Endoplasmic reticulum stress promotes oxidative stress: A novel mechanism of citrinin-induced thymus and spleen injury

Abstract

Citrinin (CTN) is a mycotoxin that is widespread and can contaminate a wide range of food products, posing a threat to human and animal health. The spleen and thymus are important immune organs of the body, and the damaging effects of CTN on immune organs and their mechanism are still unclear. In this study, we induced spleen and thymus injury in mice by exposure to different doses of CTN (0, 1.25, 5, or 20 mg/kg) and preliminarily investigated the damage mechanisms. It was observed that CTN exposure caused immune damage to the thymus and spleen, which are immune organs in mice. In addition, CTN exposure decreased the content of glutathione (GSH), an antioxidant, and the activities of antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT); it also increased the levels of oxidized products such as reactive oxygen species (ROS)and malondialdehyde (MDA). These results suggested that CTN induced oxidative stress in the thymus and spleen. The present study also found that CTN exposure significantly increased the expression of endoplasmic reticulum (ER) stress signature proteins, including C/EBP homologous protein (CHOP) and glucose-regulated protein 78(GRP78). Notably, pretreatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 240 mg/kg, intraperitoneally) attenuated CTN-induced oxidative stress in the spleen and thymus of mice and partially alleviated histopathological damage, demonstrating that inhibition of ER stress may be a novel strategy to prevent or treat CTN-induced immune organ damage.