دورية أكاديمية
أعرض في EDS

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis.

التفاصيل البيبلوغرافية
العنوان: 2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis.
المؤلفون: Al-Rabia MW; Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Alfaleh MA; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Asfour HZ; Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Alharbi WS; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., El-Moselhy MA; Clinical Pharmacy and Pharmacology Department, Ibn Sina National College for Medical Studies, Jeddah 21589, Saudi Arabia.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt., Alhakamy NA; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Fahmy UA; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Ahmed OAA; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Fahmy O; Department of Urology, Universiti Putra Malaysia, Serdang 43400, Malaysia., Rashad OM; Department of Pharmaceutical Technology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt., Alamoudi AJ; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Abdel-Naim AB; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
المصدر: Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2022 Jul 30; Vol. 11 (8). Date of Electronic Publication: 2022 Jul 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101668981 Publication Model: Electronic Cited Medium: Print ISSN: 2076-3921 (Print) Linking ISSN: 20763921 NLM ISO Abbreviation: Antioxidants (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, [2012]-
مستخلص: The immunosuppressant cyclosporine A (CSA) has been linked to serious renal toxic effects. Although 2-methoxyestradiol (2ME) possesses a wide range of pharmacological abilities, it suffers poor bioavailability after oral administration. The purpose of this study was to evaluate the potential of 2ME loaded D-ɑ-tocopheryl polyethylene glycol succinate (TPGS) micelles to prevent CSA-induced nephrotoxicity in rats. A 2ME-TPGS was prepared and showed particle size of 44.3 ± 3.5 nm with good entrapment efficiency and spherical structures. Male Wistar rats were divided into 5 groups, namely: Control, Vehicle, CSA, CSA + 2ME-Raw, and CSA + 2ME-Nano. CSA was injected daily at a SC dose of 20 mg/kg. Both 2ME-Raw and 2ME-Nano were given daily at oral doses of 5 mg/kg. Treatments continued for three successive weeks. 2ME-TPGS exerted significant protective effects against CSA nephrotoxicity. This was evidenced in ameliorating deterioration of renal functions, attenuation of pathological changes in kidney tissues, exerting significant anti-fibrotic, antioxidant, and anti-inflammatory effects together with significant anti-apoptotic effects. Western blot analyses showed both 2ME-Raw and 2ME-Nano significantly inhibited protein expression of TGF-β1 and phospho-ERK (p-ERK). It was observed that 2ME-TPGS, in almost all experiments, exerted superior protective effects as compared with 2ME-Raw. In conclusion, 2ME loaded in a TPGS nanocarrier possesses significant protective activities against CSA-induced kidney injury in rats. This is attributable to 2ME anti-fibrotic, antioxidant, anti-inflammatory, and anti-apoptotic activities which are mediated at least partly by inhibition of TGF-β1/p-ERK axis.
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معلومات مُعتمدة: RG-17-140-42 King Abdulaziz University
فهرسة مساهمة: Keywords: 2-methoxyestradiol; TGF-β1; TPGS; cyclosporine A; nephrotoxicity; p-ERK
تواريخ الأحداث: Date Created: 20220826 Latest Revision: 20220830
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9405159
DOI: 10.3390/antiox11081499
PMID: 36009218
قاعدة البيانات: MEDLINE
الوصف
تدمد:2076-3921
DOI:10.3390/antiox11081499