Comparative study of bacterial translocation control with nitric oxide donors and COX2 inhibitor

Abstract

Objective and design: To evaluate the beneficial effects of exogenous NO and an inhibitor of the COX2, and their action levels in a model of SIRS/bacterial translocation (BT) induced by Zymosan A(®).

Material and methods: Ninety Wistar rats were submitted to different treatments, and after 12h and 24h they were anaesthetized in order to collect blood, mesenteric lymph nodes, and kidney for subsequent biochemical analyses and microbiological examinations.

Treatments: A nitric oxide donor, Molsidomine(®), was compared with a COX2 inhibitor, Celecoxib(®).

Methods: Zymosan A(®) was administered to Wistar rats. The animals were divided into 6 groups: one group for survival study, Group (1) No manipulation (BASAL); Group (2) vehicle of Zymosan A(®) given intraperitoneally (SHAM); Group I (control), with Zymosan A(®) (0.6g/kg) intraperitoneally; Group II (Molsidomine), with Molsidomine(®) (4mg/kg) through the penis dorsal vein, 30min prior to administration of the Zy(®) (0.6g/kg); Group III (Celecoxib), with Celecoxib(®) (400mg/kg) orally through a stomach tube, 6h prior to administration of the Zy (0.6g/kg).

Determinations: The parameters survival, bacterial translocation, renal function, neutrophil accumulation, oxygen free radicals (OFR), detoxifying enzymes, and cytokines were measured at different times after Zymosan administration.

Results: The model established induced a mortality rate of 100% and generated BT and systemic inflammatory response syndrome (SIRS) in all samples. It also significantly increased all variables, with p<.001 for MPO and all pro-inflammatory cytokines, and p<.01 for all OFR. Treatment with Molsidomine reduced mortality to 0%, decreased BT, MPO, pro-inflammatory cytokines and OFR (p<.001) significantly and increased IL-10 and IL-6 production. Moreover, the Celecoxib(®) showed a lower capacity for SIRS regulation.

Conclusions: The exogenous administration of NO prevented BT and controlled SIRS. Therefore these results suggest that Molsidomine could be used as a therapeutic strategy to protect against BT.

Keywords: Bacterial translocation; Multi-organ dysfunction syndrome (MODS); Nitric oxide; Systemic inflammatory response syndrome (SIRS); Síndrome de Disfunción Multiorgánica (SDMO); Síndrome de Respuesta Inflamatoria Sistémica (SRIS); Translocación bacteriana; Óxido nítrico.