Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation
Methotrexate (MTX) is a potent anti-cancer drug, commonly associated with nephrotoxicity via the induction of oxidative stress and apoptosis with alteration of renal water channel proteins, namely aquaporins (AQPs). Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) have shown cytoprotective e...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Mosaab Salah El-din El-Agawy Alaa Mohamed Mohamed Badawy Mohammed R. Rabei Mohamed Mahmoud Abdelraheem Elshaer Eman Mohamad El Nashar Mansour A. Alghamdi Mohammed A. Alshehri Hassan Reda Hassan Elsayed |
| author_facet | Mosaab Salah El-din El-Agawy Alaa Mohamed Mohamed Badawy Mohammed R. Rabei Mohamed Mahmoud Abdelraheem Elshaer Eman Mohamad El Nashar Mansour A. Alghamdi Mohammed A. Alshehri Hassan Reda Hassan Elsayed |
| author_sort | Mosaab Salah El-din El-Agawy |
| collection | DOAJ |
| description | Methotrexate (MTX) is a potent anti-cancer drug, commonly associated with nephrotoxicity via the induction of oxidative stress and apoptosis with alteration of renal water channel proteins, namely aquaporins (AQPs). Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) have shown cytoprotective effects through their anti-oxidant and antiapoptotic activities. The present study aims for the first time to explore the role of LC-PUFA against MTX-induced nephrotoxicity. Rats were divided into the following groups: saline control, LC-PUFA control, MTX, MTX + LC-PUFA (150 mg/kg), or MTX + LC-PUFA (300 mg/kg). Then, H&E staining and immunohistochemical staining for the anti-apoptosis marker B-cell lymphoma 2 (BCL-2), the apoptosis marker BCL2-Associated X Protein (BAX), the proinflammatory marker Nuclear factor kappa B (NF-kB), AQPs 1 and 2 were performed in kidney sections with an assessment of renal oxidative stress. The MTX caused a renal histopathological alteration, upregulated renal BAX and NF-kB, downregulated Bcl-2 and AQP1, altered the distribution of AQP2, and caused oxidative stress. The LC-PUFA attenuated the pathological changes and decreased renal BAX and NF-kB, increased BCL-2 and AQP1, restored the normal distribution of AQP2, and decreased the oxidative stress. Therefore, LC-PUFA is a good adjuvant to MTX to prevent its adverse effects on kidneys through its antiapoptotic, antioxidant, and anti-inflammatory effect and its role in the restoration of the expression of AQPs 1 and 2. |
| first_indexed | 2024-03-09T19:01:49Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:01:49Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a65b20f5551d4f14a21a5d48490967532023-11-24T04:57:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211279410.3390/ijms232112794Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids SupplementationMosaab Salah El-din El-Agawy0Alaa Mohamed Mohamed Badawy1Mohammed R. Rabei2Mohamed Mahmoud Abdelraheem Elshaer3Eman Mohamad El Nashar4Mansour A. Alghamdi5Mohammed A. Alshehri6Hassan Reda Hassan Elsayed7Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptDepartment of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi ArabiaNephrology Section, Internal Medicine Department, College of Medicine, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptMethotrexate (MTX) is a potent anti-cancer drug, commonly associated with nephrotoxicity via the induction of oxidative stress and apoptosis with alteration of renal water channel proteins, namely aquaporins (AQPs). Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) have shown cytoprotective effects through their anti-oxidant and antiapoptotic activities. The present study aims for the first time to explore the role of LC-PUFA against MTX-induced nephrotoxicity. Rats were divided into the following groups: saline control, LC-PUFA control, MTX, MTX + LC-PUFA (150 mg/kg), or MTX + LC-PUFA (300 mg/kg). Then, H&E staining and immunohistochemical staining for the anti-apoptosis marker B-cell lymphoma 2 (BCL-2), the apoptosis marker BCL2-Associated X Protein (BAX), the proinflammatory marker Nuclear factor kappa B (NF-kB), AQPs 1 and 2 were performed in kidney sections with an assessment of renal oxidative stress. The MTX caused a renal histopathological alteration, upregulated renal BAX and NF-kB, downregulated Bcl-2 and AQP1, altered the distribution of AQP2, and caused oxidative stress. The LC-PUFA attenuated the pathological changes and decreased renal BAX and NF-kB, increased BCL-2 and AQP1, restored the normal distribution of AQP2, and decreased the oxidative stress. Therefore, LC-PUFA is a good adjuvant to MTX to prevent its adverse effects on kidneys through its antiapoptotic, antioxidant, and anti-inflammatory effect and its role in the restoration of the expression of AQPs 1 and 2.https://www.mdpi.com/1422-0067/23/21/12794methotrexatekidneyomega-3 fatty acidsapoptosisaquaporinsoxidative stress |
| spellingShingle | Mosaab Salah El-din El-Agawy Alaa Mohamed Mohamed Badawy Mohammed R. Rabei Mohamed Mahmoud Abdelraheem Elshaer Eman Mohamad El Nashar Mansour A. Alghamdi Mohammed A. Alshehri Hassan Reda Hassan Elsayed Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation International Journal of Molecular Sciences methotrexate kidney omega-3 fatty acids apoptosis aquaporins oxidative stress |
| title | Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation |
| title_full | Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation |
| title_fullStr | Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation |
| title_full_unstemmed | Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation |
| title_short | Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation |
| title_sort | methotrexate induced alteration of renal aquaporins 1 and 2 oxidative stress and tubular apoptosis can be attenuated by omega 3 fatty acids supplementation |
| topic | methotrexate kidney omega-3 fatty acids apoptosis aquaporins oxidative stress |
| url | https://www.mdpi.com/1422-0067/23/21/12794 |
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