Duygu Burcu Arda¹, Ejder Saylav Bora² , Mustafa Agah Tekindal³, Oytun Erba?⁴

Abstract

Purpose: To assess the effect of saroglitazar (a dual-acting peroxisome proliferator-activated receptor alpha (PPAR-α/γ) agonist in sepsis-induced acute kidney injury (S-AKI) using a rat model. Methods: Female Wistar albino rats were divided into control (n = 12), and study group (n = 24; further divided into groups 1 and 2; n = 12 each) following cecal ligation and puncture (CLP) procedure. Control group received normal saline while study group 1 received normal saline and study group 2 received saroglitazar (2 mg/kg/day) intraperitoneally (IP) twice daily for 5 days. Biochemical markers (malondialdehyde (MDA), neutrophil extracellular traps (NETs), insulin-like growth factor (IGF) binding protein 7 (IGFBP-7), blood urea nitrogen (BUN), creatinine, and nod-like receptor protein 3 (NLRP3), neurolopin-1), histopathology of kidney, as well as enzyme-linked immunosorbent assay (ELISA) were employed to evaluate renal injury and therapeutic effects. Results: Saroglitazar significantly reduced MDA, TNF-α, NETs, IGFBP-7, BUN, creatinine, NLRP3 and neuropilin-1 (p < 0.05) compared to control group. Histopathological analysis revealed significantly reduced tubular injury and inflammation in the study group compared to control group (p < 0.01) Conclusion: Saroglitazar demonstrates protective and therapeutic effects against S-AKI in rats by reducing inflammation, oxidative stress, and cellular damage. Early saroglitazar use in septic patients may be beneficial, and further clinical studies are warranted to establish its efficacy and safety in managing S-AKI.