Ethanol Consumption Promotes Tnf-Α Signaling Pathway in Rat Kidney: Rescue Effect of Curcumin

Tumor necrosis factor-α (tnfα) has several biological effects, including cell death, cell apoptosis and proliferation, and differentiation, as well as immune modulation. we characterized the alteration in tnf-α and the key receptors and molecular mediators related to tnf-α signaling pathway in the kidney after exposure to ethanol alone or in combination with curcumin (cr). accordingly, 24 male wistar rats in 3 groups of control, ethanol, and cr-treated - ethanolic groups were treated for six weeks. the ethanol group showed a significant elevation in tnf-α, nuclear factor-κb (nf-κb), and endothelin 1 (et1) than the control group. tnf-α receptor 1 (tnfr1), tnf-α receptor 2 (tnfr2) and vascular endothelial growth factor receptor 2 (vegfr2) were found with a significant down-regulation, and of tnf-receptor-associated factor 2 (traf2) and receptor-interacting protein-1 (rip-1), and activator protein-1 (ap-1) were found with an up-regulation in the ethanol group than the control group. cr and ethanol decreased the gene expression of traf-2, rip-1 and ap-1, as well as increased the gene expression of tnfr1. cr administration restored the increased levels of tnf-α, nf-κb and endothelin to these levels in the control group. therefore, ethanol-related kidney injury addressed by our previous studies and others may in part be associated with the tnf-α signaling pathway, and such impacts can be rescued by cr as an antioxidant and anti-inflammatory compound. introduction chronic ethanol exposure induces structural damages of the kidney[1], however, l the accurate molecular mechanisms of ethanol to damage to kidney is not clear. recently, ethanol has been shown to cause tissue damage via inflammatory stress [2, 3]. tumor necrosis factor-α (tnf-α) as a proinflammatory cytokine is mainly generated by immune cells, like macrophages and can stimulate the inflammatory mediators, like eicosanoids, interleukin-1 (il-1), and platelet-activating factor [4]. tnf- α appears free in the plasma or is bound to circulating tnf receptor 1 (tnfr1) and tnf receptor 2 (tnfr2). it can attach to the type 1 and 2 transmembrane receptors originating from separate gene products[5]. during kidney inflammation, the *corresponding