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

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 (R). Material and methods: Ninety Wistar rats were submitted to different treatments, and after 12 h and 24 h 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 (R), was compared with a COX2 inhibitor, Celecoxib (R). Methods: Zymosan A (R) 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 (R) given intraperitoneally (SHAM); Group I (control), with Zymosan A (R) (0.6 g/kg) intraperitoneally; Group II (Molsidomine), with Molsidomine (R) (4 mg/kg) through the penis dorsal vein, 30 min prior to administration of the Zy (R) (0.6 g/kg); Group III (Celecoxib), with Celecoxib (R) (400 mg/kg) orally through a stomach tube, 6 h prior to administration of the Zy (0.6 g/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 (R) 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. (C) 2016 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.