Sirtinol attenuates hepatic injury and pro-inflammatory cytokine production following trauma-hemorrhage in male Sprague-Dawley rats.
BACKGROUND
Although studies have demonstrated that sirtinol administration following adverse circulatory conditions is known to be protective, the mechanism by which sirtinol produces the salutary effects remains unknown. We hypothesized that sirtinol administration in male rats following trauma-hemorrhage decreases cytokine production and protects against hepatic injury.


METHODS
Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). A single dose of sirtinol (1 mg/kg of body weight) or vehicle was administered intravenously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase (MPO) activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 levels in the liver and plasma alanine aminotransferase (ALT) concentrations were measured (n=6 Sprague-Dawley rats/group).


RESULTS
Trauma-hemorrhage increased hepatic MPO activity, CINC-1, CINC-3, ICAM-1, and IL-6 levels and plasma ALT concentrations. These parameters were significantly improved in the sirtinol-treated rats subjected to trauma-hemorrhage.


CONCLUSIONS
The salutary effects of sirtinol administration on attenuation of hepatic injury following trauma-hemorrhage are, at least in part, related to reduction of pro-inflammatory mediators.
Liu
F-C
FC
Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Day
Y-J
YJ
Liou
J-T
JT
Lau
Y-T
YT
Yu
H-P
HP
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D006470:Hemorrhage / Q000188:drug therapy* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009284:Naphthols / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism
D001549:Benzamides; D016207:Cytokines; D009284:Naphthols; C439060:sirtinol; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D000410:Alanine Transaminase