Tumor necrosis factor-alpha and nitric oxide production in endotoxin-primed rats administered carbon tetrachloride.
Tumor necrosis factor-alpha (TNF alpha) is elevated in the sera of rats administered non-lethal doses of carbon tetrachloride (CCl4) followed by endotoxin. Elevated TNF alpha levels are correlated with the increased release of hepatic enzymes indicating hepatic damage. Under these conditions, nitric oxide (NO) was also produced in the liver as evidenced by the formation of nitrosyl complexes which were measured by electron paramagnetic resonance (EPR) spectroscopy. Decreased nitrosyl complex formation occurred in livers following treatment with either an inhibitor or macrophage activation (gadolinium trichloride; GdCl3), an inhibitor of cytokine responses (dexamethasone) or a NO synthase inhibitor (NG-monomethyl-L-arginine; 1-NMA), GdCl3 or dexamethasone treatment decreased, while 1-NMA treatment increased, TNF alpha serum level. Taken together, these data suggest that TNF alpha and NO are induced following CCl4 and LPS exposure and may be important regulators in the hepatotoxicity of this liver injury model.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury; D003907:Dexamethasone / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D005682:Gadolinium / Q000494:pharmacology; D007700:Kinetics; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019323:omega-N-Methylarginine
D004731:Endotoxins; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D005682:Gadolinium; D002251:Carbon Tetrachloride; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C038958:gadolinium chloride