Article 2023 · 12 atıf

Blockade of P2X7 receptor-mediated purinergic signaling with A438079 protects against LPS-induced liver injury in rats

Özet

The study aimed to investigate the hepatoprotective effects of purinergic receptor (P2X7R) antagonism by A438079 in liver damage. An experimental model of inflammation was performed by intraperitoneal (i.p.) lipopolysaccharide (LPS) administration in the rat. The groups were Control, A438079, dimethyl sulfoxide (DMSO), LPS, LPS + DMSO, and LPS + A438079. Following LPS (8 mg/kg) injection, A438079 (15 mg/kg) and DMSO (0.1 mL) were administrated (i.p) in the study groups. The blood and the liver tissues were removed for histological, biochemical, and western blot analyses. In the biochemical analysis, serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, the tissue glutathione (GSH) level, and superoxide dismutase (SOD) activity dramatically decreased and malondialdehyde (MDA) level increased in the LPS and LPS + DMSO groups compared to the LPS + A438079 group. In the histological analysis, severe sinusoidal dilatation, necrotic hepatocytes, and inflammatory cell infiltration were observed in the LPS and LPS + DMSO groups while these effects were lessened in the LPS + A438079 group. The relative protein expression levels of P2X7R, Nf-kB-p65, IL-6, and Caspase-3 were significantly higher in the LPS and the LPS + DMSO groups than in the LPS + A438079 group. On the other hand, these protein expressions were considerably lower in the Control, A438079, and DMSO groups compared to the LPS + A438079 group. In addition, Bcl-2 protein expression was significantly lower in the LPS and the LPS + DMSO groups and higher in the LPS + A438079 group compared to the other groups. The protective effect of A438079 against LPS-induced hepatic inflammation may be related to P2X7R antagonism, inflammatory mediators, and apoptotic cell death.

Anahtar Kelimeler

A438079 cell death inflammation LPS rat liver CELLS ACID HEPATOTOXICITY INFLAMMATION RESVERATROL EXPRESSION IL-1-BETA MELATONIN RELEASE ASSAY

WoS Kategorileri

Biochemistry & Molecular Biology Toxicology

Sürdürülebilir Kalkınma Amaçları

Sağlık ve Kaliteli Yaşam

Künye

Dergi: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
Yıl: 2023
Cilt: 37
Sayı: 10
ISSN: 1095-6670
eISSN: 1099-0461
DOI: 10.1002/jbt.23443
WoS UID: WOS:001016411600001

Yayını aç (DOI)