Impacto de Lactobacillus rhamnosus CRL1505 sobre los mecanismos hemostáticos alterados durante la inmunosupresión experimental inducida por la ciclofosfamida

Abstract

Different drugs used during cancer treatments can affect the hemostatic mechanisms. Previously, we demonstrated that lactic acid bacteria modulate effectively coagulation activation during respiratory infections. The aim of this work was to evaluate whether viable or non-viable Lactobacillus rhamnosus CRL1505 (Lr1505V or Lr1505NV) were able to modulate alterations on hemostatic mechanisms induced by cyclophosphamide (Cy), an antineoplastic drug used in several types of cancer.Adult Swiss-mice were orally treated with LrV or LrNV (108 CFU/d/mouse) during 5 consecutive days. On day 6, lactobacilli-treated and untreated control mice received one intraperitoneal dose of Cy (150 mg/kg). Cy only decreased prothrombin activity and platelet count, but the platelet count reached normal values at the end of the experiment. Considering that Cy did not induce significant alterations, we decided to study the effect of LrV or LrNV in an experimental pneumosepsis model in immunosuppressed host by Cy. At day 3 post Cy administration, the immunosuppressed mice were nasally infected with Streptococcus pneumoniae 6B (107 CFU/ml). Cy-treated mice showed increased susceptibility to infection and alterations in the immune-coagulative response. However, preventive administration of L. rhamnosus significantly reduced microbial counts in lung and blood, regulated TNF-α/IL-10 ratio in serum, and modulated hemostatic parameters with increase in prothrombin activity, normalization of platelet counts, and temporal increase of fibrinogen that act as acute phase protein. The results suggest that L. rhamnosus modulate immune-coagulative response during an early S. pneumoniae-infection in Cy-immunosuppressed mice. It would be necessary a later evaluation of the hemostatic parameters during the infection, and to study some specific marker of coagulation activation and/or fibrinolysis, as well as endothelial activation markers.Fil: Gramajo López, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentin