Nebivolol protects the liver against lipopolysaccharide-induced oxidative stress, inflammation, and endoplasmic reticulum–related apoptosis through Chop and Bip/GRP78 signaling
Naunyn-Schmiedeberg's Archives of Pharmacology, cilt.397, sa.8, ss.5899-5907, 2024 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 397 Sayı: 8
- Basım Tarihi: 2024
- Doi Numarası: 10.1007/s00210-024-02990-3
- Dergi Adı: Naunyn-Schmiedeberg's Archives of Pharmacology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Veterinary Science Database
- Sayfa Sayıları: ss.5899-5907
- Anahtar Kelimeler: Bip, Chop, Endoplasmic reticulum stress, Inflammation, Liver, Nebivolol
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
This study aimed to examine the protective role of nebivolol (NEB) on liver tissue against the lipopolysaccharide (LPS)-induced sepsis model in rats by targeting endoplasmic reticulum (ER) stress–related binding immunoglobulin protein (Bip), CCAAT-enhancer-binding protein homologous protein (Chop) signaling pathways. Four groups, each comprising eight rats, were established: control, LPS, LPS + NEB, and NEB. Biochemical analyses included total oxidant status (TOS), serum aspartate transaminase (AST), and alanine aminotransferase (ALT) levels. Additionally, genetic assessments involved Chop and Bip/GRP78 mRNA expression levels, while histopathological examinations were conducted. Immunohistochemistry was used to determine interleukin-1 beta (IL-1 β) and caspase-3 levels. The LPS group exhibited significantly higher AST, ALT, oxidative stress index, and TOS levels compared to the control group. Moreover, the LPS group demonstrated markedly increased Chop and Bip/GRP78 mRNA expression compared to the control group. Immunohistochemical analysis of the LPS group revealed significant upregulation in IL-1β and caspase-3 expressions compared to the control group. Additionally, the LPS group showed significant hyperemia, mild hemorrhage, and inflammatory cell infiltrations. Comparatively, the LPS+NEB group exhibited a reversal of these alterations when compared to the LPS group. Collectively, our findings, suggest that NEB holds promise as a treatment in conditions where oxidative damage, inflammation, and ER stress–related apoptosis play significant roles in the pathogenesis. Graphical abstract: (Figure presented.)