Exploring the renoprotective effects of umbelliferone in rats subjected to ischemia/reperfusion injury

Abstract

Objective(s): Renal ischemia/reperfusion (IR) injury is a major cause of acute kidney injury, driven by oxidative stress, inflammation, and apoptosis. This study investigated the dose-dependent renoprotective effects of umbelliferone, a coumarin derivative, in a rat model of renal IR injury. Materials and Methods: Thirty female Wistar rats were randomly assigned to five groups (n=6): Control, Sham, IR, IR+U50 mg/kg, and IR+U100 mg/kg. Serum cytokines (TNF-α, IL-1β, IL-6, IL-10, IL-15, IL-18, TGF-β) were measured by ELISA; renal oxidative stress markers (MDA, GSH, NO) by biochemical assays; NF-κB by immunohistochemistry; and Bax, Bcl-2, NF-κB, NRF2, P2X7, and TNF-α gene expression by RT-qPCR. Results: IR injury significantly increased pro-inflammatory cytokines, including IL-6 (15.03→25.11 ng/mL), TNF-α (55.63→70.62 ng/l), and IL-1β; elevated MDA (1.90→9.64 nmol/g) and NO (4.02→8.58 µM); and depleted GSH (9.81→1.86 nmol/g)(all P<0.001). Renal Bax, NF-κB, P2X7, and TNF-α expression and NF-κB immunoreactivity were increased, whereas NRF2 was decreased (P<0.001). Umbelliferone, particularly at 100 mg/kg, significantly reversed these changes, lowering IL-6 (15.12 ng/ml), TNF-α (57.55 ng/l), MDA (3.21 nmol/g), and NO (4.45 µM), restoring GSH (4.27 nmol/g) (P<0.001 vs IR), attenuating Bax, NF-κB, P2X7, and TNF-α expression, and partially restoring NRF2. Conclusion: In this preclinical model, umbelliferone was associated with dose-dependent renoprotective effects against acute renal IR injury, attenuating oxidative stress, inflammation, and apoptosis. Further functional and mechanistic studies are needed before its therapeutic potential can be established.