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 inj ury or cytotoxicity caused by endotoxin challenge by assaying lactate dehyd rogenase (LDH) isozymes and cell viability in J774A.1 cells. In mice treate d 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 fr om 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 again st endotoxin-induced acute leakage of LDH isozymes. Treatment with L-NAME ( 10-1000 muM) significantly inhibited NO generation by endotoxin (1 mug ml(- 1))-activated J774A.1 cells. However, L-NAME (10-1000 muM) did not affect e ndotoxin-induced cytotoxicity in J774A.1 cells. These findings suggested th at endotoxin-induced NO formation may not contribute to tissue injury or cy totoxicity caused by endotoxin. (C) 2001 Federation of European Microbiolog ical Societies. Published by Elsevier Science B.V. All rights reserved.