Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation.
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 Information
Mosaab Salah El-Din El-Agawy: Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Alaa Mohamed Mohamed Badawy: Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Mohammed R Rabei: Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. ORCID
Mohamed Mahmoud Abdelraheem Elshaer: Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.
Eman Mohamad El Nashar: Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia. ORCID
Mansour A Alghamdi: Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia. ORCID
Mohammed A Alshehri: Nephrology Section, Internal Medicine Department, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia. ORCID
Hassan Reda Hassan Elsayed: Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. ORCID
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.
