Inhibitory effect of dimethyl sulfoxide on nuclear factor-kappa B activation and intercellular adhesion molecule 1 gene expression in septic rats.
Antioxidants are potent radical scavengers that protect against endotoxemia and septic shock in animal models. Using a rat model of peritonitis sepsis induced by cecal incision we studied the effect of the free radical scavenger dimethyl sulfoxide (DMSO) on hepatic nuclear factor kappa B (NF-kappa B) activation, hepatic intercellular adhesion molecule 1 (ICAM-1) gene expression, serum tumor necrosis factor alpha (TNF) formation, and serum glucose concentration. Five groups of rats (N = 5) were treated as follows: (1) untreated control (Untreated), (2) sham operated with laparotomies (Sham), (3) pretreated with 6 ml/kg DMSO followed by sham operation (DMSO/Sham), (4) cecal incision (Sepsis), and (5) pretreated with DMSO followed by cecal incision (DMSO/Sepsis). In the DMSO/Sham group, DMSO did not affect NF-kappa B activation, ICAM-1 gene expression, and TNF formation. At 3 h postcecal incision, DMSO inhibited sepsis-induced hepatic NF-kappa B activation and hepatic ICAM-1 gene expression to control levels and suppressed serum TNF by 75%. In the late (6 h) septic phase, DMSO inhibited NF-kappa B activation (32%), ICAM-1 gene expression (27%), and TNF formation (71%). These findings suggest that the protective mechanism of antioxidants in septic rats may be partly due to the inhibition of NF-kappa B activation and NF-kappa B-mediated events.
Chang
C K
CK
Department of Surgery, Finch University of Health Sciences/Chicago Medical School at Mount Sinai Hospital Medical Center, Chicago, Illinois, 60608, USA.
Llanes
S
S
Schumer
W
W
D000818:Animals; D002432:Cecum / Q000601:surgery; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007239:Infections / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007813:Laparotomy; D008099:Liver / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016166:Free Radical Scavengers; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D004121:Dimethyl Sulfoxide