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

BACKGROUND: Cisplatin (CP), a platinum-based chemotherapeutic agent, is widely used to treat cancer but causes nephrotoxicity. Riociguat, a soluble guanylate cyclase (sGC) stimulator that enhances the nitric oxide-sGC-cGMP signaling pathway, was investigated for its potential protective effects against cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: Rats were randomly divided into four equal groups (six rats each) and treated for nine consecutive days. The first and second groups were given oral carboxymethylcellulose 0.5% (vehicle) for 9 days, and on day 6 were injected intraperitoneally with saline or CP, respectively. The third and fourth groups were treated orally with two doses of riociguat (3 and 10 mg/kg/day) for 9 days, and received intraperitoneal injections of CP on day 6. Blood, urine, and kidney tissues were analyzed 24 h after the last treatment. RESULTS: CP significantly elevated the markers of kidney function, including uric acid, serum creatinine, and urea. CP also caused histological kidney damage. Antioxidant markers, including catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), and total antioxidant capacity (TAC) were significantly reduced, while inflammatory cytokines (IL-1β, IL-6, and TNF-α) and lipid peroxidation (MDA) were markedly increased. Riociguat improved kidney structure and significantly reduced kidney function markers, MDA, and inflammatory cytokines while restoring GR, TAC, SOD, and CAT activities. CONCLUSIONS: These results indicate that riociguat exerts protection of the kidneys from CP-caused kidney damage by antioxidation and anti-inflammation. Riociguat may have potential as an adjunct therapy to mitigate CP-associated nephrotoxicity.