Bacterial Translocation Is Inhibited in Inducible Nitric Oxide Synthase Knockout Mice After Endotoxin Challenge but Not in a Model of Bacterial Overgrowth

Shiro Mishima, MD; DaZhong Xu, MD; Qi Lu, MD; Edwin A. Deitch, MD
Arch Surg. 1997;132(11):1190-1195. doi:10.1001/archsurg.1997.01430350040007.
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Background:  Studies have shown that nitric oxide (NO) and NO synthase (NOS) inhibitors injure and protect organs after endotoxin (lipopolysaccharide [LPS]) challenge.

Objective:  To test the hypothesis that LPS-induced gut injury and bacterial translocation (BT) are mediated through activation of inducible NOS (iNOS).

Design:  A randomized, controlled study using genetically altered, iNOS gene knockout mice.

Setting:  University research laboratory.

Methods:  Forty-five wild-type (iNOS+/+) or homozygous mutant (iNOS−/−) mice weighing 25 to 35 g were challenged with Escherichia coli LPS or saline (10 mg/kg) intraperitoneally (n=8/group). In a second set of experiments, a bacterial overgrowth model of BT (E coli monoassociation) was tested (n=6-7/group). The mesenteric lymph nodes and cecums were cultured, and liver, ileal, and blood nitrite and nitrate levels measured 24 hours after LPS or E coli monoassociation.

Results:  After LPS challenge, 87.5% of the iNOS+/+ mice but 0% of the iNOS−/− mice had BT to their mesenteric lymph nodes (P<.01; χ2 analysis). Nitrite and nitrate levels of the liver, ileum, and blood were higher in the iNOS+/+ mice (P<.05). In the E coli overgrowth model, BT to mesenteric lymph nodes occurred in 100% of iNOS−/− and iNOS+/+ mice.

Conclusions:  In this limited study, LPS-induced BT did not occur in iNOS-deficient mice, suggesting that LPS induction of increased iNOS activity is necessary for LPS-induced BT to occur. In contrast, iNOS activation does not seem to be necessary in a bacterial overgrowth model of BT.Arch Surg. 1997;132:1190-1195


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