Silybin Improves Acute Kidney Injury by Regulating HDAC6/NF-κB/NLRP3 Signaling to Reduce Inflammation and Ferroptosis

Area of Science:

• Nephrology
• Molecular Biology
• Pharmacology

Background:

• Inflammation and ferroptosis are key contributors to cisplatin (CP)-induced acute kidney injury (AKI).
• Silybin (SYB), a natural flavonoid, exhibits renal protective properties, but its precise mechanisms in AKI are not fully understood.

Purpose of the Study:

• To investigate the protective mechanisms of Silybin (SYB) against cisplatin (CP)-induced acute kidney injury (AKI) in cellular and animal models.
• To elucidate the role of the HDAC6/NF-κB/NLRP3 pathway in SYB's renoprotective effects.

Main Methods:

• Utilized HK-2 cell and mouse models of CP-induced AKI.
• Assessed cell viability, apoptosis, oxidative stress, and ferroptosis markers.
• Measured renal function (serum creatinine, urea nitrogen) and performed histological analysis.
• Employed Western blotting to analyze protein expression, including HDAC6, NF-κB, NLRP3, and ferroptosis-related proteins.

Main Results:

• SYB treatment improved cell viability and proliferation while reducing apoptosis, oxidative stress, and ferroptosis in CP-treated HK-2 cells.
• In vivo, SYB administration significantly decreased serum creatinine, urea nitrogen, and inflammatory cytokine levels, ameliorating renal tissue damage.
• SYB downregulated HDAC6 expression, inhibited NF-κB/NLRP3 activation, and suppressed ferroptosis, with HDAC6 overexpression reversing these protective effects.

Conclusions:

• Silybin (SYB) effectively mitigates cisplatin-induced acute kidney injury (AKI).
• SYB exerts its renoprotective effects by suppressing inflammation and ferroptosis through the modulation of the HDAC6/NF-κB/NLRP3 signaling pathway.
• Targeting the HDAC6/NF-κB/NLRP3 axis represents a promising therapeutic avenue for managing AKI.