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SGLT2 inhibition mitigates transition from acute kidney injury to chronic kidney disease by suppressing ferroptosis.
Hirashima, Yutaro; Nakano, Toshiaki; Torisu, Kumiko; Aihara, Seishi; Wakisaka, Masanori; Kitazono, Takanari.
Afiliación
  • Hirashima Y; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
  • Nakano T; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. nakano.toshiaki.455@m.kyushu-u.ac.jp.
  • Torisu K; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
  • Aihara S; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Wakisaka M; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
  • Kitazono T; Wakisaka Internal Medicine, Fukuoka, Japan.
Sci Rep ; 14(1): 20386, 2024 09 02.
Article en En | MEDLINE | ID: mdl-39223189
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Renal Crónica / Lesión Renal Aguda / Inhibidores del Cotransportador de Sodio-Glucosa 2 / Ferroptosis / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Renal Crónica / Lesión Renal Aguda / Inhibidores del Cotransportador de Sodio-Glucosa 2 / Ferroptosis / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido