Effects of an immunosuppressive treatment on the rat prostate.
The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three-drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins.
Department of Histology and Developmental Biology, Pomeranian Medical University.
Marta
M
Grabowska
Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University.
Karolina
K
Kędzierska
Department of Physiology, Cytobiology and Proteomics, West Pomeranian University of Technology.
Katarzyna
K
Michałek
Department of Physiology, Pomeranian Medical University.
Sylwia
S
Słuczanowska-Głąbowska
Department of Microbiology and Applied Biotechnology, West Pomeranian University of Technology.
Maciej
M
Grabowski
Department of Histology and Developmental Biology, Pomeranian Medical University.
Małgorzata
M
Piasecka
Department of Pathology, West Pomeranian Oncology Center.
Andrzej
A
Kram
Department of Medical Rehabilitation, Pomeranian Medical University, Szczecin, Poland.
Iwona
I
Rotter
Department of Histology and Developmental Biology, Pomeranian Medical University.
Aleksandra
A
Rył
Department of Histology and Developmental Biology, Pomeranian Medical University.
Maria
M
Laszczyńska
PCNA; cytokeratin; desmin; immunosuppressants; rat prostate; ultrastructure
Prostate. 1995 Nov;27(5):258-68
7479393
Scand J Immunol. 2002 Oct;56(4):353-60
12234256
PLoS One. 2015 Mar 27;10(3):e0120939
25816221
Med Electron Microsc. 2003 Sep;36(3):183-91
14505063
Exp Cell Res. 2004 Nov 15;301(1):1-7
15501438
Arterioscler Thromb Vasc Biol. 2013 May;33(5):1028-35
23493289
Transplant Proc. 1988 Jun;20(3 Suppl 3):1005-10
3133851
Clin Invest Med. 2008;31(1):E8-E15
18312749
Transpl Int. 2008 Oct;21(10):992-8
18657090
Biomed Res Int. 2013;2013:690382
23936832
Eur Urol. 1996;29(3):345-54
8740022
Exp Cell Res. 2007 Jun 10;313(10):2021-32
17434482
Eur Respir J. 2004 Jan;23 (1):159-71
14738248
Transplantation. 2003 Aug 15;76(3):463-70
12923430
Transplantation. 2012 May 15;93(9):874-9
22357177
Early Hum Dev. 1991 Jul;26(1):61-7
1914989
Transplantation. 2003 Jan 15;75(1):54-9
12544871
Development. 2002 Apr;129(8):1905-12
11934856
Biochem Biophys Res Commun. 1998 Aug 10;249(1):226-30
9705862
J Am Soc Nephrol. 1999 Jun;10 (6):1366-80
10361877
Transplant Proc. 2013 Mar;45(2):763-9
23498818
Histol Histopathol. 2015 Sep;30(9):1089-100
25772584
Kidney Int. 2003 Sep;64(3):864-73
12911536
Arch Dermatol. 1977 Jul;113(7):930-2
879814
J Cell Biol. 2001 Oct 29;155(3):415-26
11684708
Am J Kidney Dis. 2001 Sep;38(3):580-7
11532692
Folia Morphol (Warsz). 1981;40(1):63-72
6981547
Transplantation. 2000 May 27;69(10):2121-4
10852609
Nutrition. 2005 Jun;21(6):775-7
15925305
J Pathol. 2001 Dec;195(5):563-70
11745692
Histol Histopathol. 2010 Feb;25(2):189-96
20017105
BMC Complement Altern Med. 2013 Feb 13;13:30
23406403
Histol Histopathol. 1996 Oct;11(4):889-94
8930631
Prostate. 1987;10(3):245-56
2884651
Braz J Med Biol Res. 2004 Dec;37(12):1819-30
15558188
Transplantation. 2003 Sep 15;76(5):885-6
14501876
Reprod Biol Endocrinol. 2009 Feb 25;7:19
19243597
Hum Exp Toxicol. 2012 Dec;31(12):1262-70
22549095
J Clin Invest. 1997 May 1;99(9):2094-9
9151781
Br J Urol. 1995 Jun;75 Suppl 1:27-33
7613855
J Proteome Res. 2010 Feb 5;9(2):865-75
19994912
Curr Opin Nephrol Hypertens. 2007 Nov;16(6):523-8
18089965
Ai Zheng. 2009 Aug;28(8):851-5
19664332
J Cell Biol. 2000 Apr 3;149(1):17-22
10747083
Lab Anim. 2011 Jul;45(3):145-53
21498639
Nephrol Dial Transplant. 2008 Jul;23 (7):2374-80
18283085
Virchows Arch A Pathol Anat Histopathol. 1992;421(2):157-61
1381129
Annu Rev Biochem. 1994;63:345-82
7979242
Lab Anim. 2005 Jan;39(1):45-57
15703124
MAbs. 2010 Mar-Apr;2(2):148-56
20150766
Clin Cancer Res. 2003 Oct 15;9(13):4792-801
14581350
N Engl J Med. 2010 Oct 7;363(15):1451-62
20925547
J Clin Invest. 1996 Nov 15;98(10):2277-83
8941644
J Urol. 1993 Jan;149(1):165-9
8093265
J Androl. 2004 Jan-Feb;25(1):50-6
14662786
Clin Exp Immunol. 1994 Dec;98(3):351-7
7994898
Pediatr Surg Int. 1998 Jul;13(5-6):388-91
9639624
Am J Nephrol. 2011;33(6):558-66
21613783
Transplantation. 1991 Sep;52(3):571-4
1716801
Adv Exp Med Biol. 1991;283:847-51
1712536
Blood Purif. 2007;25(5-6):466-72
18087149
Transplantation. 2009 Aug 15;88(3 Suppl):S20-3
19667957