Riociguat Alleviates Cisplatin-Caused Kidney Injury by Suppressing Oxidative Stress and Inflammation

Area of Science:

• Pharmacology
• Nephrology
• Oncology

Background:

• Cisplatin (CP) is a vital chemotherapy drug but induces significant nephrotoxicity.
• Riociguat, a stimulator of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway, was evaluated for renoprotective potential.

Purpose of the Study:

• To investigate the protective effects of riociguat against cisplatin-induced nephrotoxicity in a rat model.
• To assess the impact of riociguat on kidney function, oxidative stress, and inflammation markers following cisplatin exposure.

Main Methods:

• Rats received daily oral administration of vehicle or riociguat (3 and 10 mg/kg/day) for nine days.
• Cisplatin was administered intraperitoneally on day 6, with analyses conducted 24 hours post-treatment.
• Kidney function markers, histological damage, antioxidant status, lipid peroxidation, and inflammatory cytokines were assessed.

Main Results:

• Cisplatin significantly increased kidney function markers (uric acid, creatinine, urea) and caused histological damage.
• Cisplatin reduced antioxidant markers (CAT, GR, SOD, TAC) and increased inflammatory cytokines (IL-1β, IL-6, TNF-α) and lipid peroxidation (MDA).
• Riociguat treatment notably improved kidney structure, reduced kidney dysfunction markers, MDA, and inflammation, while restoring antioxidant enzyme activities.

Conclusions:

• Riociguat demonstrates significant renoprotective effects against cisplatin-induced nephrotoxicity.
• The protective mechanisms involve potent antioxidation and anti-inflammatory actions.
• Riociguat shows promise as an adjunct therapy to mitigate cisplatin-associated kidney damage.