Selenium Alleviates Ammonia-Induced Splenic Cell Apoptosis and Inflammation by Regulating the Interleukin Family/Death Receptor Axis and Nrf2 Signaling Pathway

Abstract

Ammonia (NH₃) is a harmful gas in livestock houses. So far, many researchers have demonstrated that NH₃ is detrimental to animal and human organs. Selenium (Se) is one of the essential trace elements in the body and has a good antioxidant effect. However, there was little conclusive evidence that Se alleviated NH₃ poisoning. To investigate the toxic mechanism of NH₃ on pig spleen and the antagonistic effect of L-selenomethionine, a porcine NH₃-poisoning model and an L-selenomethionine intervention model were established in this study. Our results showed that NH₃ exposure increased the apoptosis rate, while L-selenomethionine supplementation alleviated the process of excessive apoptosis. Immunofluorescence staining, real-time quantitative polymerase chain reaction (qRT-PCR), and western blot results confirmed that exposure to NH₃ changed the expression levels of interleukin family factors, apoptosis, death receptor, and oxidative stress factors. Our study further confirmed that excessive NH₃ induced inflammatory response and mediated necroptosis leading to cell apoptosis by activating the Nrf2 signaling pathway. Excessive NH₃ could mediate spleen injury through oxidative stress-induced mitochondrial dynamics disorder. L-Selenomethionine could alleviate inflammation and abnormal apoptosis by inhibiting the IL-17/TNF-α/FADD axis. Our study would pave the way for comparative medicine and environmental toxicology.