The glycine analogue, aminomethanesulfonic acid, inhibits LPS-induced production of TNF-alpha in isolated rat Kupffer cells and exerts hepatoprotective effects in mice.
The activation of Kupffer cells represents a central mechanism of liver injury involving the production of TNF-alpha. It is known that glycine prevents LPS-induced production of TNF-alpha in isolated Kupffer cells. In this study, the possibility that glycine analogues might affect Kupffer cells was investigated. As a result, aminomethanesulfonic acid (AMS) inhibited the production of TNF-alpha in LPS-stimulated Kupffer cells. Furthermore, LPS treatment caused a transient increase in intracellular calcium ([Ca(2+)](i)) which was blunted by AMS. Thus, the addition of AMS is protective against the LPS-induced increase [Ca(2+)](i) and subsequent production of TNF-alpha. Moreover, in vivo studies demonstrated that pretreatment of mice with AMS increased the rate of survival after injection with LPS/d-gal and reduced the TNF-alpha serum level and the mRNA level in the liver. These results indicate that intake of AMS attenuates the LPS-induced hepatotoxicity resulting from activation of Kupffer cells.
Pharmaceutical Research Laboratories, AJINOMOTO Co., Inc. 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan. sonoko_ishizaki@ajinomoto.com
Sonoko
S
Ishizaki-Koizumi
Ichiro
I
Sonaka
Yoshiyuki
Y
Takei
Kenichi
K
Ikejima
Nobuhiro
N
Sato
D000818:Animals; D005688:Galactosamine / Q000378:metabolism / Q000633:toxicity; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D051381:Rats; D013451:Sulfonic Acids / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D013451:Sulfonic Acids; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; C045904:aminomethanesulfonic acid; D005998:Glycine