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2015 ; 2015
(ä): 273784
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Candesartan Mediated Amelioration of Cisplatin-Induced Testicular Damage Is
Associated with Alterations in Expression Patterns of Nephrin and Podocin
#MMPMID26539476
Enatsu N
; Miyake H
; Chiba K
; Fujisawa M
Biomed Res Int
2015[]; 2015
(ä): 273784
PMID26539476
show ga
Nephrin and podocin are known to be closely related to the pharmacological
effects of angiotensin-II receptor blocker (ARB). The objectives of this study
were to investigate the role of nephrin and podocin using cisplatin-induced
testicular damage and to evaluate the effect of ARB. At first, we evaluated the
effects of cisplatin either alone or in combination with ARB candesartan on
changes in expression patterns of nephrin and podocin in the rat testes. We then
conducted in vitro studies to investigate the effects of angiotensin using
cultured Sertoli cells, line TM4. As a result, the expression of nephrin and
podocin was shown to localize around the basal membrane of seminiferous tubules.
Treatment with cisplatin resulted in a marked decrease in the expression of
nephrin and podocin and induced a shift of both proteins from linear to granular
expression patterns, accompanying the increased apoptotic index in the testes;
these changes were partially restored by the additional administration of
candesartan. In vitro studies with TM4 revealed the angiotensin-II mediated
expression changes of nephrin and podocin. These findings suggest that
candesartan can prevent cisplatin-induced testicular damage by regulating
expression patterns of the nephrin-podocin complex in the testes.
|Animals
[MESH]
|Benzimidazoles/*administration & dosage
[MESH]
|Biphenyl Compounds
[MESH]
|Cisplatin/toxicity
[MESH]
|Gene Expression Regulation/drug effects
[MESH]
|Humans
[MESH]
|Intracellular Signaling Peptides and Proteins/*biosynthesis/genetics
[MESH]