• SeD and TMT induce structural damage and immune dysfunction in the poultry thymus. • The miR-7480-5p /SIRT3/GSH axis plays a key role in SeD and TMT-induced thymic ferroptosis. • SeD and TMT disrupt the MQC, causing excessive mitophagy and mitochondrial dysfunction. • Impaired glutathione metabolism is at the heart of the joint toxicity of SeD and TMT. • Co-exposure to SeD and TMT exacerbates thymic mitochondrial oxidative stress and ferroptosis. Trimethyltin chloride (TMT) is a widespread environmental contaminant with significant biotoxicity. Selenium is an essential trace element, and its deficiency can exacerbate pollutant toxicity, with ferroptosis and mitochondrial stress as key events. This research aimed to explore the influence of combined selenium deficiency (SeD) and TMT exposure on poultry thymus toxicity and the underlying molecular mechanisms. Broiler chicken and MDCC-MSB-1 cell models were established with individual or combined SeD and TMT treatment. Mechanisms of thymic injury were explored using transcriptomics, immunofluorescence, Western blot, and other methods. The study demonstrated that both individual and combined SeD and TMT exposure induced thymic structural abnormalities, mitochondrial oxidative stress, disruption of mitochondrial homeostasis and function, mitophagy, and ferroptosis. Further investigations revealed that mitochondrial oxidative stress and mitophagy regulate ferroptosis, with combined exposure causing more severe damage. Mechanistically, TMT and SeD regulated mitochondrial quality control (MQC) system and ferroptosis through the miR-7480-5p /SIRT3/GSH axis. This study reveals that SeD and TMT induce thymic injury by triggering mitochondrial dysfunction and ferroptosis via the miR-7480-5p /SIRT3/GSH axis, providing novel mechanistic insights and potential intervention targets and potential interventions for TMT pollution in selenium-deficient regions.
Gao et al. (Sun,) studied this question.