2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis
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...
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| Format: | Article |
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Multidisciplinary Digital Publishing Institute
2022
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| author | Al-Rabia, Mohammed W. Alfaleh, Mohamed A. Asfour, Hani Z. Alharbi, Waleed S. El-Moselhy, Mohamed A. Alhakamy, Nabil A. Fahmy, Usama A. Ahmed, Osama A. A. Fahmy, Omar Rashad, Omar M. Alamoudi, Abdulmohsin J. Abdel-Naim, Ashraf |
| author_facet | Al-Rabia, Mohammed W. Alfaleh, Mohamed A. Asfour, Hani Z. Alharbi, Waleed S. El-Moselhy, Mohamed A. Alhakamy, Nabil A. Fahmy, Usama A. Ahmed, Osama A. A. Fahmy, Omar Rashad, Omar M. Alamoudi, Abdulmohsin J. Abdel-Naim, Ashraf |
| author_sort | Al-Rabia, Mohammed W. |
| collection | UPM |
| description | 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. |
| first_indexed | 2024-09-25T03:35:45Z |
| format | Article |
| id | upm.eprints-100056 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-09-25T03:35:45Z |
| publishDate | 2022 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | upm.eprints-1000562024-08-05T01:56:12Z http://psasir.upm.edu.my/id/eprint/100056/ 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis Al-Rabia, Mohammed W. Alfaleh, Mohamed A. Asfour, Hani Z. Alharbi, Waleed S. El-Moselhy, Mohamed A. Alhakamy, Nabil A. Fahmy, Usama A. Ahmed, Osama A. A. Fahmy, Omar Rashad, Omar M. Alamoudi, Abdulmohsin J. Abdel-Naim, Ashraf 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. Multidisciplinary Digital Publishing Institute 2022-07-30 Article PeerReviewed Al-Rabia, Mohammed W. and Alfaleh, Mohamed A. and Asfour, Hani Z. and Alharbi, Waleed S. and El-Moselhy, Mohamed A. and Alhakamy, Nabil A. and Fahmy, Usama A. and Ahmed, Osama A. A. and Fahmy, Omar and Rashad, Omar M. and Alamoudi, Abdulmohsin J. and Abdel-Naim, Ashraf (2022) 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis. Antioxidants, 11 (8). art. no. 1499. pp. 1-16. ISSN 2076-3921 https://www.mdpi.com/2076-3921/11/8/1499 10.3390/antiox11081499 |
| spellingShingle | Al-Rabia, Mohammed W. Alfaleh, Mohamed A. Asfour, Hani Z. Alharbi, Waleed S. El-Moselhy, Mohamed A. Alhakamy, Nabil A. Fahmy, Usama A. Ahmed, Osama A. A. Fahmy, Omar Rashad, Omar M. Alamoudi, Abdulmohsin J. Abdel-Naim, Ashraf 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis |
| title | 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis |
| title_full | 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis |
| title_fullStr | 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis |
| title_full_unstemmed | 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis |
| title_short | 2-methoxyestradiol TPGS micelles attenuate cyclosporine A-induced nephrotoxicity in rats through inhibition of TGF-β1 and p-ERK1/2 axis |
| title_sort | 2 methoxyestradiol tpgs micelles attenuate cyclosporine a induced nephrotoxicity in rats through inhibition of tgf β1 and p erk1 2 axis |
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