Protective effect of neurotropin against lipopolysaccharide-induced hypotension and lethality linked to suppression of inducible nitric oxide synthase induction.
Neurotropin is a non-protein extract from the dermis of rabbits inoculated with vaccinia virus and has been clinically used as an analgesic in Japan. We present in the current report evidence for its potential therapeutic value against endotoxin shock. Administration of this compound prior to lipopolysaccharide (LPS) challenge resulted in a reversal of a decrease of the mean arterial pressure in rats and also amelioration of lethality in mice. Anti-inducible nitric oxide synthase (iNOS) Western blotting of tissue extracts from LPS-treated mice revealed almost complete suppression of iNOS induction by Neurotropin. The findings in vivo were reproduced in in vitro experiments in which cultured human umbilical vascular endothelial cells were challenged with LPS. Simultaneous treatment of the cells with Neurotropin resulted in complete suppression of iNOS induction and significant reduction of cell death. These results suggested a therapeutic value of Neurotropin in the treatment of endotoxin shock that was linked, at least in part, to suppression of iNOS induction and reduced cell damage in vascular endothelial cells.
Higaki
A
A
Department of Neurobiology, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, Japan. higaki@grape.med.tottori-u.ac.jp
Ninomiya
H
H
Saji
M
M
Maki
H
H
Koike
T
T
Ohno
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004790:Enzyme Induction; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D011134:Polysaccharides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344
D008070:Lipopolysaccharides; D011134:Polysaccharides; C010491:neurotropin; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat