Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy
Mitochondrial abnormality has been shown in many kidney disease models. However, its role in the pathogenesis of chronic kidney diseases (CKDs) is still uncertain. In present study, a mitochondrial complex I inhibitor rotenone was applied to the mice subjected to unilateral ureteral obstruction (UUO...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/670106 |
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| author | Ying Sun Yue Zhang Daqiang Zhao Guixia Ding Songming Huang Aihua Zhang Zhanjun Jia |
| author_facet | Ying Sun Yue Zhang Daqiang Zhao Guixia Ding Songming Huang Aihua Zhang Zhanjun Jia |
| author_sort | Ying Sun |
| collection | DOAJ |
| description | Mitochondrial abnormality has been shown in many kidney disease models. However, its role in the pathogenesis of chronic kidney diseases (CKDs) is still uncertain. In present study, a mitochondrial complex I inhibitor rotenone was applied to the mice subjected to unilateral ureteral obstruction (UUO). Following 7-days rotenone treatment, a remarkable attenuation of tubular injury was detected by PAS staining. In line with the improvement of kidney morphology, rotenone remarkably blunted fibrotic response as shown by downregulation of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), collagen I, collagen III, and α-SMA, paralleled with a substantial decrease of TGF-β1. Meanwhile, the oxidative stress markers thiobarbituric acid-reactive substances (TBARS) and heme oxygenase 1 (HO-1) and inflammatory markers TNF-α, IL-1β, and ICAM-1 were markedly decreased. More importantly, the reduction of mitochondrial DNA copy number and mitochondrial NADH dehydrogenase subunit 1 (mtND1) expression in obstructed kidneys was moderately but significantly restored by rotenone, suggesting an amelioration of mitochondrial injury. Collectively, mitochondrial complex I inhibitor rotenone protected kidneys against obstructive injury possibly via inhibition of mitochondrial oxidative stress, inflammation, and fibrosis, suggesting an important role of mitochondrial dysfunction in the pathogenesis of obstructive kidney disease. |
| format | Article |
| id | doaj-art-2de01ea88cdf4e79b7db7f3ef5e88980 |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2de01ea88cdf4e79b7db7f3ef5e889802025-08-20T03:20:26ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/670106670106Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive UropathyYing Sun0Yue Zhang1Daqiang Zhao2Guixia Ding3Songming Huang4Aihua Zhang5Zhanjun Jia6Nanjing Key Laboratory of Pediatrics, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, ChinaNanjing Key Laboratory of Pediatrics, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, ChinaDepartment of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Tianhe District, Guangzhou 510630, ChinaNanjing Key Laboratory of Pediatrics, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, ChinaNanjing Key Laboratory of Pediatrics, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, ChinaNanjing Key Laboratory of Pediatrics, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, ChinaNanjing Key Laboratory of Pediatrics, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, ChinaMitochondrial abnormality has been shown in many kidney disease models. However, its role in the pathogenesis of chronic kidney diseases (CKDs) is still uncertain. In present study, a mitochondrial complex I inhibitor rotenone was applied to the mice subjected to unilateral ureteral obstruction (UUO). Following 7-days rotenone treatment, a remarkable attenuation of tubular injury was detected by PAS staining. In line with the improvement of kidney morphology, rotenone remarkably blunted fibrotic response as shown by downregulation of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), collagen I, collagen III, and α-SMA, paralleled with a substantial decrease of TGF-β1. Meanwhile, the oxidative stress markers thiobarbituric acid-reactive substances (TBARS) and heme oxygenase 1 (HO-1) and inflammatory markers TNF-α, IL-1β, and ICAM-1 were markedly decreased. More importantly, the reduction of mitochondrial DNA copy number and mitochondrial NADH dehydrogenase subunit 1 (mtND1) expression in obstructed kidneys was moderately but significantly restored by rotenone, suggesting an amelioration of mitochondrial injury. Collectively, mitochondrial complex I inhibitor rotenone protected kidneys against obstructive injury possibly via inhibition of mitochondrial oxidative stress, inflammation, and fibrosis, suggesting an important role of mitochondrial dysfunction in the pathogenesis of obstructive kidney disease.http://dx.doi.org/10.1155/2014/670106 |
| spellingShingle | Ying Sun Yue Zhang Daqiang Zhao Guixia Ding Songming Huang Aihua Zhang Zhanjun Jia Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy Mediators of Inflammation |
| title | Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy |
| title_full | Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy |
| title_fullStr | Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy |
| title_full_unstemmed | Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy |
| title_short | Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy |
| title_sort | rotenone remarkably attenuates oxidative stress inflammation and fibrosis in chronic obstructive uropathy |
| url | http://dx.doi.org/10.1155/2014/670106 |
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