Rotenone Attenuates Renal Injury in Aldosterone-Infused Rats by Inhibiting Oxidative Stress, Mitochondrial Dysfunction, and Inflammasome Activation

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/Methods: Sprague-Dawley rats were divided into 3 groups: vehicle-treated, aldosterone-infused, and aldosterone plus ro-tenone. 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 aldoste-rone-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 me-diators NF-kB p65 and CTGF were upregulated; and NLRP3 inflammasome and its related target proteins, IL-1b and IL-18, were also increased. Treatment with rotenone, an inhibitor of mitochondrial complex I, significant-ly attenuated oxidative stress, mitochondrial dysfunction, and inflammasome response in aldosterone-infused rats