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Rotenone Attenuates Renal Injury in Aldosterone-Infused Rats by Inhibiting
Oxidative Stress, Mitochondrial Dysfunction, and Inflammasome Activation
#MMPMID26474533
Ding W
; Xu C
; Wang B
; Zhang M
Med Sci Monit
2015[Oct]; 21
(?): 3136-43
PMID26474533
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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-?B p65 and CTGF were upregulated; and NLRP3 inflammasome and its related
target proteins, IL-1? 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.
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