The role of fluvoxamine in the treatment of endotoxin‐induced acute heart injury

Abstract Background and Purpose Cardiovascular diseases are among the most common health problems worldwide. Inflammation plays a critical role in the pathogenesis of various heart diseases. Lipopolysaccharides (LPS) trigger inflammatory mechanisms, leading to an inflammatory response. Fluvoxamine (FLV) is a selective serotonin reuptake inhibitor with anti‐inflammatory and antioxidative properties. This study investigated the potential protective effects of FLV on sepsis‐induced cardiac inflammation and injury. Experimental Approach Thirty‐two female Wistar Albino rats were divided into four groups: control, LPS (5 mg·kg −1 intraperitoneally), LPS + FLV, and FLV (50 mg·kg −1 ·day −1 orally for 3 days). Thirty minutes after the final FLV administration, LPS was administered, and animals were killed 6 h later. Cardiac tissues were evaluated by histopathological analysis, immunohistochemical assessment of caspase‐3, TNF‐α, interleukin‐1 beta (IL‐1β), interleukin‐6 receptor (IL‐6R), IL‐10, and NF‐κB; biochemical determination of total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI); and gene expression analysis by real‐time quantitative polymerase chain reaction (RT‐qPCR) of sirtuin‐1 (SIRT‐1), nuclear factor erythroid 2–related factor 2 (NRF‐2), peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α), and p53. Key Results LPS administration significantly increased TOS, OSI, caspase‐3, TNF‐α, IL‐1β, IL‐6R, NF‐κB, and p53, while decreasing IL‐10, SIRT‐1, NRF‐2, and PGC‐1α, accompanied by marked inflammatory and structural cardiac damage. FLV treatment markedly reversed these alterations, attenuating inflammation, oxidative stress, and apoptosis. Conclusion and Implications These findings suggest that FLV may confer cardioprotection against LPS‐induced inflammatory and apoptotic cardiac injury, potentially through modulation of IL‐6R/NF‐κB‐mediated inflammatory signalling and the SIRT‐1–NRF‐2–PGC‐1α axis.