Bibliographic Details
| Title: |
SGLT2 inhibition mitigates transition from acute kidney injury to chronic kidney disease by suppressing ferroptosis. |
| Authors: |
Hirashima, Yutaro1, Nakano, Toshiaki1 nakano.toshiaki.455@m.kyushu-u.ac.jp, Torisu, Kumiko1,2, Aihara, Seishi1, Wakisaka, Masanori3, Kitazono, Takanari1 |
| Source: |
Scientific Reports. 9/2/2024, Vol. 14 Issue 1, p1-17. 17p. |
| Subject Terms: |
*NUCLEAR factor E2 related factor, *TRANSFERRIN receptors, *GLUTATHIONE peroxidase, *ACUTE kidney failure, *CHRONIC kidney failure, *CARNITINE palmitoyltransferase, *KIDNEY tubules |
| Abstract: |
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be renoprotective in ischemia-reperfusion (I/R) injury, with several proposed mechanisms, though additional mechanisms likely exist. This study investigated the impact of luseogliflozin on kidney fibrosis at 48 h and 1 week post I/R injury in C57BL/6 mice. Luseogliflozin attenuated kidney dysfunction and the acute tubular necrosis score on day 2 post I/R injury, and subsequent fibrosis at 1 week, as determined by Sirius red staining. Metabolomics enrichment analysis of I/R-injured kidneys revealed suppression of the glycolytic system and activation of mitochondrial function under treatment with luseogliflozin. Western blotting showed increased nutrient deprivation signaling with elevated phosphorylated AMP-activated protein kinase and Sirtuin-3 in luseogliflozin-treated kidneys. Luseogliflozin-treated kidneys displayed increased protein levels of carnitine palmitoyl transferase 1α and decreased triglyceride deposition, as determined by oil red O staining, suggesting activated fatty acid oxidation. Luseogliflozin prevented the I/R injury-induced reduction in nuclear factor erythroid 2-related factor 2 activity. Western blotting revealed increased glutathione peroxidase 4 and decreased transferrin receptor protein 1 expression. Immunostaining showed reduced 4-hydroxynonenal and malondialdehyde levels, especially in renal tubules, indicating suppressed ferroptosis. Luseogliflozin may protect the kidney from I/R injury by inhibiting ferroptosis through oxidative stress reduction. [ABSTRACT FROM AUTHOR] |
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