DOI： 10.1681/ASN.2024jw0zaqg8

Web of Science

Language：English   Publisher：Scientific Reports  

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.

DOI： 10.1038/s41598-024-71416-0

Web of Science

Scopus

PubMed

Web of Science

Language：English   Publisher：Biochemical and Biophysical Research Communications  

Acute kidney injury is an important global health concern as it is associated with high morbidity and mortality. Polyamines, essential for cell growth and proliferation, are known to inhibit cardiovascular disease. However, under conditions of cellular damage, toxic acrolein is produced from polyamines by the enzyme spermine oxidase (SMOX). We used a mouse renal ischemia-reperfusion model and human proximal tubule cells (HK-2) to investigate whether acrolein exacerbates acute kidney injury by renal tubular cell death. Acrolein visualized by acroleinRED was increased in ischemia-reperfusion kidneys, particularly in tubular cells. When HK-2 cells were cultured under 1% oxygen for 24 h, then switched to 21% oxygen for 24 h (hypoxia-reoxygenation), acrolein accumulated and SMOX mRNA and protein levels were increased. Acrolein induced cell death and fibrosis-related TGFB1 mRNA in HK-2 cells. Administration of the acrolein scavenger cysteamine suppressed the acrolein-induced upregulation of TGFB1 mRNA. Cysteamine also inhibited a decrease in the mitochondrial membrane potential observed by MitoTrackerCMXRos, and cell death induced by hypoxia-reoxygenation. The siRNA-mediated knockdown of SMOX also suppressed hypoxia-reoxygenation-induced acrolein accumulation and cell death. Our study suggests that acrolein exacerbates acute kidney injury by promoting tubular cell death during ischemia-reperfusion injury. Treatment to control the accumulation of acrolein might be an effective therapeutic option for renal ischemia-reperfusion injury.

DOI： 10.1016/j.bbrc.2023.05.029

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(株)東京医学社  

57歳男性。糖尿病性腎症による末期腎不全のため腹膜透析(PD)が導入されていた。今回、排液混濁と腹痛を主訴に受診し、排液所見よりPD関連腹膜炎と診断され、治療としてバンコマイシン、セフタジジムの腹腔内投与が行われた。その後、第3病日よりリファンピシンを併用したが、第7病日に腹水培養からKocuria rhizophilaが検出され、第8病日よりはアンピシリン、スルバクタムに変更した。しかし、治癒には至らず、第20病日にPDカテーテルを抜去後、セファゾリンの経静脈投与に変更した。その結果、腹痛や排液混濁は改善し、第33病日にPDカテーテルの再留置が行われ、第46病日に退院となった。

Language：Japanese