Tirzepatide Protects the Kidney by Modulating Oxidative Stress, Inflammation, and Apoptosis in an Induced Ischemia-Reperfusion Rat Model

Renal ischemia-reperfusion (I/R) injury is major cause of acute kidney injury (AKI), driven by oxidative stress, inflammation, and cell death, and no effective pharmacological therapy available. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown metabolic and anti-inflammatory benefits that may offer renal protection. This study investigate its effect against acute renal I/R injury in rats. Twenty-four male Sprague-Dawley rats were assigned to four groups: sham, I/R control, I/R + DMSO, and I/R + tirzepatide (1.35 mg/kg). Drug or vehicle was administered 24 hours and 1 hour before 40 minutes of bilateral renal ischemia followed by 2 hours of reperfusion. I/R markedly increased serum urea, creatinine, NGAL, oxidative stress markers, TNF-α, caspase-3, and tubular injury. Tirzepatide significantly improved renal function, reduced NGAL, oxidative stress, inflammation, apoptosis, with histological damage. These findings indicate strong renoprotective effect of tirzepatide, that support its potential as a therapeutic option for AKI associated with ischemic insults.