Curcumin modulates leukocyte and platelet adhesion in murine sepsis.
OBJECTIVE
Circulating cell-endothelial cell interaction in sepsis is a rate-determining factor in organ dysfunction, and interventions targeting this process have a potential therapeutic value. In this project, we examined whether curcumin, an active ingredient of turmeric and an anti-inflammatory agent, could disrupt interactions between circulating blood cells and endothelium and improve survival in a murine model of sepsis.


METHODS
Mice were subjected to cecal ligation and puncture (CLP) to induce sepsis vs. sham surgery. We studied leukocyte and platelet adhesion in cerebral microcirculation using intravital fluorescent video microscopy technique, blood-brain barrier (BBB) dysfunction using Evans Blue (EB) leakage method, P-selectin expression using dual radiolabeling technique, and survival in mice subjected to Sham, CLP, and CLP with curcumin pre-treatment (CLP + curcumin).


RESULTS
Curcumin significantly attenuated leukocyte and platelet adhesion in cerebral microcirculation, EB leakage in the brain tissue, and improved survival in mice with CLP. P-selectin expression in mice with CLP + curcumin was significantly attenuated compared with CLP in various microcirculatory beds, including brain. Reduction in platelet adhesion was predominantly via modulation of endothelium by curcumin.


CONCLUSIONS
Curcumin pre-treatment modulates leukocyte and platelet adhesion and BBB dysfunction in mice with CLP via P-selectin expression and improves survival in mice with CLP.
Vachharajani
Vidula
V
Department of Anesthesiology/Section for Critical Care, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. vvachhar@wfubmc.edu
Wang
Si-Wei
SW
Mishra
Nilamadhab
N
El Gazzar
Mohamed
M
Yoza
Barbara
B
McCall
Charles
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects*; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019007:P-Selectin; D003474:Curcumin