The effect of methylprednisolone on treatment in rats with induced sepsis

Çeti̇nkaya, Rıza Aytaç; Görenek, Levent; Çoşkun, Ömer; Eyigün, Can Polat; Şenses, Zeynep; İde, Tayfun; Kılıç, Selim

doi:10.1007/s10238-008-0016-y

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…In addition, animal studies have repeatedly demonstrated that exogenous corticosteroids can impair host neutrophil-mediated bacterial clearance mechanisms [7–9], which might explain the excess of positive blood cultures we observed in DOC + DEX-treated animals. More specific to our own study, corticosteroid therapy has been shown to decrease bacterial clearance from the lung in murine models [8], and is most efficacious when administered with appropriate antibiotic therapy [26–28]. These data suggest that adequately dosed and appropriately selected antibiotic therapy is essential whenever corticosteroids are used in septic shock.…”

Section: Discussionmentioning

confidence: 94%

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia

et al. 2012

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Purpose The effects of stress-dose corticosteroid therapy were studied in a staphylococcal pneumonia model of septic shock. Methods Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist and dexamethasone (DEX), a glucocorticoid agonist, or placebo for 96 hours. Oxacillin (30 mg/kg q8h) was started 4 hours after infection onset. Bacterial dose was titrated to achieve 80–90% lethality (n=20) using an adaptive design; additional animals (n=18) were investigated using the highest bacterial dose. Results Initial analysis of all animals (n=38) demonstrated that effects of DOC+DEX were significantly altered by bacterial dose (p=0.04). Dividing the animals into high- and low-bacterial dose groups, treatment effects of DOC+DEX were different for survival (p=0.05), shock reversal (p=0.02), IL-6 levels (p=0.02), and temperature (p=0.01). DOC+DEX significantly improved the above parameters (all, p≤0.03) and lung injury scores (p=0.02) after high-dose bacterial challenges, but not after lower challenges (all, p=ns). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC+DEX increased the frequency of persistent staphylococcal bacteremia [OR 3.09 (1.05–9.11); p=0.04]. Conclusions Stress-dose corticosteroids were only beneficial in sepsis with high risk for death and may interfere with host mechanisms of bacterial clearance.

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Section: Discussionmentioning

confidence: 94%

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia

et al. 2012

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“…However, it suffers from such limitations as the high variability among researchers ( 18 ) and the difficulty in making comparisons among animals with different cecum shapes and sizes ( 4 ). Another known model of sepsis using fecal suspensions has been reported in mice ( 4 ), rats ( 11 ), and sheep ( 12 , 13 ). However, its position as a sepsis model is not well established because their preparation methods are not clearly described ( 11 ) or are complicated ( 4 , 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Another known model of sepsis using fecal suspensions has been reported in mice ( 4 ), rats ( 11 ), and sheep ( 12 , 13 ). However, its position as a sepsis model is not well established because their preparation methods are not clearly described ( 11 ) or are complicated ( 4 , 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Protocol for a Sepsis Model Utilizing Fecal Suspension in Mice: Fecal Suspension Intraperitoneal Injection Model

et al. 2022

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BackgroundVarious animal models of sepsis have been developed to optimize sepsis treatment. However, therapeutic agents that were successful in animal models were rarely effective in human clinical trials. The cecal ligation and puncture (CLP) model is currently the gold standard for sepsis studies. However, its limitations include the high variability among researchers and the difficulty in comparing animals with different cecum shapes and sizes. In this study, we established a protocol for the creation of a simple and accessible sepsis rodent model using fecal suspensions that minimized differences in technical effects among researchers and individual differences in animals.MethodsA mouse model of sepsis using fecal suspension intraperitoneal injection (FSI) was created using fresh stool excreted within 24 h. The collected fresh stool was dissolved in saline solution and filtered. The obtained fecal suspension was injected intraperitoneally into the mice. Moreover, fecal suspensions with different concentrations were prepared, and the survival rates were compared among the fecal suspensions for each concentration. To assess the validity of the FSI as a sepsis model, CLP and FSI with similar mortality rates were compared pathologically, physiologically, immunologically, and bacteriologically. Histopathological comparison was evaluated by hematoxylin-eosin and Gram staining of the parenchymal organs. Physiological evaluation was performed by comparing the respiratory rate, body temperature, and blood gas analysis results. Immunological assessment was performed using multiplex analysis. Bacteriological comparisons were performed by culturing ascites fluid.ResultsThe FSI model increased mortality in proportion to the fecal suspension concentration. The mortality rate was reduced with antibiotic administration. In various comparative experiments conducted using the FSI and CLP models, both models showed findings consistent with sepsis. Furthermore, the FSI model showed less variability among the individuals in each test.ConclusionThis is the first detailed and accurate report of a protocol for creating a sepsis model using fecal suspension. The FSI model is a minimally invasive and accessible sepsis rodent model. Its clinical validity as a sepsis model was proven via histological, physiological, microbiological, and immunological evaluation methods. The FSI model minimizes individual differences between mice and helps to conduct accurate studies after the onset of sepsis.

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Potentiation of pro-inflammatory cytokine suppression and survival by microencapsulated dexamethasone in the treatment of experimental sepsis

Uddin

Siddiq

Oettinger

et al. 2011

Journal of Drug Targeting

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Cytokine inhibiting drugs are much more effective when delivered intracellularly to phagocytic cells in the microencapsulated form. Dexamethasone is a powerful inhibitor of TNF-α cytokine through inhibition of NF-κB which is a gene regulator of multiple pro-inflammatory cytokines. We have determined the effect of microencapsulated dexamethasone in pro-inflammatory cytokine release both in in vitro using whole blood model, and in vivo using peritonitis model of septic shock. Microspheres of 1-4 μm mean size were prepared by using albumin polymer matrix in a one-step spray drying method. Microencapsulated form of dexamethasone with concentration of 10(-1), 10(-2) and 10(-3) M was compared to an equivalent concentration of solution form of dexamethasone in the in vitro whole blood model. The results show microencapsulated dexamethasone inhibited tumor necrosis factor-alpha (TNF-α) and interleukin-beta (IL-1β) significantly in comparison with the solution form of dexamethasone. The in vivo peritonitis model also demonstrated significant inhibition of TNF-α and IL-1β cytokines in microencapsulated form in comparison with solution form of dexamethasone. In the in vivo study, the animal survival rate after 5 days was 90%, dexamethasone in solution with gentamicin was 40% and gentamicin alone was 30%. This study demonstrates significantly improved inhibition of TNF-α and IL-1β both in vivo and in vitro when dexamethasone was used in microencapsulated form.

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The effect of methylprednisolone on treatment in rats with induced sepsis

Cited by 3 publications

References 35 publications

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia

Protocol for a Sepsis Model Utilizing Fecal Suspension in Mice: Fecal Suspension Intraperitoneal Injection Model

Potentiation of pro-inflammatory cytokine suppression and survival by microencapsulated dexamethasone in the treatment of experimental sepsis

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