Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Hormone Assays
2.3. Immunohistochemistry (IHC)
2.4. Collagen Fiber Visualization and Validation
2.5. Apoptosis In Situ Detection
Validation of TUNEL-Positive (Apoptotic Cell) and PCNA-Positive (Proliferating Cell)
2.6. Statistical Analysis
3. Results
3.1. Sex Hormone Levels
3.2. Androgen Receptor Expression
3.3. Junctional Protein Expression
3.4. Apoptosis/Proliferation Ratio
3.5. Lymphocytes T and B Specific Markers and IL-6 Expression
3.6. Renal Fibrosis (Collagen Fiber Thickening)
4. Discussion
5. Conclusions
- The finasteride treatment of adult male rats led to a decrease in androgen receptor expression and its cellular translocation within the kidney cortex.
- The pathomorphological changes (glomerulosclerosis, tubulosclerosis, dysplastic glomeruli, and tubules with lumen dilatation) in rats’ kidneys with disturbed steroid hormone imbalance were associated with the diminished expression of intracellular junctional proteins.
- The changed apoptotic/proliferating ratio of nephron cells and the increase in the numberof lymphocytes in the area of pathologically altered convoluted tubules were accompaniedby impaired androgen/estrogen homeostasis.
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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DHT (ng/mL) | T (ng/mL) | E2 (pg/mL) | |||
---|---|---|---|---|---|
Control | Fin | Control | Fin | Control | Fin |
0.67 ± 0.03 | 0.25 ± 0.09 ** vs. Control | 1.53 ± 0.19 | 0.57 ± 0.25 ** vs. Control | 56.28 ± 9.47 | 31.33 ± 3.63 |
Region | AR | |
---|---|---|
Control | Fin | |
RC | 0.14 ± 0.12 | 0.06 ± 0.03 |
PCT | 0.69 ± 0.32 | 0.16 ± 0.17 * |
DCT | 0.91 ± 0.12 | 0.5 ± 0.26 * |
Occludin | Control | Fin |
---|---|---|
RC mean ± SD | 100% (1) 1 ± 0 | 100% (1) 1 ± 0 |
PCT mean ± SD | 18.5% (1); 81.5% (0) 0.185 ± 0.39 | 33.3% (1); 66.6% (0) 0.33 ± 0.48 |
DCT mean ± SD | 58% (2); 42% (1) 1.58 ± 0.5 | 40% (2); 60 % (1) 1.4 ± 0.54 |
Connexin 43 | ||
RC mean ± SD | 100% (1) 1 ± 0 | 66.6% (2); 33.3% (1) 1.67 ± 0.58 *** |
PCT mean ± SD | 24% (3); 24% (2); 52% (1) 1.71 ± 0.84 | 54.5% (3); 31.8% (2); 9.2% (1); 4.5% (0) 2.36 ± 0.84 * |
DCT mean ± SD | 33.3% (4); 50% (3); 16.6% (2) 3.62 ± 0.71 | 80% (4); 20% (3) 3.8 ± 0.44 |
E-cadherin | ||
RC mean ± SD | 100% (2) 2 ± 0 | 100% (1) 1 ± 0 *** |
PCT mean ± SD | 48,2% (2); 51.8% (1) 1.48 ± 0.51 | 7.2% (2); 17.8% (1); 75% (0) 0.32 ± 0.61 *** |
DCT mean ± SD | 42.8% (4); 57.2% (3) 3.43 ± 0.51 | 31.6% (2); 68.4% (1) 1.3 ± 0.47 *** |
N-cadherin | ||
RC mean ± SD | 100% (3) 3 ± 0 | 100% (1) 1 ± 0 *** |
PCT mean ± SD | 28,6 (1); 71.4% (0) 1.83 ± 0.41 | 21% (2); 52.6% (1); 26.4% (0) 0.95 ± 0.7 ** |
DCT mean ± SD | 53.3% (3); 46.6% (2) 2.57 ± 0.5 | 83.3% (2); 16,6% (1) 0.28 ± 0.46 *** |
β-catenin | ||
RC mean ± SD | 100% (1) 1 ± 0 | 100% (1) 1 ± 0 |
PCT mean ± SD | 45% (2); 54% (1) 1.46 ± 0.5 | 27.8% (1); 72.2% (0) 0.28 ± 0.45 |
DCT mean ± SD | 62% (2); 28,6 (2); 9.4% (3) 3.33 ± 0.9 | 16.7% (4); 55.5% (3); 27.8% (2) 2.89 ± 0.68 |
Apoptosis | Control | Fin |
---|---|---|
TUNEL+DCT | 0.77 ± 0.006 | 0.90 ± 0.0 6 * vs. Control |
TUNEL+PCT | 0.73 ± 0.01 | 0.81 ± 0.14 |
TUNEL+ cells per DCT | 0.18 ± 0.007 | 0.30 ± 0.07 |
TUNEL+ cells per PCT | 0.15 ± 0.002 | 0.21 ± 0.043 |
Proliferation | ||
PCNA+DCT | 0.57 ± 0.14 | 0.86 ± 0.02 * vs. Control |
PCNA+PCT | 0.35 ± 0.17 | 0.46 ± 0.16 |
PCNA+ cells per DCT | 0.08 ± 0.002 | 0.17 ± 0.004 *** vs. Control |
PCNA+ cells per PCT | 0.04 ± 0.01 | 0.07 ± 0.03 |
Thickness of Collagen Fibers | Collagen Type I Fibers (µm) | Collagen Type III Fibers (µm) | ||
---|---|---|---|---|
Control | Fin | Control | Fin | |
in the Interstitial Cortical Region | ||||
Mean ± SD | 1.111 ± 0.469 | 3.298 ± 1.760 vs. Control *** | 1.561 ± 0.755 | 2.121 ± 1.154 |
within the Renal Corpuscle | ||||
Mean ± SD | 2.542 ± 0.974 | 2.287 ± 0.964 | 0.925 ± 0.532 | 1.426 ± 0.569 vs. Control * |
Percentage of Area Occupied by the Collagen in Correlation to the Entire Area of the Section | ||||
Control | Fin | |||
Mean ± SD | 3.63 ± 1.55 | 8.56 ± 0.89 ** |
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Baig, M.S.; Kolasa-Wołosiuk, A.; Pilutin, A.; Safranow, K.; Baranowska-Bosiacka, I.; Kabat-Koperska, J.; Wiszniewska, B. Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study. Int. J. Environ. Res. Public Health 2019, 16, 1726. https://doi.org/10.3390/ijerph16101726
Baig MS, Kolasa-Wołosiuk A, Pilutin A, Safranow K, Baranowska-Bosiacka I, Kabat-Koperska J, Wiszniewska B. Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study. International Journal of Environmental Research and Public Health. 2019; 16(10):1726. https://doi.org/10.3390/ijerph16101726
Chicago/Turabian StyleBaig, Mirza Saim, Agnieszka Kolasa-Wołosiuk, Anna Pilutin, Krzysztof Safranow, Irena Baranowska-Bosiacka, Joanna Kabat-Koperska, and Barbara Wiszniewska. 2019. "Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study" International Journal of Environmental Research and Public Health 16, no. 10: 1726. https://doi.org/10.3390/ijerph16101726
APA StyleBaig, M. S., Kolasa-Wołosiuk, A., Pilutin, A., Safranow, K., Baranowska-Bosiacka, I., Kabat-Koperska, J., & Wiszniewska, B. (2019). Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study. International Journal of Environmental Research and Public Health, 16(10), 1726. https://doi.org/10.3390/ijerph16101726