Androgen receptor blockade by flutamide down-regulates renal fibrosis, inflammation, and apoptosis pathways in male rats.
Life Sci
; 323: 121697, 2023 Jun 15.
Article
in En
| MEDLINE
| ID: mdl-37061126
ABSTRACT
AIM:
this study aims to explore the effect of androgen receptor (AR) blockade by flutamide on some renal pathologic changes such as inflammation, apoptosis, and fibrosis in male rats. MAINMETHODS:
Firstly, we investigated the potential effect of AR blockade on renal inflammatory intermediates including IL-1ß, IL-6, TNF-α, NF-Òß proteins, and the renal gene expression of NF-Òß. Besides inflammation, we also assessed the apoptosis pathways including the caspases 3 & 9, mTOR, pAKT proteins, and BAX gene expression. Besides inflammation and apoptosis pathways, we also investigated the effect of androgen blockade on renal fibrosis intermediates including vimentin, TGFß-1, α-SMA, MMP-9, collagen type-III, collagen type-IV, and the renal expression of the col1A1 gene. Besides previous pathological pathways, we assessed the expression of chloride channel protein-5 (ClC-5), as an important regulator of many renal pathological changes. Finally, we assessed the impact of previous pathological changes on renal function at biochemical and pathological levels. KEYFINDINGS:
We found that AR blockade by flutamide was associated with the down-regulation of renal inflammation, apoptosis, and fibrosis markers. It was associated with expression down-regulation of IL-1ß & IL-6, TNF-α, NF-Òß, caspases 3 & 9, mTOR, MMP-9, collagens, TGFß-1, and α-SMA. Away from down-regulation, we also found that AR blockade has upregulated ClC-5 and pAKT proteins.SIGNIFICANCE:
AR is a major player in androgens-induced nephrotoxicity. AR blockade downregulates renal fibrosis, inflammation, and apoptosis pathways. It may be helpful as a strategy for alleviation of renal side effects associated with some drugs. However; this needs further investigations.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Flutamide
/
Kidney Diseases
Limits:
Animals
Language:
En
Journal:
Life Sci
Year:
2023
Type:
Article
Affiliation country:
Egypt