Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) in transplantation and major surgery, with limited effective pharmacological interventions. This study evaluated the prophylactic effect of desloratadine, a second-generation H1-receptor antagonist with anti-inflammatory and antioxidant properties, on renal IRI. Twenty-one male Sprague–Dawley rats were randomly assigned to three groups (n = 7 each): Sham, I/R (45 min ischemia followed by 24 h reperfusion), and I/R + desloratadine (5 mg/kg, orally, 1 h prior to ischemia). After 24 h of reperfusion, renal function, oxidative stress markers, histopathology, and antioxidant gene expression were assessed. I/R significantly impaired renal function (increased plasma creatinine and urea, decreased creatinine clearance; P < 0.001), reduced effective free-water reabsorption, and increased oxidative stress (elevated TOS, reduced TAC and GSH; P < 0.01–0.001). Desloratadine significantly improved renal function, restored tubular concentrating ability, reduced oxidative stress, and increased GSH levels ( P < 0.05–0.001 vs. I/R). At the molecular level, I/R upregulated Nrf2 and HO-1 expression but downregulated Gclc and Gclm, while desloratadine further enhanced Nrf2/HO-1 expression and restored Gclc/Gclm levels. Histological analysis confirmed attenuation of tubular injury. In conclusion, desloratadine pretreatment is associated with protection against renal IRI, potentially through modulation of the Nrf2–GCL–GSH antioxidant pathway and preservation of tubular function. These findings support its potential repurposing as an adjuvant strategy in settings at risk of renal ischemic injury. • Bilateral renal artery occlusion (45 min) followed by 24 h reperfusion in Sprague-Dawley rats induced significant tubular dysfunction, reduced water reabsorption, oxidative stress, and GSH depletion. • Pretreatment with desloratadine (5 mg/kg, gavage) markedly improved renal function and attenuated histological damage. • Desloratadine restored reduced glutathione (GSH) levels and decreased markers of oxidative injury. • Desloratadine enhanced expression of Gclc and Gclm , promoting glutathione synthesis, and further upregulated Nrf2 and HO-1 , reinforcing antioxidant defenses. • Preservation of effective free water reabsorption (effTcH 2 O) indicates protection of tubular concentrating ability. • Desloratadine exerts renoprotective effects through activation of the Nrf2–GCL–GSH pathway , reducing oxidative stress and maintaining renal tubular function. These results suggest potential clinical application of desloratadine in settings of renal ischemia, including transplantation and surgery.
Gholampour et al. (Wed,) studied this question.