Ojeoksan Ameliorates Cisplatin-Induced Acute Kidney Injury in Mice by Downregulating MAPK and NF-κB Pathways

Area of Science:

• Pharmacology
• Nephrology
• Herbal Medicine

Background:

• Cisplatin is a vital anticancer drug but causes significant kidney damage (nephrotoxicity).
• Developing effective treatments to prevent cisplatin-induced acute kidney injury (AKI) is crucial for cancer therapy.
• Ojeoksan (OJS), a traditional Korean herbal prescription, has not been previously studied for its effects on cisplatin-induced AKI.

Purpose of the Study:

• To investigate the potential reno-protective effects of Ojeoksan (OJS) against cisplatin-induced acute kidney injury (AKI) in a mouse model.
• To evaluate the impact of OJS on kidney function markers and histological damage following cisplatin administration.
• To explore the molecular mechanisms underlying OJS's protective effects, focusing on inflammatory and signaling pathways.

Main Methods:

• Mice were administered varying doses of OJS (50, 100, 200 mg/kg) orally one hour before cisplatin injection (20 mg/kg).
• Kidney function was assessed by measuring blood urea nitrogen (BUN) and serum creatinine (SCr) levels.
• Kidney tissue histology was examined for damage, and levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified.
• The involvement of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways was investigated.

Main Results:

• OJS administration significantly inhibited the cisplatin-induced increase in BUN and SCr levels.
• OJS treatment reduced kidney histological damage, including loss of brush borders, renal tubular necrosis, and cast formation.
• OJS decreased the levels of pro-inflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α.
• OJS effectively inhibited the activation of the MAPK and NF-κB signaling pathways in cisplatin-induced AKI.

Conclusions:

• Ojeoksan (OJS) demonstrates significant reno-protective effects against cisplatin-induced acute kidney injury (AKI).
• OJS mitigates kidney damage and inflammation by downregulating the MAPK and NF-κB pathways.
• OJS represents a promising therapeutic candidate for preventing or treating cisplatin-induced nephrotoxicity.