Inhibition of LPS-induced nitric oxide production in RAW cells by radioprotective thiols.
Nitric oxide (NO) is involved in producing damage after exposure to radiation and also in the toxicity associated with bacterial endotoxin (lipopolysaccharide, LPS). We have evaluated different radioprotective thiols for their effects on LPS-stimulated NO production in mouse macrophage cells, RAW 264.7. Our results indicate that although thiols inhibited NO production in general, the degree of inhibition depended upon the thiol compound. Long-chain aminothiols like WR-1065 [N-(2-mercaptoethyl)-1,3-diaminopropane] exerted a strong inhibition; but its parent drug, amifostine, which protects mice against radiation lethality, was not as effective as WR-1065. Diethyl dithiocarbamate, which is less effective than amifostine as a radioprotector, strongly inhibited NO production from macrophages. These results indicate that the radioprotective potential of sulfhydryl compounds is not related to its ability to inhibit NO production by macrophages and suggest that some of the thiol radioprotectors may effectively ameliorate the fatal symptoms of hypotensive shock, associated with endotoxin (LPS)-induced NO production.
Kumar
K Sree
KS
Radiation Casualty Management Team, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, Maryland 20889-5603, USA. kumar@afrri.usuhs.mil
Singh
Vijay K
VK
Jackson
William
W
Seed
Thomas M
TM
D000111:Acetylcysteine / Q000494:pharmacology; D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003545:Cysteine / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008624:Mercaptoethylamines / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D008070:Lipopolysaccharides; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D009569:Nitric Oxide; D003545:Cysteine; D004999:Amifostine; D004229:Dithiothreitol; D004221:Disulfiram; D000111:Acetylcysteine