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Effect of fangchinoline in murine models of multiple organ dysfunction syndrome and septic shock
M Hristova1, M Yordanov, N Ivanovska
1Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26 G. Bonchev Str., 1113 Sofia, Bulgaria.
Objective And Design:
To study the effect of the alkaloid fangchinoline on zymosan-induced multiple organ dysfunction syndrome (MODS) and Escherichia coli (E. coli)-induced septic shock.
Material:
Male ICR mice were used. Macrophages were isolated from peritoneal cavity for in vitro study.
Treatment:
Fangchinoline was administered i.p. at a dose of 1 or 5 mg/kg into the mice.
Methods:
MODS was induced by intraperitoneal (i.p.) injection of zymosan at a dose 1.0 or 0.8/g b.w. E. coli-induced septic shock was provoked by i.p. inoculation of 5 x 10(8) bacterial cells into mice. TNF-alpha in serum and supernatants from peritoneal macrophages was detected by the use of L-929 cell cytotoxic assay. Alternative pathway (AP) complement activity was determined by hemolytic assay.
Results:
Fangchinoline increased the survival rate in lethal MODS and septic shock. The alkaloid prevented the loss of body weight and liver enlargement in MODS and suppressed serum tumor necrosis factor-alpha (TNF-alpha) accumulation in MODS and septic shock.
Conclusions:
The result suggest that fangchinoline due mainly to its ability to downregulate TNF-alpha production might have protective effect in murine models of zymosan-induced MODS and E. coli-induced septic shock.
Insights
Fangchinoline, an alkaloid, improved survival rates in mouse models of multiple organ dysfunction syndrome (MODS) and septic shock. It reduced inflammation by lowering tumor necrosis factor-alpha (TNF-alpha) levels.
Area of Science:
- Pharmacology
- Immunology
- Toxicology
Background:
- Multiple organ dysfunction syndrome (MODS) and septic shock are life-threatening conditions.
- Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of MODS and septic shock.
- Fangchinoline is an alkaloid with potential anti-inflammatory properties.
Purpose of the Study:
- To investigate the therapeutic effects of fangchinoline on zymosan-induced MODS and Escherichia coli (E. coli)-induced septic shock in mice.
- To evaluate the impact of fangchinoline on survival rates, body weight, liver enlargement, and TNF-alpha levels in these models.
Main Methods:
- Male ICR mice were used to establish models of MODS and septic shock.
- Fangchinoline was administered intraperitoneally at doses of 1 or 5 mg/kg.
- Serum TNF-alpha levels were measured using a cytotoxic assay, and alternative pathway (AP) complement activity was assessed.
Main Results:
- Fangchinoline significantly increased survival rates in both MODS and septic shock models.
- The alkaloid mitigated body weight loss and liver enlargement associated with MODS.
- Fangchinoline suppressed the accumulation of serum TNF-alpha in both conditions.
Conclusions:
- Fangchinoline demonstrates protective effects in murine models of MODS and septic shock.
- The therapeutic benefit of fangchinoline is primarily attributed to its ability to downregulate TNF-alpha production.
- These findings suggest fangchinoline as a potential therapeutic agent for sepsis-related organ dysfunction.