Thiolutin attenuates ischemic stroke injury via inhibition of NLRP3 inflammasome: an in vitro and in vivo study

Exp Brain Res. 2023 Feb 7. doi: 10.1007/s00221-023-06566-0. Online ahead of print.ABSTRACTA recent study confirmed that thiolutin is effective in the treatment of nucleotide-binding domain-like receptor protein 3 (NLRP3)-related inflammatory diseases. Nevertheless, whether thiolutin (THL) is involved in the regulation of NLRP3 inflammasome in ischemic stroke is not known. The murine neuronal cell oxygen-glucose deprivation (OGD) model was first established, and then different concentrations (25 nM and 50 nM) of THL were administered for 48 h incubation, respectively. Subsequently, cell viability and toxicity, and the levels of intracellular inflammatory factors interleukin-1β (IL-1β), interleukin-18 (IL-18), oxidative stress factors superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA), and NLRP3 inflammasome activation-related proteins pro-caspase, caspase-1, apoptosis-associated speck like-protein (ASC) and NLRP3 were examined, respectively. We further established the mouse middle cerebral artery occlusion (MCAO) model to evaluate the therapeutic effects of THL on cerebral infarction like behaviors in mice and the preventive effects on NLRP3 inflammasome activation in vivo. Cell cytotoxic, and the levels of inflammatory factors and oxidative stress were conspicuously increased, and NLRP3 inflammasome was materially activated in the OGD-induced cell model and MCAO-established mouse model, which were partially countered by THL...
Source: Cell Research - Category: Cytology Authors: Source Type: research