TMT induces apoptosis and necroptosis in mouse kidneys through oxidative stress-induced activation of the NLRP3 inflammasome

Trimethyltin chloride (TMT) is an organotin heat stabilizer that is widely used in the production of plastics, and has strong toxicity. Here, the effect of trimethyltin chloride on mouse kidneys and its related mechanism were studied by taking TMT mouse with drinking water as a model. Histological examination and TUNEL results showed that the trimethyltin chloride group had typical apoptosis and necroptosis characteristics. Therefore, the level of oxidative stress was detected,and the expression of related genes was verified by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot methods. The results showed that oxidative stress was activated (MDA,SOD,CAT,T-AOC), released ROS, activated NF-kappa B pathway,activated inflammasome (NLRP3, Caspase-1,ASC), and inflammasome-secreted inflammatory factors (IL-1 beta). The expression of apoptosis (BCL-2, BAX, Caspase-3, Caspase-9) and necroptosis (RIPK1, RIPK33, MLKL, Caspase-8) increased. In addition, HEK293T human embryonic kidney cells were treated with trimethyltin chloride, and the results were similar to the tissue. In conclusion, TMT can induce oxidative stress, activate NF-kappa B pathway, and induce apoptosis and necroptosis through inflammasomes.

Automated summary

This study demonstrates the toxic effects of trimethyltin chloride on mouse kidneys and its mechanism, including the activation of NF-kappa B pathway and induction of apoptosis and necroptosis through inflammasomes.