Figure 1.

ONOO⁻ inhibition prevents the failure of neutrophil migration and improves survival rates in septic mice. Mice were subjected to sham, moderate (MSI) or severe (SSI) injury after CLP, as described in the Methods section. (a) Neutrophil migration into the peritoneal cavity was performed 6 h after CLP. Animals were pretreated s.c., with saline or with indicated doses of UA, 1 h before induction of SSI or with indicated doses of FeTPPS, 15 min after SSI. The results are expressed as mean±s.e.m. of 10 animals per group. ^*P<0.001 compared to sham group; ^#P<0.001 compared to MSI group; ^**P<0.05 compared to saline-pretreated mice with SSI (multifactorial ANOVA, followed by Tukey's test). (b) The mice were in sham or MSI groups. The MSI group were pretreated with saline or UA (10 or 100 mg kg⁻¹) 1 h before the surgery. (c) The mice were in sham or SSI groups. The SSI group were pretreated with saline or UA (100 mg kg⁻¹) 1 h before the surgery or treated with UA 6 and 18 h after SSI (100 mg kg⁻¹). Another group of SSI was treated with FeTPPs, 15 min after surgery (5 mg kg⁻¹). The survival rates of animals were determined every 8 h until 120 h after CLP. Results are expressed as % survival (n=6 animals per group). ^*P<0.01 compared to MSI or SSI group (Mantel–Cox log-rank test). ANOVA, analysis of variance; CLP, cecal ligation and puncture; FeTPPS, 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinato iron(III); MSI, moderate septic injury; ONOO⁻, peroxynitrite; s.c., subcutaneously; SSI, severe septic injury; UA, uric acid.