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

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=۶): Control, Sham, IR, IR+U۵۰ mg/kg, and IR+U۱۰۰ mg/kg. Serum cytokines (TNF-α, IL-۱β, IL-۶, IL-۱۰, IL-۱۵, IL-۱۸, TGF-β) were measured by ELISA; renal oxidative stress markers (MDA, GSH, NO) by biochemical assays; NF-κB by immunohistochemistry; and Bax, Bcl-۲, NF-κB, NRF۲, P۲X۷, and TNF-α gene expression by RT-qPCR.Results: IR injury significantly increased pro-inflammatory cytokines, including IL-۶ (۱۵.۰۳→۲۵.۱۱ ng/mL), TNF-α (۵۵.۶۳→۷۰.۶۲ ng/l), and IL-۱β; elevated MDA (۱.۹۰→۹.۶۴ nmol/g) and NO (۴.۰۲→۸.۵۸ µM); and depleted GSH (۹.۸۱→۱.۸۶ nmol/g)(all P<۰.۰۰۱). Renal Bax, NF-κB, P۲X۷, and TNF-α expression and NF-κB immunoreactivity were increased, whereas NRF۲ was decreased (P<۰.۰۰۱). Umbelliferone, particularly at ۱۰۰ mg/kg, significantly reversed these changes, lowering IL-۶ (۱۵.۱۲ ng/ml), TNF-α (۵۷.۵۵ ng/l), MDA (۳.۲۱ nmol/g), and NO (۴.۴۵ µM), restoring GSH (۴.۲۷ nmol/g) (P<۰.۰۰۱ vs IR), attenuating Bax, NF-κB, P۲X۷, and TNF-α expression, and partially restoring NRF۲.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.

کلیدواژه ها:

Acute kidney injury ، Apoptosis ، Inflammation ، Oxidative stress ، Reperfusion injury ، Umbelliferone