Evidence that aminoguanidine inhibits endotoxin-induced bacterial translocation.
BACKGROUND
The role of inducible nitric oxide synthase (iNOS) in endotoxin-induced bacterial translocation was investigated by using its specific blocker aminoguanidine in 46 albino mice (25-35 g) allocated into four groups.


METHODS
The first group received intraperitoneal saline (control; 0.9 per cent w v(-1) sodium chloride 1 ml kg(-1); n=6), the second group intraperitoneal endotoxin (Escherichia coli lipopolysaccharide 055:B5 20 mg kg(-1); n=19), the third group intraperitoneal aminoguanidine (20 mg kg(-1), 20 min before and 12 h after saline; n=6) and the fourth group both endotoxin and aminoguanidine intraperitoneally (n=15). Some 24 h later, the animals were anaesthetized with ether and blood samples were collected by cardiac puncture together with mesenteric lymph node (MLN), spleen and liver specimens under aseptic conditions. Specimens were then cultured to determine the presence of colony-forming units as an index of bacterial translocation.


RESULTS
No bacterial growth was detected in samples from the first and third groups. Colony-forming bacteria were found in ten of 14 MLN samples, eight of 14 spleens, four of 14 livers and three of 14 peripheral blood samples in the second group, with E. coli being the predominant pathogen. In contrast, in the fourth group, colony-forming bacteria were found in only three of 14 MLN samples (P=0.02 versus the second group), three of 14 spleens and one of 14 liver specimens. None of the values in the fourth group was significantly different from those in the saline control group.


CONCLUSIONS
The inhibition of iNOS during endotoxaemia by its specific blocker aminoguanidine attenuates the incidence of bacterial translocation in mice. These results may be exploited clinically for the prophylaxis and treatment of septic states.
Kavuklu
B
B
Department of General Surgery, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Agalar
C
C
Guc
M O
MO
Sayek
I
I
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D019446:Endotoxemia / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000302:isolation & purification; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D011513:Proteus mirabilis / Q000302:isolation & purification
D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine