Aspirin (NSC 27223)

Aspirin inhibits the activation of NF-kappa B, thus prevents the degradation of the NF-kappa B inhibitor, I kappa B, and therefore NF-kappa B is retained in the cytosol. Aspirin also inhibits NF-kappa B-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells. ^[1] Aspirin and salicylate are mediated in part by their specific inhibition of IKK-beta, thereby preventing activation by NF-kappaB of genes involved in the pathogenesis of the inflammatory response. ^[2] Aspirin is protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. ^[3] Aspirin triggers transcellular biosynthesis of a previously unrecognized class of eicosanoidsduring coincubations of human umbilical vein endothelial cells (HUVEC) and neutrophils [polymorphonuclear leukocytes (PMN)]. Aspirin evokes a unique class of eicosanoids formed by acetylated PGHS-2 and 5-lipoxygenase interactions. ^[4] Aspirin treatment inhibits the phosphorylation of IRS-1 at Ser307 as well as the phosphorylation of JNK, c-Jun, and degradation of IkappaBalpha in 3T3-L1 and Hep G2 cells treated with tumor necrosis factor (TNF)-alpha. Aspirin treatment inhibits phosphorylation of Akt and the mammalian target of rapamycin (but not extracellular regulated kinase or PKCzeta) in response to TNF-alpha. Aspirin rescues insulin-induced glucose uptake in 3T3-L1 adipocytes pretreated with TNF-alpha. ^[5]