Targeting ferroptosis as a prospective therapeutic approach for diabetic nephropathy

Figures & data

Figure 1. In diabetic nephropathy, high glucose stimulates ferroptosis in kidney cells including tubular epithelial cells, podocytes, glomerular endothelial cells, and mesangial cells.

Figure 2. Overview of the ferroptosis mechanism. Primary regulatory pathways of ferroptosis might be summarized as the influence of lipid metabolism, ROS accumulation, and iron metabolism. GSH, glutathione; GPX4, glutathione peroxidase 4; LIP, labile iron pool; Nrf2, nuclear-factor- erythroid2-related factor 2; TRF, transferrin; LPO, lipid peroxide; H2O2, hydrogen peroxide; · OH, producing toxic hydroxyl radicals; Fe2+, divalent iron ionization; PUFAs, polyunsaturated fatty acids; ROS, reactive oxygen species; Cys, cystine; Glu, glutamate; PRMT4, Protein Arginine Methyltransferase 4; KLF2, Kruppel-like factor 2; This figure is created with BioRender.com.

Table 1. Drugs targeting ferroptosis in DN.

Drugs	Samples	Targets	Induce or inhibit ferroptosis	References
Vitexin	Cell: HK-2 cells Animal: STZ-induced diabetic rats	GPX4, SCL7A11	inhibit	[66]
2-Deoxy-D-ribose (dRib)	Cell: Primary culture of RTECs, NRK-52E cells	GPX4, SCL7A11, ACSL4 CHAC1, Nrf2	induce	[68]
San-Huang-Yi-Shencapsule (SHYS)	Animal: STZ-induced diabetic mice	Cystine, GPX4	inhibit	[64]
Glabridin	Cell: NRK-52E cells Animal: STZ-induced diabetic rats	GPX4, SLC7A11, SLC3A2, VEGF, Akt, ERK	inhibit	[53]
Platycodin D	Cell: HK-2 cells	FTH-1, SLC7A11, GPX4, ACSL4, TFR1	inhibit	[48]
Dapagliflozin (DAPA),	Cell: HK-2 cells Animal: STZ-induced diabetic mice	SLC40A1, GPX4, SLC7A11	inhibit	[51]
Schisandrin A	Cell: Human renal glomerular endothelial cells (HRGECs) Animal: STZ-induced diabetic mice	TNF-α, INF-γ, GPX4,TXNIP,NLRP3,Nrf2, HO-1, AdipoR1/ AMPK	inhibit	[62]
quercetin (QCT)	Cell: Human renal glomerular endothelial cells (HRGECs) Animal: db/db mice	GPX4, SLC7A11, TFR1, FTH1	inhibit	[67]
Empagliflozin	Cell: HK-2 cells Animal: STZ-induced diabetic mice	AMPK, NRF2, GPX4, SLC7A11	inhibit	[43]
Mangiferin monosodium salt (MGM)	Animal: STZ-induced diabetic rats	phosphorylated insulin receptor substrate 1(Tyr608), CoQ10, MVA, AA, GPX4	inhibit	[60]
aspirin	Cell: HK-2 cells Animal: STZ-induced diabetic mice	COX-2, GPX4,	inhibit	[54]
Calycosin	Cell: HK-2 cells	GPX4	inhibit	[55]
NAC	Cell: Madin-darby canine kidney (MDCK) cells (a dog renal tubular epithelial cell line) Animal: STZ-induced Beagle	TXNIP, SIRT3, SLC7A11, HMGB1, CD71	inhibit	[49]

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Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.