wu
C C
CC
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. ccwu@ms36.url.com.tw
Chiao
C W
CW
Hsiao
G
G
Chen
A
A
Yen
M H
MH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic; D015153:Blotting, Western; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D019446:Endotoxemia / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D004926:Escherichia coli; D016166:Free Radical Scavengers / Q000494:pharmacology; D008070:Lipopolysaccharides; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D051381:Rats; D011921:Rats, Inbred WKY; D012772:Shock, Septic / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin