Matrix Metalloproteinase-8 Augments Bacterial Clearance in a Juvenile sepsis Model

ABSTRACTObjectivesThe stimulation of the immune response to prevent the progression of the infection may be an adjuvant to antimicrobial treatment. Previously, we showed that preemptive treatment with lysophosphatidylcholine (LPC) in combination with colistin improved the therapeutic efficacy of colistin against MDR Acinetobacter baumannii. In this study, we aimed to evaluate the efficacy of direct treatment with LPC in combination with colistin in murine experimental models of severe infections by A. baumannii.MethodsWe used A. baumannii strain Ab9, which is susceptible to colistin and most of the antibiotics used in clinical settings, and A. baumannii strain Ab186, which is susceptible to colistin but presents a MDR pattern. The therapeutic efficacies of one and two doses of LPC (25 mg/kg/d) and colistin (20 mg/kg/8h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models.ResultsOne and two doses of LPC in combination with colistin and colistin monotherapy enhanced bacterial clearance of Ab9 and Ab186 from spleen, lungs and blood and reduced mortality rates compared with those of the non-treated mice group in both experimental models (P<0.05). Moreover, one and two doses of LPC reduced the bacterial concentration in tissues and blood in both models, and increased mice survival in peritoneal sepsis model for both strains compared with those of colistin monotherapy group.ConclusionsLPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the infection by MDR A. baumannii.

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Mesenchymal stem cells preconditioned by staphylococcal enterotoxin B enhance survival and bacterial clearance in murine sepsis model

Cytotherapy ◽

10.1016/j.jcyt.2018.11.002 ◽

2019 ◽

Vol 21 (1) ◽

pp. 41-53 ◽

Cited By ~ 5

Author(s):

PARDIS SAEEDI ◽

RAHELEH HALABIAN ◽

ABBAS ALI IMANI FOOLADI

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Staphylococcal Enterotoxin ◽

Staphylococcal Enterotoxin B ◽

Bacterial Clearance ◽

Sepsis Model ◽

Enterotoxin B

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β-Lapachone Increases Survival of Septic Mice by Regulating Inflammatory and Oxidative Response

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8820651 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Ana L. de B. Oliveira ◽

Kely C. Navegantes-Lima ◽

Valter V. S. Monteiro ◽

Lucas B. G. Quadros ◽

Juliana P. de Oliveira ◽

...

Keyword(s):

Antioxidant Defense ◽

Cecal Ligation ◽

Protective Effects ◽

Bacterial Clearance ◽

Sepsis Mortality ◽

Sepsis Model ◽

Oxidative Response ◽

Total Antioxidant ◽

Therapeutic Protocols ◽

Defense Function

Sepsis is characterized by a dysregulated immune response to infection characterized by an early hyperinflammatory and oxidative response followed by a subsequent immunosuppression phase. Although there have been some advances in the treatment of sepsis, mortality rates remain high, urging for the search of new therapies. β-Lapachone (β-Lap) is a natural compound obtained from Tabebuia avellanedae Lorentz ex Griseb. with several pharmacological properties including bactericidal, anti-inflammatory, and antioxidant activity. Thus, the aim of this study was to evaluate the effects of β-Lap in a mouse sepsis model. To this, we tested two therapeutic protocols in mice submitted to cecal ligation and puncture- (CLP-) induced sepsis. First, we found that in pretreated animals, β-Lap reduced the systemic inflammatory response and improved bacterial clearance and mouse survival. Moreover, β-Lap also decreased lipid peroxidation and increased the total antioxidant capacity in the serum and peritoneal cavity of septic animals. In the model of severe sepsis, the posttreatment with β-Lap was able to increase the survival of animals and maintain the antioxidant defense function. In conclusion, the β-Lap was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects.

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