Abstract
BackgroundOxidative stress is a major factor responsible for minimal-change nephrotic syndrome (MCNS), which occurs most commonly in children. However, the influence of oxidative stress localized to mitochondria remains unclear. We examined the effect of a mitochondrion-targeting antioxidant, MitoTEMPO, in rats with puromycin aminonucleoside (PAN)-induced MCNS to clarify the degree to which mitochondrial oxidative stress affects MCNS.Materials and methodsThirty Wistar rats were divided into three groups: normal saline group (n = 7), PAN group (n = 12), and PAN + MitoTEMPO group (n = 11). Rats in the PAN and PAN + MitoTEMPO groups received PAN on day 1, and those in the PAN + MitoTEMPO group received MitoTEMPO on days 0 to 9. Whole-day urine samples were collected on days 3 and 9, and samples of glomeruli and blood were taken for measurement of lipid peroxidation products. We also estimated the mitochondrial damage score in podocytes in all 3 groups using electron microscopy.ResultsUrinary protein excretion on day 9 and the levels of lipid peroxidation products in urine, glomeruli, and blood were significantly lower in the PAN + MitoTEMPO group than in the PAN group (p = 0.0019, p = 0.011, p = 0.039, p = 0.030). The mitochondrial damage score in podocytes was significantly lower in the PAN + MitoTEMPO group than in the PAN group (p <0.0001).ConclusionsThis mitochondrion-targeting agent was shown to reduce oxidative stress and mitochondrial damage in a MCNS model. A radical scavenger targeting mitochondria could be a promising drug for treatment of MCNS.
Highlights
It has recently become evident that mitochondrial damage is associated with a wide range of conditions affecting the brain [1], cardiovascular system [2], lungs [3], digestive tract [4] and liver [5], as well as in metabolic diseases and neoplasia [6]
We examined the effect of a mitochondrion-targeting antioxidant, MitoTEMPO, in rats with puromycin aminonucleoside (PAN)induced minimal-change nephrotic syndrome (MCNS) to clarify the degree to which mitochondrial oxidative stress affects MCNS
The mitochondrial damage score in podocytes was significantly lower in the PAN+MitoTEMPO group than in the PAN group (p
Summary
It has recently become evident that mitochondrial damage is associated with a wide range of conditions affecting the brain [1], cardiovascular system [2], lungs [3], digestive tract [4] and liver [5], as well as in metabolic diseases and neoplasia [6]. The pathology of PAN-induced minimal-change nephrotic syndrome (MCNS) has been explained in terms of podocyte damage and apoptosis due to a ROS surge [25, 26]. We have previously reported that alpha-tocopherol and edaravone, radical scavengers that inhibit lipid peroxidation, reduce ROS in rats with PAN-induced MCNS [27, 28]. It has become evident that α-tocopherol and edaravone exert a favorable effect on mitochondria [29, 30] These observations, as well as the fact that mitochondria produce large amounts of ROS, suggest that PAN-induced MCNS may be intimately associated with mitochondrial damage. We examined the effect of a mitochondrion-targeting antioxidant, MitoTEMPO, in rats with puromycin aminonucleoside (PAN)induced MCNS to clarify the degree to which mitochondrial oxidative stress affects MCNS
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