Ethanol Consumption Promotes TNF-α Signaling Pathway in Rat Kidney: Rescue Effect of Curcumin

Abstract

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.