Quercetin alleviates cadmium-induced BRL-3A cell apoptosis by inhibiting oxidative stress and the PERK/IRE1α/ATF6 signaling pathway

Abstract

The highly toxic heavy metal cadmium (Cd) can enter the body through biological enrichment. As an essential metabolic organ in the body, the liver is an important target organ of Cd poisoning. Quercetin (Que) is a type of flavonoid that exhibits the pharmacological activities of scavenging free radicals and antioxidation. 4-Phenylbutyrate (4-PBA) can alleviate endoplasmic reticulum stress (ERS) and is frequently considered an inhibitor of ERS. Previous studies have shown that Que can alleviate rat hepatocyte apoptosis caused by Cd; however, the mechanism remains unclear. To explore the specific mechanism of Que that alleviates Cd-induced hepatocyte apoptosis, we established a model of Cd toxicity and Que rescue in BRL-3A cells and used 4-PBA, an ERS inhibitor, as positive control. Cell Counting Kit-8 was employed to measure cell viability. Fluorescence staining was applied to observe cell apoptosis. Flow cytometry was performed to detect reactive oxygen species levels. Real-time quantitative polymerase chain reaction was adopted to detect the messenger RNA expression levels of ERS and apoptosis-related genes. Western blot was used to observe the expression levels of ERS/apoptosis-related proteins. We confirmed that Que could alleviate the apoptosis caused by Cd in BRL-3A cells by inhibiting the PERK/IRE1α/ATF6 ERS signaling pathway. The effects of Que were similar to those of ERS inhibitors.