Inhibitory Effect of Dimethyl Sulfoxide on Nuclear Factor-κB Activation and Intercellular Adhesion Molecule 1 Gene Expression in Septic Rats

Abstract 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 κB (NF-κB) activation, hepatic intercellular adhesion molecule 1 (ICAM-1) gene expression, serum tumor necrosis factor α (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-κB activation, ICAM-1 gene expression, and TNF formation. At 3 h postcecal incision, DMSO inhibited sepsis-induced hepatic NF-κB 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-κB 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-κB activation and NF-κB-mediated events.