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Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Protective effect of the novel cyclic peptide ASK0912 on mice with sepsis induced by Acinetobacter baumannii
Chunyang Xie1, Penghe Wang1, Huige Wu1
1Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Background:
Sepsis has become a global health concern owing to its increasing incidence and high mortality rate. In the present study, we investigated a novel drug candidate ASK0912 on its protective effects in mice with Acinetobacter baumannii 20-1-induced sepsis, and studied the related mechanisms.
Material And Methods:
To analyze the protective effect of ASK0912 on septic mice, survival rates, body temperature, organ and blood bacterial loads, white blood cell and platelet counts, organ damage, and cytokine levels were determined.
Results:
ASK0912 remarkably increased the survival rate of mice with sepsis induced by A. baumannii 20-1 at a low dose of 0.6 mg/kg. Rectal temperature measurements showed that ASK0912 treatment prevented the body temperature decrease of septic mice to some extent. Treatment with ASK0912 can notably reduce the organ and blood bacterial loads and alleviate platelet count reduction due to sepsis. ASK0912 attenuated organ damage, including reduced levels of total bile acids, urea, and creatinine, aggregation of inflammatory cells, and mitigation of structural changes in septic mice, as demonstrated by biochemical analysis and hematoxylin & eosin staining. Additionally, multiplex assay showed that abnormally increased cytokine levels (IL-1β, IL-3, IL-5, IL-6, IL-10, IL-13, MCP-1, RANTES, KC, MIP-1α, MIP-1β, and G-CSF) in septic mice decreased after ASK0912 treatment.
Conclusions:
ASK0912 can not only improve the survival rate, hypothermia, lower the bacterial loads in the organs and blood, but also alleviate the pathophysiological manifestations such as intravascular coagulation abnormalities, organ damages, and immune system disorder of sepsis mice induced by A. baumannii 20-1.
Insights
The novel drug candidate ASK0912 significantly improves survival rates in mice with Acinetobacter baumannii sepsis. This sepsis treatment reduces bacterial load, prevents hypothermia, and mitigates organ damage and immune system dysfunction.
Area of Science:
- Microbiology
- Pharmacology
- Immunology
Background:
- Sepsis presents a significant global health challenge due to rising incidence and mortality.
- Acinetobacter baumannii is a common pathogen causing severe sepsis.
- Investigating novel therapeutic agents is crucial for combating sepsis.
Purpose of the Study:
- To evaluate the protective effects of the novel drug candidate ASK0912 against Acinetobacter baumannii-induced sepsis in a mouse model.
- To elucidate the underlying mechanisms of ASK0912's action in sepsis.
Main Methods:
- Survival rates, body temperature, and bacterial loads in organs and blood were assessed.
- Hematological parameters (white blood cell and platelet counts) and organ damage markers were analyzed.
- Cytokine profiles were determined using multiplex assays, and histopathological changes were evaluated via H&E staining.
Main Results:
- ASK0912 significantly increased survival rates in septic mice at a low dose (0.6 mg/kg).
- Treatment with ASK0912 reduced bacterial loads, prevented hypothermia, and improved platelet counts.
- ASK0912 attenuated organ damage, including reduced biochemical markers and inflammatory cell aggregation, and normalized elevated cytokine levels.
Conclusions:
- ASK0912 demonstrates significant therapeutic potential for sepsis treatment.
- The drug improves survival, reduces bacterial burden, and mitigates sepsis-induced organ damage and immune dysregulation.
- ASK0912 offers a promising novel therapeutic strategy for Acinetobacter baumannii sepsis.

