1. Academic Validation
  2. Empagliflozin improves kidney senescence induced by D-galactose by reducing sirt1-mediated oxidative stress

Empagliflozin improves kidney senescence induced by D-galactose by reducing sirt1-mediated oxidative stress

  • Biogerontology. 2023 May 25. doi: 10.1007/s10522-023-10038-x.
Ronghua Fang 1 Jie Chen 1 2 Jiangchuan Long 1 Binghan Zhang 1 3 Qixuan Huang 1 Shengbing Li 1 Ke Li 1 Qing Chen 1 Dongfang Liu 4
Affiliations

Affiliations

  • 1 Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • 2 Department of Endocrinology, The Ninth People's Hospital of Chongqing, Chongqing, 400700, China.
  • 3 Department of Endocrinology, Chongqing General Hospital, Chongqing, 401147, China.
  • 4 Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. ldf023023@qq.com.
Abstract

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have received widespread attention because of their significant protective effects on the kidney. Previous studies have shown that SIRT1, as which is an antiaging protein, is closely related to the maintenance of redox homeostasis. The goal of this study was to determine whether empagliflozin could ameliorate D-galactose-induced renal senescence in mice, and examine the possible mechanisms of SIRT1. We constructed a rapid ageing model in mice by administering D-galactose. An ageing model was constructed by treating cells with high glucose. Treadmill and Y-maze tests were used to assess exercise tolerance and learning memory ability. Pathologically stained sections were used to assess kidney injury. Tissue and cell senescence were evaluated by senescence-associated β-galactosidase staining. The expression levels of P16, SOD1, SOD2 and SIRT1 were detected by immunoblotting. D-gal-treated mice exhibited significant age-related changes, as measured by behavioural tests and ageing marker protein levels. empagliflozin alleviated these ageing manifestations. In addition, SIRT1, SOD1 and SOD2 levels were downregulated in model mice and upregulated by empagliflozin treatment. Empagliflozin had similar protective effects at the cellular level, and these effects were reduced by the SIRT1 Inhibitor. Empagliflozin has an antiaging effect, which may be related to reducing Sirt1-mediated oxidative stress.

Keywords

Ageing; D-galactose; Empagliflozin; Kidney; Redox signalling; Sirt1.

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