In sepsis-associated cardiotoxicity, remifentanil reduces oxidative stress, inflammation, and apoptosis to maintain mitochondrial biogenesis by inhibiting NFkB and cas-3 immunoexpressions and enhancing SIRT1 upregulation

Objective: Sepsis-induced cardiotoxicity (SIC) is a critical complication characterized by inflammation, oxidative stress, and apoptosis, leading to myocardial dysfunction. The short-acting opioid analgesic remifentanil (REMI) possesses antioxidant and anti-inflammatory properties. This study aimed to evaluate the cardioprotective effects of REMI on lipopolysaccharide (LPS)-induced SIC by examining inflammation, oxidative stress, apoptosis, and mitochondrial function. Materials and methods: Thirty-two female Wistar albino rats were divided into four groups: control, lipopolysaccharide (LPS), LPS+REMI, and REMI. Myocardial and aortic tissues were analyzed for histopathology, immunoexpression of Caspase-3 (Cas-3), nuclear factor kappa beta (NF-κB), and tumor necrosis factor alpha (TNF-α). Oxidative stress markers, including total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), were measured. Mitochondrial apoptosis-related gene expression of AMP-activated protein kinase (AMPK), BCL2 Associated X (BAX), B-cell lymphoma 2 (BCL-2), Sirtuin 1 (SIRT1), and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) was assessed. Results: LPS administration induced severe histopathological damage, increased oxidative stress (elevated TOS and OSI), and upregulated apoptotic (Cas-3, BAX/BCL-2 imbalance) and inflammatory (NF-κB, TNF-α) markers. REMI treatment significantly alleviated myocardial and aortic injury, reducing the histopathological score. It markedly decreased Cas-3, NF-κB, and TNF-α expression, lowered TOS and OSI levels, and modulated the BAX/BCL-2. Furthermore, REMI restored the expression of AMPK, SIRT1, and PGC-1α genes, indicating a protective effect on mitochondrial biogenesis and energy metabolism. Conclusions: REMI exhibits significant cardioprotective effects in LPS-induced SIC by attenuating inflammation, oxidative stress, and apoptosis while preserving mitochondrial homeostasis.