Effect of fangchinoline in murine models of multiple organ dysfunction syndrome and septic shock.
OBJECTIVE
To study the effect of the alkaloid fangchinoline on zymosan-induced multiple organ dysfunction syndrome (MODS) and Escherichia coli (E. coli)-induced septic shock.


METHODS
Male ICR mice were used. Macrophages were isolated from peritoneal cavity for in vitro study.


METHODS
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.
Hristova
M
M
Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26 G. Bonchev Str., 1113 Sofia, Bulgaria.
Yordanov
M
M
Ivanovska
N
N
D000469:Alkaline Phosphatase / Q000097:blood; D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D044182:Benzylisoquinolines; D003165:Complement System Proteins / Q000096:biosynthesis; D004927:Escherichia coli Infections / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015054:Zymosan
D000470:Alkaloids; D044182:Benzylisoquinolines; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins; D015054:Zymosan; C060802:fangchinoline; D000469:Alkaline Phosphatase