17 October 2015 : Animal Research
Rotenone Attenuates Renal Injury in Aldosterone-Infused Rats by Inhibiting Oxidative Stress, Mitochondrial Dysfunction, and Inflammasome Activation
Wei DingAB, Chengyan XuC, Bin WangE, Minmin ZhangDFGDOI: 10.12659/MSM.895945
Med Sci Monit 2015; 21:3136-3143
Abstract
BACKGROUND: Reactive oxygen species (ROS) and inflammation both contribute to the progression of aldosterone-induced renal injury. To better understand the underlying mechanisms, we examined mitochondrial dysfunction and NLRP3 inflammasome activation in aldosterone-infused rats, and explored the role of rotenone in attenuating these injuries.
MATERIAL AND METHODS: Sprague-Dawley rats were divided into 3 groups: vehicle-treated, aldosterone-infused, and aldosterone plus rotenone. Renal damage was evaluated using PAS staining and electron microscopy. Levels of ROS were measured from renal tissue and serum; immunohistochemistry analysis examined the inflammation pathway; Western blot and real-time PCR assessed NLRP3 inflammasome activity.
RESULTS: Glomerular segmental sclerosis, foot process effacement, and proteinuria were demonstrated in the aldosterone-infused rats. Specifically, the thiobarbituric acid-reactive substances (TBARS) oxidative stress marker, MDA, was significantly increased; ATP content and mtDNA copy number were markedly decreased; inflammatory mediators NF-κB p65 and CTGF were upregulated; and NLRP3 inflammasome and its related target proteins, IL-1β and IL-18, were also increased. Treatment with rotenone, an inhibitor of mitochondrial complex I, significantly attenuated oxidative stress, mitochondrial dysfunction, and inflammasome response in aldosterone-infused rats.
CONCLUSIONS: Rotenone ameliorated aldosterone-infused renal injury, possibly by inhibiting oxidative stress, mitochondrial dysfunction, and NLRP3 inflammasome activity. These results provide novel evidence for the role of rotenone in aldosterone-induced renal injury or other chronic kidney disease.
Keywords: Aldosterone - chemistry, Adenosine Triphosphate - chemistry, Carrier Proteins - metabolism, DNA, Mitochondrial - metabolism, Glomerulosclerosis, Focal Segmental - pathology, Inflammasomes - metabolism, Inflammation - metabolism, Kidney - pathology, Malondialdehyde - chemistry, Microscopy, Electron, Mitochondria - pathology, Proteinuria - pathology, Reactive Oxygen Species - metabolism, Real-Time Polymerase Chain Reaction, Rotenone - metabolism, Thiobarbituric Acid Reactive Substances - chemistry, Transcription Factor RelA - metabolism
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
15 Apr 2024 : Laboratory Research
The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in OsteoarthritisMed Sci Monit In Press; DOI: 10.12659/MSM.943738
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952