In vivo spin trapping of nitric oxide generated in the small intestine, liver, and kidney during the development of endotoxemia: a time-course study.
Spin trapping of nitric oxide (NO.) in vivo in liver, small intestine, kidney, and plasma of intact rats was accomplished using diethyldithiocarbamate (DETC) administered intraperitoneally. DETC combines with Fe2+ to form (DETC)2-Fe and is an excellent trapping agent for nitric oxide. DETC distribution and uptake by the organs of interest was determined and the formation of the active trapping agent (DETC)2-Fe was assayed in the various organs and plasma. The capacity of this spin trap to capture NO. in vivo was demonstrated by administering sodium nitroprusside to the animals. The trapping procedure was then used to assess the course of NO. generation during a 6 h period in animals that had been treated with endotoxin. The rate of NO. generation/gram tissue was determined during the last 15 min of each time period. The results indicate that induction of nitric oxide generation begins earliest in the small intestine, then in the liver, and still later in the kidney and plasma. Nitric oxide production was most intense in the liver and was still increasing at the end of the experiment. Control animals receiving the spin trapping agent showed only little or no evidence of nitric oxide production except for the small intestine. The results show that induction of NO. generation caused by endotoxin begins at different times in different organs.
Free Radical Biology and Aging Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
G
G
Wallis
D
D
Brackett
M
M
Lerner
Y
Y
Kotake
R
R
Bolli
P B
PB
McCay
D000818:Animals; D004050:Ditiocarb / Q000737:chemistry / Q000493:pharmacokinetics; D019446:Endotoxemia / Q000378:metabolism*; D004731:Endotoxins / Q000633:toxicity; D005290:Ferric Compounds / Q000737:chemistry; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013113:Spin Labels; D019097:Spin Trapping / Q000379:methods; D013997:Time Factors
D004731:Endotoxins; D005290:Ferric Compounds; D013113:Spin Labels; D009569:Nitric Oxide; C025314:ferric citrate; D004050:Ditiocarb