ABSTRACT
Cadmium (Cd) is a transition metal ion that is extremely harmful to human and animal biological systems. Cd is a toxic substance that can accumulate in the food chain and cause various health issues. Sulforaphane (SFN) is a natural bioactive compound with potent antioxidant properties. In our study, 80 1 day-old chicks were fed with Cd (140 mg/kg BW/day) and/or SFN (50 mg/kg BW/day) for 90 days. The blood-thymus barrier (BTB) is a selective barrier separating T-lymphocytes from blood and cortical capillaries in the thymus cortex. Our research revealed that Cd could destroy the BTB by downregulating Wnt/ß-catenin signaling and induce immunodeficiency, leading to irreversible injury to the immune system. The study emphasizes the health benefits of SFN in the thymus. SFN could ameliorate Cd-triggered BTB dysfunction and pyroptosis in the thymus tissues. SFN modulated the PI3K/AKT/FOXO1 axis, improving the level of claudin-5 (CLDN5) in the thymus to alleviate BTB breakdown. Our findings indicated the toxic impact of Cd on thymus, and BTB could be the specific target of Cd toxicity. The finding also provides evidence for the role of SFN in maintaining thymic homeostasis for Cd-related health issues.
Subject(s)
Cadmium , Chickens , Isothiocyanates , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Sulfoxides , Thymus Gland , Animals , Isothiocyanates/pharmacology , Cadmium/toxicity , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Thymus Gland/drug effects , Thymus Gland/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Forkhead Box Protein O1/metabolism , Forkhead Box Protein O1/genetics , Signal Transduction/drug effects , Humans , MaleABSTRACT
The intensive adoption of atrazine (ATZ) is a source of a persistently widespread pollutant in daily life. However, ATZ is still used as an essential herbicide in numerous countries because its toxic effect is not addressed as a public health concern. This study found that ATZ exposure caused mitophagy and pyroptosis crosstalk in the thymus. And it could destroy the thymus architecture, inducing immunodeficiency. Lycopene (LYC), a natural bioactive component, is applied to reduce the risk of chronic diseases caused by environmental factors. This work also investigated the health benefits of LYC in the ATZ-induced toxic effect on the thymus. LYC could ameliorate the ATZ-induced mitophagy and pyroptosis. LYC modulated the IL-6/STAT3/Foxo1 axis, improving the level of CD45 in the thymus. This work sheds light on the toxic effect of ATZ on the thymus, and it will provide evidence for ATZ health risks. Additionally, the finding also underscores a novel target of LYC in maintaining thymic homeostasis in ATZ exposure.