Salvianolic Acid B Attenuates Ferroptosis in Acute Kidney Injury by Targeting PRDX5

Area of Science:

• Nephrology
• Biochemistry
• Pharmacology

Background:

• Acute kidney injury (AKI) is a frequent complication of cisplatin chemotherapy.
• Ferroptosis, a regulated form of cell death, is the primary mechanism of renal tubular epithelial cell death in AKI.
• Salvianolic acid B (SAB), a natural compound, possesses anti-inflammatory and antioxidant properties, but its role in AKI-related ferroptosis is unclear.

Purpose of the Study:

• To investigate the protective effects of Salvianolic acid B (SAB) against acute kidney injury (AKI).
• To elucidate the underlying mechanisms of SAB's action, focusing on ferroptosis in renal tubular epithelial cells.

Main Methods:

• Cisplatin- and folic acid-induced AKI models in vivo and in vitro (HK-2 cells).
• Assessment of ferroptosis markers and renal function.
• Online target prediction, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and molecular docking to identify and validate SAB's molecular target.
• PRDX5 gene silencing to confirm its role in SAB's protective effect.

Main Results:

• SAB treatment alleviated renal dysfunction in AKI models and protected HK-2 cells from cisplatin-induced injury.
• SAB was found to target and bind to PRDX5, enhancing its redox activity.
• This enhancement of PRDX5 activity potentiated the inhibitory effects of SLC7A11 and GPX4 on ferroptosis.
• Silencing PRDX5 partially reversed the protective effects of SAB, confirming PRDX5 as a key mediator.

Conclusions:

• Salvianolic acid B (SAB) demonstrates significant renoprotective effects against AKI induced by cisplatin and folic acid.
• SAB exerts its protective action by targeting PRDX5, modulating its redox activity to inhibit ferroptosis in renal tubular epithelial cells.
• These findings highlight SAB as a potential therapeutic agent for treating AKI, particularly that associated with chemotherapy.