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.
Highlights
Finasteride is a steroidal inhibitor of 5α-reductase type 2 (5α-red2), which prevents irreversible reduction of T into DHT [1,2]
We observed that long-lasting (3–4 months) finasteride treatment of adult male rats caused a decline in sex hormone levels, firstly with DHT, T and E2, the level of estradiol did not change statistically significantly
The website of Archived Drug Label [50] states that, after the finasteride administration, “mean circulating levels of testosterone and estradiol were increased by approximately 15%,” which is consistent with the research [51,52]
Summary
Finasteride is a steroidal inhibitor of 5α-reductase type 2 (5α-red2), which prevents irreversible reduction of T (testosterone) into DHT (dihydrotestosterone) [1,2] It is commonly used in the treatment of prostate cancer, benign prostatic hyperplasia (BPH), and androgenic alopecia (AGA) [3,4,5]. The influence of sex hormones on the kidney is associated with the close connection between urinary and reproductive systems [9]. For this reason, the proper development and correct physiology of the urogenital (UG) system significantly depends on androgen-estrogen homeostasis [10,11]
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