Comparative Effects of Fedratinib and Upadacitinib on Renal Ischemia-Reperfusion Injury in Rat Models

Abstract

Renal ischemia-reperfusion injury (RIRI) is a severe condition that frequently occurs following kidney transplantation or surgical procedures affecting renal blood flow. Inflammatory responses, oxidative stress, and apoptotic pathways significantly contribute to RIRI. This study aimed to compare the renoprotective effects of Fedratinib, a JAK2 inhibitor, and Upadacitinib, a JAK1 inhibitor, in rat models of RIRI. Both inhibitors were administered one hour prior to ischemia induction, and the effects on renal function, inflammation, and cell death pathways were assessed. The findings revealed that both Fedratinib and Upadacitinib significantly reduced serum creatinine and urea levels, inflammatory cytokines (TNF-α, IL-6), and markers of apoptosis (BCL2/BAX) by suppressing the JAK/STAT signaling pathways. Histopathological analysis showed substantial reduction in renal tissue damage in the treated groups compared to controls. The study concludes that JAK inhibition by either drug provides significant renoprotection in RIRI, though with some differences in the degree of pathway inhibition and clinical implications.