Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties

BACKGROUND: Membranous glomerulonephritis (MGN) is a nephrotic syndrome which shows the symptoms of heavy proteinuria and immune complex deposition in glomerular sub-epithelial space and finally leads to chronic kidney disease. Isoliquiritin (ILQ) is a flavonoid with a wide range of pharmacological properties, including antioxidant and anti-inflammatory activity. The present study was undertaken to investigate the possible mechanisms by which ILQ ameliorates cationic bovine serum albumin (C-BSA) induced MGN in rat model. METHODS: The MGN condition was confirmed by the 24 hr proteinuria and ILQ (10 mg/kg/bw/day) or TPCA-1 (10 mg/kg/bw/day; IKKβ inhibitor) was administered to successfully induce rats for 4 weeks. RESULTS: The present study revealed that MGN rats treated with ILQ showed significantly ameliorated kidney dysfunction and histopathological changes in kidneys. ILQ treated MGN rats alleviated the oxidative stress and were presented with increased anti-oxidative status in kidneys. Furthermore, ILQ treatment to MGN rats showed anti-oxidative effects through the prominent stimulation of Nrf2 signaling pathway and inhibition of Keap1, which consequently increases the Nrf2 nuclear translocation and thereby induces expression of NQO1 and HO-1. In addition, ILQ-treated MGN rats demonstrated anti-inflammatory effects by inhibiting NF-κB signaling pathway through decreased mRNA and protein expressions of NF-κB p65, IKKβ, COX-2, iNOS, p38-MAPK, p-p38-MAPK, TNF-α, IL-1β, IL-8, ICAM-1, E-selectin and VCAM-1 and reduced the nuclear translocation of NF-κB p65. CONCLUSION: The protective effect of ILQ on MGN can be explained by its anti-oxidative and anti-inflammatory activities, which in turn due to the activation of Nrf2 and downregulation of NF-κB pathway.