Key result
Mito-Tempo improves renal function and reduces mitochondrial dysfunction in aldosterone-infused mice.
Why the study?
Mitochondrial dysfunction and Nlrp3 inflammasome activation contribute to chronic kidney disease progression, but in vivo evidence for mitochondria-targeted antioxidant protection is lacking.
Does Mito-Tempo prevent aldosterone-induced renal injury in C57BL/6J mice?
Does Mito-Tempo prevent aldosterone-induced renal injury in C57BL/6J mice?
Mitochondria-targeted antioxidants like Mito-Tempo may attenuate aldosterone-induced renal injury by inhibiting mitochondrial dysfunction and inflammasome activation.
Hypothesis-generating for mitochondrial antioxidants in experimental aldosteronism; leaves open translation to human renal disease.
BACKGROUND/AIMS: Growing evidence suggests mitochondrial dysfunction (MtD) and the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD) progression. We previously reported that Aldosterone (Aldo)-induced renal injury in vitro is directly caused by mitochondrial reactive oxygen species (mtROS)-mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether a mitochondria-targeted antioxidant (Mito-Tempo) could prevent Aldo-induced kidney damage in vivo. METHODS: C57BL/6J mice were treated with Aldo and/or Mito-Tempo (or ethanol as a control) for 4 weeks. Renal injury was evaluated by Periodic Acid-Schiff reagent or Masson's trichrome staining and electron microscopy. ROS were measured by DCFDA fluorescence and ELISA. MtD was determined by real-time PCR and electron microscopy. Activation of the Nlrp3 inflammasome and endoplasmic reticulum stress (ERS) was detected via western blot. RESULTS: Compared with control mice, Aldo-infused mice showed impaired renal function, increased mtROS production and MtD, Nlrp3 inflammasome activation, and elevated ERS. We showed administration of Mito-Tempo significantly improved renal function and MtD, and reduced Nlrp3 inflammasome activation and ERS in vivo. CONCLUSION: Mitochondria-targeted antioxidants may attenuate Aldo-infused renal injury by inhibiting MtD, the Nlrp3 inflammasome, and ERS in vivo. Therefore, targeting mtROS might be an effective strategy for preventing CKD.
No takes yet. Share an insight, caveat, or question.
Ding et al. (2017) studied Aldosterone-induced renal injury. Mito-Tempo vs. ethanol control was evaluated on Renal function, mitochondrial dysfunction, Nlrp3 inflammasome activation, and endoplasmic reticulum stress. Mito-Tempo significantly improved renal function and mitochondrial dysfunction, and reduced Nlrp3 inflammasome activation and endoplasmic reticulum stress in aldosterone-infused mice.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: