Shenkang Injection Prevents Contrast-Induced Nephropathy by Regulating Ferroptosis Via the STAT3/HIF-1α/HMOX-1...

Area of Science:

• Nephrology
• Pharmacology
• Molecular Biology

Background:

• Contrast Medium (CM) administration can lead to Contrast-Induced Nephropathy (CIN), a significant cause of acute kidney injury.
• Effective treatments for CIN are limited, and its underlying pathological mechanisms remain unclear.

Purpose of the Study:

• To investigate the therapeutic potential of SKI against CIN.
• To elucidate the molecular mechanisms by which SKI exerts its protective effects on the kidneys.

Main Methods:

• Network pharmacology analysis identified overlapping targets of SKI, CIN, and ferroptosis-related genes.
• Protein-Protein Interaction (PPI) networks and bioinformatics analyses (GO, KEGG) were employed.
• In vitro and in vivo experiments, including molecular docking and biomarker analysis, validated the findings.

Main Results:

• Fifteen ferroptosis-related targets of SKI were identified for CIN prevention, highlighting the HIF-1 signaling pathway.
• Contrast agents induced CIN and ferroptosis in vivo, evidenced by biomarker analysis and electron microscopy.
• SKI and Ferrostatin-1 (Fer-1) treatment suppressed ferroptosis and downregulated STAT3, HIF-1α, and HMOX-1, mitigating CIN.

Conclusions:

• SKI demonstrates therapeutic potential for CIN by inhibiting oxidative stress and ferroptosis.
• The STAT3/HIF-1α/HMOX-1 signaling pathway is a key target for SKI's protective effects against CIN.
• This study provides a basis for developing multi-target therapies for CIN.