title: Rotenone Attenuates Renal Injury in Aldosterone-Infused Rats by Inhibiting Oxidative Stress, Mitochondrial Dysfunction, and Inflammasome Activation.
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.
  
  
  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.
authors.affiliation: Division of Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China (mainland).
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, Shanghai, China (mainland).
authors.forename: Chengyan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, Shanghai, China (mainland).
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, Shanghai, China (mainland).
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000450:Aldosterone / Q000737:chemistry*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000293:injuries* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D011507:Proteinuria / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012402:Rotenone / Q000737:chemistry* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D017382:Reactive Oxygen Species; C498145:Rela protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D051996:Transcription Factor RelA; D012402:Rotenone; D000450:Aldosterone; D008315:Malondialdehyde; D000255:Adenosine Triphosphate