Effects of N(G)-nitro-L-arginine methyl ester on endotoxin-induced leakage of lactate dehydrogenase and cytotoxicity in J774A.1 cells.
In the present study, we investigated the effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) on tissue injury or cytotoxicity caused by endotoxin challenge by assaying lactate dehydrogenase (LDH) isozymes and cell viability in J774A.1 cells. In mice treated with L-NAME (10 mg kg(-1), i.v.), the activity of LDH in serum 18 h after endotoxin (6 mg kg(-1), i.p.) injection was not significantly different from that in mice treated with endotoxin alone. Mice injected with endotoxin exhibited leakage of LDH isozymes 3 and 5, but L-NAME did not protect against endotoxin-induced acute leakage of LDH isozymes. Treatment with L-NAME (10-1000 microM) significantly inhibited NO generation by endotoxin (1 microg ml(-1))-activated J774A.1 cells. However, L-NAME (10-1000 microM) did not affect endotoxin-induced cytotoxicity in J774A.1 cells. These findings suggested that endotoxin-induced NO formation may not contribute to tissue injury or cytotoxicity caused by endotoxin.
First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, Sendai, Japan.
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Sakaguchi
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Furusawa
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Takayanagi
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Y
Takayanagi
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004731:Endotoxins / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012486:Salmonella typhimurium
D004731:Endotoxins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester