title: Effect of nitric oxide synthase inhibitors on lipid peroxide formation in liver caused by endotoxin challenge.
abstract: This study investigated the effect of nitric oxide on lipid peroxide formation during endotoxaemia. Nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine acetate (L-NMMA, 20 mg/kg, intravenously), N(G)-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, intravenously), and N(G)-nitro-L-arginine (L-NA, 10 mg/kg, intravenously), and a relatively selective inducible nitric oxide synthase inhibitor aminoguanidine (10 mg/kg, intravenously), did not protect against endotoxin-induced death of mice. Superoxide dismutase activity in liver 18 hr after administration of endotoxin (6 mg/kg, intraperitoneally) to L-arginine analogues (L-NMMA, L-NAME, L-NA)-treated mice was lower than in mice treated with endotoxin alone, whereas the administration of L-arginine analogues increased xanthine oxidase activity in the livers of endotoxin-injected mice compared with mice treated with endotoxin alone. In mice treated with L-arginine analogues and aminoguanidine, the levels of non-protein sulfhydryl and lipid peroxide in liver 18 hr after endotoxin injection did not show significant differences from mice treated with endotoxin alone. L-Arginine analogues and aminoguanidine had little effect on lipid peroxide formation in liver caused by endotoxin. Treatment with aminoguanidine (300 microM) significantly inhibited endotoxin-induced intracellular peroxide in J774A.1 cells, however, aminoguanidine did not affect endotoxin-induced cytotoxicity in J774A.1 cells. Our results clearly demonstrate that treatment with catalase (10 microg/ml), D-mannitol (10 mM), or superoxide dismutase (100 U/ml), has little or no effect on nitric oxide production by endotoxin (1 microg/ml)-activated J774A.1 cells. These findings suggest that nitric oxide is not crucial for lipid peroxide formation during endotoxaemia. Therefore, it is unlikely that nitric oxide plays a significant role in liver injury caused by free radical generation in endotoxaemia.
authors.affiliation: First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: S
authors.initials: S
authors.lastname: Furusawa
authors.forename: K
authors.initials: K
authors.lastname: Yokota
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Y
authors.initials: Y
authors.lastname: Takayanagi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004731:Endotoxins / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D008054:Lipid Peroxides / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015996:Survival Rate; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004731:Endotoxins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006146:Guanidines; D008054:Lipid Peroxides; D008070:Lipopolysaccharides; D013438:Sulfhydryl Compounds; D013481:Superoxides; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester