The Journal of surgical research
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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). ⋯ 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.
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Nitric oxide (NO), cGMP, and cAMP affect the synthesis, metabolism, and cellular effects each other. We wanted to study how cGMP and cAMP interact to affect the induced synthesis of NO in response to interleukin-1 beta (IL-1 beta) in rat pulmonary artery smooth muscle cells. To further dissect the relative contributions of each cyclic nucleotide, and to detect any possible "crossover" effect of one cyclic nucleotide activating the other protein kinase, we tested how pharmacological inhibition of cGMP-dependent and cAMP-dependent protein kinases (PKG and PKA, respectively) affected responses. ⋯ Both cAMP and cGMP augment cytokine induction of NO synthesis through activation of PKA: cAMP does so directly; cGMP, through a crossover stimulation of PKA.