MP34-05
            N
            -METHYL-4-ISOLEUCINE CYCLOSPORINE, AN INHIBITOR OF MITOCHONDRIAL CYCLOPHILIN D ACTIVATION, PREVENTS KIDNEY STONE FORMATION BY ALLEVIATING OXIDATIVE STRESS IN RENAL TUBULAR CELLS

Abstract Objectives Hyaluronic acid (HA), a large non-sulfated glycosaminoglycan, is one of the major components of extracellular matrix (ECM) in connective tissues and other organs. Currently, it is widely used as a dietary supplement, especially for treatment or prevention of aging-related disorders. On the other hand, HA has been reported with an increased risk of kidney stone disease, particularly calcium oxalate (CaOx) type, but with unclear mechanisms. We therefore performed systematic analyses for its modulatory effects on CaOx monohydrate (COM) crystal at various steps of kidney stone formation processes. Methods HA at 1, 10, 100, 1000 and 10,000 ng/ml was tested in various assays for COM crystallization, crystal growth, aggregation, crystal-cell adhesion and invasion through ECM. Results COM crystallization and crystal aggregation were not affected by HA at all concentrations. However, HA significantly promoted COM crystal growth and adhesion onto renal tubular cells in a dose-dependent manner. Interestingly, COM crystal invasion through the ECM was dramatically enhanced by HA even at very low concentration (such as 1 ng/ml). Conclusions Our findings provide evidence for promoting effects of HA on COM crystal growth, adhesion on renal tubular cell surface and invasion through the ECM, all of which are the important steps for kidney stone formation. Funding Sources TRF-IRN grant.

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MicroRNA-204 attenuates oxidative stress damage of renal tubular epithelial cells in calcium oxalate kidney-stone formation via MUC4-mediated ERK signaling pathway

Urolithiasis ◽

10.1007/s00240-021-01286-y ◽

2021 ◽

Author(s):

Zhijuan Xie ◽

Jianying Chen ◽

Zhong Chen

Keyword(s):

Oxidative Stress ◽

Calcium Oxalate ◽

Kidney Stone ◽

Stone Formation ◽

Erk Signaling ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular ◽

Stress Damage ◽

Kidney Stone Formation

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Reduction of Oxidative Stress in Cultured Renal Tubular Cells and Preventive Effects on Renal Stone Formation by the Bioflavonoid Quercetin

The Journal of Urology ◽

10.1016/j.juro.2007.11.039 ◽

2008 ◽

Vol 179 (4) ◽

pp. 1620-1626 ◽

Cited By ~ 30

Author(s):

Hyoung Keun Park ◽

Byong Chang Jeong ◽

Mi-Kyung Sung ◽

Mi-Young Park ◽

Eun Young Choi ◽

...

Keyword(s):

Oxidative Stress ◽

Renal Stone ◽

Stone Formation ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Preventive Effects

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MP24-06 CYCLOPHILIN D PARTICIPATION IN THE PROMOTION OF KIDNEY STONE FORMATION VIA OXIDATIVE STRESS

The Journal of Urology ◽

10.1016/j.juro.2018.02.759 ◽

2018 ◽

Vol 199 (4S) ◽

Author(s):

Yasuhiko Ito ◽

Kazuhiro Niimi ◽

Rei Unno ◽

Yutaro Tanaka ◽

Teruaki Sugino ◽

...

Keyword(s):

Oxidative Stress ◽

Kidney Stone ◽

Stone Formation ◽

Cyclophilin D ◽

Kidney Stone Formation

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Losartan Ameliorates Calcium Oxalate-Induced Elevation of Stone-Related Proteins in Renal Tubular Cells by Inhibiting NADPH Oxidase and Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/1271864 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Baolong Qin ◽

Qing Wang ◽

Yuchao Lu ◽

Cong Li ◽

Henglong Hu ◽

...

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Calcium Oxalate ◽

Stone Formation ◽

Ang Ii ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Related Proteins ◽

And Oxidative Stress

Calcium oxalate (CaOx) is the most common type of urinary stone. Increase of ROS and NADPH oxidase gives rise to inflammation and injury of renal tubular cells, which promotes CaOx stone formation. Recent studies have revealed that the renin-angiotensin system might play a role in kidney crystallization and ROS production. Here, we investigated the involvement of Ang II/AT1R and losartan in CaOx stone formation. NRK-52E cells were incubated with CaOx crystals, and glyoxylic acid-induced hyperoxaluric rats were treated with losartan. Oxidative stress statuses were evaluated by detection of ROS, oxidative products (8-OHdG and MDA), and antioxidant enzymes (SOD and CAT). Expression of NADPH oxidase subunits (Nox2 and Nox4), NF-κB pathway subunits (p50 and p65), and stone-related proteins such as OPN, CD44, and MCP-1 was determined by Western blotting. The results revealed upregulation of Ang II/AT1R by CaOx treatment. CaOx-induced ROS and stone-related protein upregulation were mediated by the Ang II/AT1R signaling pathway. Losartan ameliorated renal tubular cell expression of stone-related proteins and renal crystallization by inhibiting NADPH oxidase and oxidative stress. We conclude that losartan might be a promising preventive and therapeutic candidate for hyperoxaluria nephrolithiasis.

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