Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage

• Published in: International journal of molecular sciences 2020-09, Vol.21 (18), p.6512
• Main Authors: Aparicio-Trejo, Omar Emiliano, Rojas-Morales, Pedro, Avila-Rojas, Sabino Hazael, León-Contreras, Juan Carlos, Hernández-Pando, Rogelio, Jiménez-Uribe, Alexis Paulina, Prieto-Carrasco, Rodrigo, Sánchez-Lozada, Laura Gabriela, Pedraza-Chaverri, José, Tapia, Edilia
• Format: Article
• Language: English
• Subjects: 5/6 nephrectomy; Adenosine triphosphate; Animals; ATP; ATP synthase; Bioenergetics; chronic kidney disease; Creatinine; Decoupling; Diabetes; Disease Progression; Electron transport; Energy Metabolism; Hemodynamics; Hemodynamics - physiology; Impairment; Kidney - blood supply; Kidney - metabolism; Kidney - pathology; Kidney - surgery; Kidney diseases; Male; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; mitochondrial damage; Nephrectomy; Nephrectomy - adverse effects; Nephrectomy - methods; Organelles; Oxidation; Oxidation-Reduction; Oxidative stress; Oxidative Stress - physiology; Oxygen Consumption - physiology; Postoperative Complications - metabolism; Postoperative Complications - pathology; Rats; Rats, Wistar; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology; Respiration; Respirometry; Surgery; Time Factors; β-oxidation impairment
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21186512

Five-sixths nephrectomy (5/6Nx) model is widely used for studying the mechanisms involved in chronic kidney disease (CKD) progression, a kidney pathology that has increased dramatically in recent years. Mitochondrial impairment is a key mechanism that aggravates CKD progression; however, the information on mitochondrial bioenergetics and redox alterations along a time course in a 5/6Nx model is still limited and in some cases contradictory. Therefore, we performed for the first time a time-course study of mitochondrial alterations by high-resolution respirometry in the 5/6Nx model. Our results show a decrease in mitochondrial β-oxidation at early times, as well as a permanent impairment in adenosine triphosphate (ATP) production in CI-linked respiration, a permanent oxidative state in mitochondria and decoupling of these organelles. These pathological alterations are linked to the early decrease in complex I and ATP synthase activities and to the further decrease in complex III activity. Therefore, our results may suggest that mitochondrial bioenergetics impairment is an early event in renal damage, whose persistence in time aggravates CKD development in the 5/6Nx model.