Abstract
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.