دورية أكاديمية
أعرض في EDS

Androgen receptor blockade by flutamide down-regulates renal fibrosis, inflammation, and apoptosis pathways in male rats.

التفاصيل البيبلوغرافية
العنوان: Androgen receptor blockade by flutamide down-regulates renal fibrosis, inflammation, and apoptosis pathways in male rats.
المؤلفون: Allam S; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, 32511 Menoufia, Egypt., Elsakka EGE; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt. Electronic address: elsayedelsakka750@azhar.edu.eg., Ismail A; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt. Electronic address: dr.ahmed882010@Azhar.edu.eg., Doghish AS; Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt. Electronic address: ahmed_doghish@azhar.edu.eg., Yehia AM; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt., Elkady MA; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt., Mokhlis HA; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt., Sayed SM; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (girls) Al-Azhar University, Nasr City, Cairo, Egypt., Abd Elaziz AI; Department of Pharmacology, Faculty of Medicine (Boys), Al-Azhar University, Nasr City, Cairo, Egypt., Hashish AA; Basic Medical Sciences Department, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Amin MM; Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt., El Shahat RM; Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt., Mohammed OA; Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt; Department of Clinical Pharmacology, Faculty of Medicine, Bisha University, Bisha 61922, Saudi Arabia.
المصدر: Life sciences [Life Sci] 2023 Jun 15; Vol. 323, pp. 121697. Date of Electronic Publication: 2023 Apr 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
مواضيع طبية MeSH: Flutamide*/pharmacology , Kidney Diseases*, Rats ; Male ; Animals ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Matrix Metalloproteinase 9/metabolism ; Tumor Necrosis Factor-alpha/pharmacology ; Interleukin-6/pharmacology ; NF-kappa B/metabolism ; Androgens/pharmacology ; Fibrosis ; Apoptosis ; TOR Serine-Threonine Kinases ; Inflammation/drug therapy ; Caspases
مستخلص: 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.
Main Methods: Firstly, we investigated the potential effect of AR blockade on renal inflammatory intermediates including IL-1β, IL-6, TNF-α, NF-Қβ proteins, and the renal gene expression of NF-Қβ. 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, TGFβ-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.
Key Findings: 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-1β & IL-6, TNF-α, NF-Қβ, caspases 3 & 9, mTOR, MMP-9, collagens, TGFβ-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.
Competing Interests: Declaration of competing interest The authors state that there are no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Androgen receptors; Apoptosis & ClC-5; Fibrosis; Flutamide; Inflammation
المشرفين على المادة: 76W6J0943E (Flutamide)
0 (Receptors, Androgen)
EC 3.4.24.35 (Matrix Metalloproteinase 9)
0 (Tumor Necrosis Factor-alpha)
0 (Interleukin-6)
0 (NF-kappa B)
0 (Androgens)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
EC 3.4.22.- (Caspases)
تواريخ الأحداث: Date Created: 20230415 Date Completed: 20230508 Latest Revision: 20230508
رمز التحديث: 20240628
DOI: 10.1016/j.lfs.2023.121697
PMID: 37061126
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0631
DOI:10.1016/j.lfs.2023.121697