The role of fluvoxamine in the treatment of endotoxin-induced acute heart injury
British Journal of Pharmacology, cilt.183, sa.13, ss.3815-3828, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 183 Sayı: 13
- Basım Tarihi: 2026
- Doi Numarası: 10.1111/bph.70453
- Dergi Adı: British Journal of Pharmacology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, CINAHL, EMBASE
- Sayfa Sayıları: ss.3815-3828
- Anahtar Kelimeler: apoptosis, fluvoxamine, inflammation, lipopolysaccharide, oxidative stress
- İstanbul Yeni Yüzyıl Üniversitesi Adresli: Hayır
Özet
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.