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
1246 6
Editorial
01 December 2023 : Editorial
Editorial: Outbreaks of Post-Pandemic Childhood Pneumonia and the Re-Emergence of Endemic Respiratory InfectionsDOI: 10.12659/MSM.943312
Med Sci Monit 2023; 29:e943312
In Press
04 Dec 2023 : Animal Research
Effects of Intrathecal Ketamine on Cerebrospinal Fluid Levels of Brain-Derived Neurotrophic Factor and Mech...Med Sci Monit In Press; DOI:
01 Dec 2023 : Clinical Research
Risk Factors and Clinical Outcomes of COVID-19 Infection in Multiple Sclerosis Patients: A Retrospective St...Med Sci Monit In Press; DOI:
30 Nov 2023 : Review article
Decoding the Neurological Sequelae of General Anesthesia: A ReviewMed Sci Monit In Press; DOI:
30 Nov 2023 : Clinical Research
Enhanced Pain Relief and Muscle Growth in Individuals with Low Back Instability: The Impact of Blood Flow R...Med Sci Monit In Press; DOI:
Most Viewed Current Articles
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
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
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292