Nebivolol protects the liver against lipopolysaccharide-induced oxidative stress, inflammation, and endoplasmic reticulum–related apoptosis through Chop and Bip/GRP78 signaling

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2024-08, Vol.397 (8), p.5899-5907
• Main Authors: Unal, Onur, Erzurumlu, Yalcin, Asci, Halil, Gunduru Acar, Berivan, Bedir, Mehmet, Ozmen, Ozlem
• Format: Article
• Language: English
• Subjects: Alanine transaminase; Animals; Apoptosis; Apoptosis - drug effects; Aspartate transaminase; Biomedical and Life Sciences; Biomedicine; Caspase-3; CCAAT/enhancer-binding protein; Endoplasmic reticulum; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress - drug effects; Gene expression; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Hemorrhage; Hyperemia; IL-1β; Immunohistochemistry; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Inflammation - prevention & control; Interleukin 1; Interleukin-1beta - metabolism; Lipopolysaccharides; Lipopolysaccharides - toxicity; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Nebivolol - pharmacology; Nebivolol - therapeutic use; Neurosciences; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Pharmacology/Toxicology; Proteins; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sepsis; Signal Transduction - drug effects; Transcription Factor CHOP - genetics; Transcription Factor CHOP - metabolism
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-024-02990-3

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