T-2 Toxin Caused Mice Testicular Inflammation Injury via ROS-Mediated NLRP3 Inflammasome Activation

Abstract

T-2 toxin treatment causes male reproduction system dysfunction, although the exact mechanism remains unclear. In this research, male Kunming mice and TM4 cells were treated with varying concentrations of the T-2 toxin for evaluating the adverse effect of T-2 toxin on male reproductive function. MCC950 or NAC was used to block NLRP3 inflammasome activation and eliminate reactive oxygen species (ROS) accumulation in the TM4 cell, respectively. The results showed that: (1) T-2 toxin caused testicular atrophy, destroyed the microstructure and ultrastructure of the testis, and caused sperm deformities; (2) T-2 toxin increased the content and gene expressions of TNF-α and IL-6 and decreased the IL-10 content and gene expression, causing testis and TM4 cell inflammatory injury; (3) T-2 toxin activated NLRP3 inflammasome in the testis and TM4 cells and caused ROS accumulation in the testis; (4) suppressing NLRP3 inflammasome activation using 20 nM MCC950 alleviated the TM4 cell inflammatory damage caused via the T-2 toxin; nevertheless, 20 nM MCC950 did not reduce ROS accumulation in TM4 cells; and (5) NAC relieved the inflammatory damage in TM4 cells by inhibiting NLRP3 inflammasome activation. Taken together, T-2 toxin caused testicular inflammation injury through ROS-mediated NLRP3 inflammasome activation, resulting in male reproductive dysfunction.

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

“…To date, little research has focused on relieving the intestinal toxicity of T-2 toxin. Oxidative stress is the main mechanism underlying T-2 toxin-induced enterotoxicity; hence, alleviating oxidative stress has become a potential means to mitigate/block T-2 toxin-induced intestinal toxicity. , Currently, the main strategy for reducing T-2 toxin enterotoxicity is the use of antioxidant substances or increasing the body’s capacity for antioxidants and lowering oxidative stress. However, the limitations of these strategies include the small number of studies that have investigated T-2 toxin.…”

Regulatory effect of zinc finger protein A20 on rheumatoid arthritis through NLRP3/Caspase-1 signaling axis mediating pyroptosis of HFLS- RA cells

“…One important component of innate immunity is the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing (NLRP3) inflamma-some (6)(7)(8). It can be activated by various endogenous danger signals, such as cellular perforin (9), extracellular ATP (10), reactive oxygen species (ROS) (11,12), as well as other exogenous factors, leading to its inappropriate activation or mutations that are closely related to RA (13)(14)(15)(16), inflammatory bowel disease (17)(18)(19), gout (20)(21)(22) as well as other inflammatory autoimmune diseases. Clinical studies have confirmed that in RA patients, IL-18, IL-1β, Caspase-1 and NLRP3 were positively expressed in synovial coated cells and subsynovial tissues, especially in the cytoplasm of synovial lined cells, macrophages and a few inflammatory cells within the synovial interstitium.…”