Efficacy of a mitochondrion-targeting agent for reducing the level of urinary protein in rats with puromycin aminonucleoside-induced minimal-change nephrotic syndrome


Autoři: Yuko Fujii aff001;  Hideki Matsumura aff001;  Satoshi Yamazaki aff001;  Akihiko Shirasu aff002;  Hyogo Nakakura aff003;  Tohru Ogihara aff001;  Akira Ashida aff001
Působiště autorů: Department of Pediatrics, Osaka Medical College, Takatsuki, Osaka, Japan aff001;  Department of Pediatrics, Hirakata City Hospital, Hirakata, Osaka, Japan aff002;  Department of Hemodialysis and Apheresis, Arisawa General Hospital, Hirakata, Osaka, Japan aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0227414

Souhrn

Background

Oxidative 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 methods

Thirty 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.

Results

Urinary 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).

Conclusions

This 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.

Klíčová slova:

Electron microscopy – Ethanol – Excretion – Glomeruli – Kidneys – Mitochondria – Oxidative stress – Urine


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