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Protective effects of finasteride against testosterone-induced calcium oxalate crystallization and crystal-cell
Kanyarat Sueksakit1, Visith Thongboonkerd2
1Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, 6th Floor-SiMR Building, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand.
Abstract:
Finasteride (a 5α-reductase inhibitor) has been widely used for treatment of several testosterone-related disorders. However, its beneficial role in kidney stone disease had not been previously investigated. This study thus addressed whether finasteride has any protective effects against testosterone-induced calcium oxalate monohydrate (COM) kidney stone formation. Renal tubular cells were treated with testosterone with/without finasteride for 72 h. Western blotting revealed the increased level of α-enolase (a known COM crystal receptor) in whole-cell lysate, apical membrane, and cytosolic fraction of the testosterone-treated cells. Immunofluorescence staining also showed the increased levels of surface and intracellular α-enolase in the testosterone-treated cells. In addition, testosterone significantly increased the number of adherent COM crystals on the cell surface. All of these effects were completely abolished by finasteride treatment. Interestingly, the secreted proteins from testosterone-treated cells significantly increased COM crystallization, but did not affect crystal growth and aggregation. Again, such promoting effect of testosterone on COM crystallization was completely abolished by finasteride. These data indicate that finasteride effectively protects testosterone-induced kidney stone formation by restoring apical surface expression of α-enolase and COM crystal-cell adhesion to their basal levels. Moreover, finasteride can also neutralize the promoting effect of testosterone on COM crystallization.
Insights
Finasteride prevents kidney stone formation by blocking testosterone's effects on cell surfaces and crystal growth. This study reveals finasteride's protective role against testosterone-induced calcium oxalate monohydrate stones.
Area of Science:
- Nephrology
- Endocrinology
- Biochemistry
Background:
- Finasteride is a 5α-reductase inhibitor used for testosterone-related disorders.
- Its role in kidney stone disease was previously uninvestigated.
Purpose of the Study:
- To investigate the protective effects of finasteride against testosterone-induced calcium oxalate monohydrate (COM) kidney stone formation.
- To explore finasteride's impact on α-enolase expression and COM crystal adhesion.
Main Methods:
- Renal tubular cells were treated with testosterone and finasteride.
- Western blotting and immunofluorescence staining assessed α-enolase levels.
- COM crystal adhesion and crystallization were analyzed.
Main Results:
- Testosterone increased α-enolase levels and COM crystal adhesion to renal tubular cells.
- Finasteride treatment abolished these testosterone-induced effects.
- Testosterone-induced promotion of COM crystallization was also reversed by finasteride.
Conclusions:
- Finasteride protects against testosterone-induced kidney stone formation.
- It normalizes α-enolase expression and COM crystal-cell adhesion.
- Finasteride neutralizes testosterone's pro-crystallization effects.
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