Finasteride-Induced Inhibition of 5?-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study

Mirza Saim Baig, Agnieszka Kolasa-Wołosiuk, Anna Pilutin, Krzysztof Safranow, Irena Baranowska-Bosiacka, Joanna Kabat-Koperska and Barbara Wiszniewska
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Mirza Saim Baig: Department of Histology and Embryology, Pomeranian Medical University, Powst. Wlkp. 72, 70-111 Szczecin, Poland
Agnieszka Kolasa-Wołosiuk: Department of Histology and Embryology, Pomeranian Medical University, Powst. Wlkp. 72, 70-111 Szczecin, Poland
Anna Pilutin: Department of Histology and Embryology, Pomeranian Medical University, Powst. Wlkp. 72, 70-111 Szczecin, Poland
Krzysztof Safranow: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland
Irena Baranowska-Bosiacka: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland
Joanna Kabat-Koperska: Department of Nephrology, Transplantology and Internal Medicine Pomeranian Medical University, Powst. Wlkp. 72, 70-111 Szczecin, Poland
Barbara Wiszniewska: Department of Histology and Embryology, Pomeranian Medical University, Powst. Wlkp. 72, 70-111 Szczecin, Poland

IJERPH, 2019, vol. 16, issue 10, 1-21

Abstract: In the pharmacological treatment of prostate cancer, benign prostatic hyperplasia and androgenetic alopecia finasteride is commonly used. This drug inhibits 5α-reductase type 2, which is why finasteride affects androgen homeostasis, since testosterone (T) cannot be reduced to dihydrotestosterone (DHT). As studies on sex-related renal injuries suggest a high probability of androgen-induced renal dysfunction, the aim of this study was to determine the potential harmful effects of finasteride on the kidneys of rats. The study was performed on sexually mature male Wistar rats given finasteride. Histological sections of the kidneys were used for immunohistochemical visualization of the androgen receptor (AR), junctional proteins (occluding (Occ); E-cad, N-cad, E-/N-cadherin; β-cat, β-catenin; connexin 43 (Cx43)), proliferating cell nuclear antigen (PCNA), IL-6, and lymphocyte markers (CD3 for T cell, CD19 for B cell). The TUNEL method was used for cell apoptosis identification, and picro sirius red staining was used to assess collagen fibers thickness. The levels of T, DHT and estradiol (E2) were determined in blood serum. It was shown that finasteride treatment affected steroid hormone homeostasis, altered the expression of AR and intracellular junction proteins, changed the ratio between cell apoptosis and proliferation, and caused lymphocyte infiltration and an increase of IL-6. The thickening of collagen fibers was observed as tubular fibrosis and glomerulosclerosis. Summarizing, finasteride-induced hormonal imbalance impaired the morphology (i.e., dysplastic glomeruli, swollen proximal convoluted tubules) and physiology (changed level of detected proteins/markers expression) of the kidneys. Therefore, it is suggested that patients with renal dysfunction or following renal transplantation, with androgen or antiandrogen supplementation, should be under special control and covered by extended diagnostics, because the adverse negative effect of DHT deficiency on the progression of kidney disease cannot be ignored.

Keywords: kidney; finasteride; androgen receptor; apoptosis; proliferation; junction proteins; IL-6; lymphocytes infiltration; renal fibrosis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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