Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties
Authors Liu Y, Xu X, Xu R, Zhang S
Received 23 April 2019
Accepted for publication 8 August 2019
Published 30 October 2019 Volume 2019:13 Pages 3735—3751
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Tin Wui Wong
Yingying Liu,1,* Xiaohua Xu,1,* Ruisi Xu,2 Siqi Zhang1
1Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 2Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Siqi Zhang
Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China
Tel +86 183 3112 5890
Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China
Tel +86 187 3220 0909
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.
Keywords: isoliquiritin, membranous glomerulonephritis, oxidative stress, inflammation
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