| Autor: |
Sharawy N; Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt., Aboulhoda BE; Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt., Khalifa MM; Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.; Department of Human Physiology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia., Morcos GN; Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.; Department of Basic Medical Sciences, Faculty of Medicine, King Salman International University, South Sinai, Sinai, Egypt., Morsy SAAG; Pathological Sciences Department, MBBS Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia.; Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt., Alghamdi MA; College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia.; Genomics and Personalized Medicine Unit, The Center for Medical and Health Research, King Khalid University, Abha, 62529, Saudi Arabia., Khalifa IM; Clinical Sciences Department, MBBS Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia.; Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Abd Algaleel WA; Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt.; Faculty of Medicine, Galala University, Suez, Egypt. |
| Abstrakt: |
Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation. |
