Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction
Obstructive nephropathy (ON), characterized by urine flow disruption, can induce chronic kidney disease (CKD). Although the release of the obstruction is performed as the primary intervention, renal pathology often persists and progresses. Accordingly, the murine model of releasing unilateral ureter...
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MDPI AG
2025-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/3/288 |
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| author | Ana Karina Aranda-Rivera Isabel Amador-Martínez Omar Emiliano Aparicio-Trejo Juan Carlos León-Contreras Rogelio Hernández-Pando Emma Saavedra Fernando E. García-Arroyo José Pedraza-Chaverri Laura Gabriela Sánchez-Lozada Edilia Tapia |
| author_facet | Ana Karina Aranda-Rivera Isabel Amador-Martínez Omar Emiliano Aparicio-Trejo Juan Carlos León-Contreras Rogelio Hernández-Pando Emma Saavedra Fernando E. García-Arroyo José Pedraza-Chaverri Laura Gabriela Sánchez-Lozada Edilia Tapia |
| author_sort | Ana Karina Aranda-Rivera |
| collection | DOAJ |
| description | Obstructive nephropathy (ON), characterized by urine flow disruption, can induce chronic kidney disease (CKD). Although the release of the obstruction is performed as the primary intervention, renal pathology often persists and progresses. Accordingly, the murine model of releasing unilateral ureteral obstruction (RUUO) is valuable for investigating the molecular events underlying renal damage after obstruction release. Remarkably, after RUUO, disturbances such as oxidative stress, inflammation, lipid accumulation, and fibrosis continue to increase. Mitochondrial dysfunction contributes to fibrosis in the UUO model, but its role in RUUO remains unclear. Additionally, the impact of using antioxidants to restore mitochondrial function and prevent renal fibrosis in RUUO has not been determined. This study aimed to determine the therapeutic effect of pre-administering the antioxidant sulforaphane (SFN) in the RUUO model. SFN was administered 1 day before RUUO to evaluate mitochondrial biogenesis, fatty acids (FA) metabolism, bioenergetics, dynamics, and mitophagy/autophagy mechanisms in the kidney. Our data demonstrated that SFN enhanced mitochondrial biogenesis and reestablished mitochondrial oxygen consumption and β-oxidation. These effects collectively reduced lipid accumulation and normalized mitochondrial dynamics, mitophagy, and autophagy, thereby mitigating fibrosis after obstruction. Our findings suggest that SFN holds promise as a potential therapeutic agent in ON-induced CKD progression in RUUO and opens new avenues in studying antioxidant molecules to treat this disease. |
| format | Article |
| id | doaj-art-3f6feacf5ab34d0ebdc7f5e2ed143758 |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-3f6feacf5ab34d0ebdc7f5e2ed1437582025-08-20T02:42:35ZengMDPI AGAntioxidants2076-39212025-02-0114328810.3390/antiox14030288Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral ObstructionAna Karina Aranda-Rivera0Isabel Amador-Martínez1Omar Emiliano Aparicio-Trejo2Juan Carlos León-Contreras3Rogelio Hernández-Pando4Emma Saavedra5Fernando E. García-Arroyo6José Pedraza-Chaverri7Laura Gabriela Sánchez-Lozada8Edilia Tapia9Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, Mexico City 04510, MexicoDepartamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, Mexico City 04510, MexicoDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, MexicoDepartamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City 14080, MexicoDepartamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City 14080, MexicoDepartamento de Bioquímica, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City 14080, MexicoDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, MexicoDepartamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, Mexico City 04510, MexicoDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, MexicoDepartamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, MexicoObstructive nephropathy (ON), characterized by urine flow disruption, can induce chronic kidney disease (CKD). Although the release of the obstruction is performed as the primary intervention, renal pathology often persists and progresses. Accordingly, the murine model of releasing unilateral ureteral obstruction (RUUO) is valuable for investigating the molecular events underlying renal damage after obstruction release. Remarkably, after RUUO, disturbances such as oxidative stress, inflammation, lipid accumulation, and fibrosis continue to increase. Mitochondrial dysfunction contributes to fibrosis in the UUO model, but its role in RUUO remains unclear. Additionally, the impact of using antioxidants to restore mitochondrial function and prevent renal fibrosis in RUUO has not been determined. This study aimed to determine the therapeutic effect of pre-administering the antioxidant sulforaphane (SFN) in the RUUO model. SFN was administered 1 day before RUUO to evaluate mitochondrial biogenesis, fatty acids (FA) metabolism, bioenergetics, dynamics, and mitophagy/autophagy mechanisms in the kidney. Our data demonstrated that SFN enhanced mitochondrial biogenesis and reestablished mitochondrial oxygen consumption and β-oxidation. These effects collectively reduced lipid accumulation and normalized mitochondrial dynamics, mitophagy, and autophagy, thereby mitigating fibrosis after obstruction. Our findings suggest that SFN holds promise as a potential therapeutic agent in ON-induced CKD progression in RUUO and opens new avenues in studying antioxidant molecules to treat this disease.https://www.mdpi.com/2076-3921/14/3/288obstructive nephropathy (ON)sulforaphane (SFN)mitochondrial biogenesisβ-oxidationfatty acid metabolismmitochondrial dynamics |
| spellingShingle | Ana Karina Aranda-Rivera Isabel Amador-Martínez Omar Emiliano Aparicio-Trejo Juan Carlos León-Contreras Rogelio Hernández-Pando Emma Saavedra Fernando E. García-Arroyo José Pedraza-Chaverri Laura Gabriela Sánchez-Lozada Edilia Tapia Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction Antioxidants obstructive nephropathy (ON) sulforaphane (SFN) mitochondrial biogenesis β-oxidation fatty acid metabolism mitochondrial dynamics |
| title | Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction |
| title_full | Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction |
| title_fullStr | Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction |
| title_full_unstemmed | Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction |
| title_short | Sulforaphane Restores Mitochondrial β-Oxidation and Reduces Renal Lipid Accumulation in a Model of Releasing Unilateral Ureteral Obstruction |
| title_sort | sulforaphane restores mitochondrial β oxidation and reduces renal lipid accumulation in a model of releasing unilateral ureteral obstruction |
| topic | obstructive nephropathy (ON) sulforaphane (SFN) mitochondrial biogenesis β-oxidation fatty acid metabolism mitochondrial dynamics |
| url | https://www.mdpi.com/2076-3921/14/3/288 |
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