Ammonia-induced oxidative stress triggered proinflammatory response and apoptosis in pig lungs
Xiaoping Li , Daojie Li , Long Shen , Di Zhang , Xiaotong Wang , Qiankun Wang , Wenhao Qin , Yun Gao
DOI:10.1016/j.jes.2022.05.005
Received November 28, 2021,Revised , Accepted May 07, 2022, Available online May 19, 2022
Volume 35,2023,Pages 683-696
Ammonia, a common toxic gas, is not only one of the main causes of haze, but also can enter respiratory tract and directly affect the health of humans and animals. Pig was used as an animal model for exploring the molecular mechanism and dose effect of ammonia toxicity to lung. In this study, the apoptosis of type II alveolar epithelial cells was observed in high ammonia exposure group using transmission electron microscopy. Gene and protein expression analysis using transcriptome sequencing and western blot showed that low ammonia exposure induced T-cell-involved proinflammatory response, but high ammonia exposure repressed the expression of DNA repair-related genes and affected ion transport. Moreover, high ammonia exposure significantly increased 8-hydroxy-2-deoxyguanosine (8-OHdG) level, meaning DNA oxidative damage occurred. In addition, both low and high ammonia exposure caused oxidative stress in pig lungs. Integrated analysis of transcriptome and metabolome revealed that the up-regulation of LDHB and ND2 took part in high ammonia exposure-affected pyruvate metabolism and oxidative phosphorylation progress, respectively. Inclusion, oxidative stress mediated ammonia-induced proinflammatory response and apoptosis of porcine lungs. These findings may provide new insights for understanding the ammonia toxicity to workers in livestock farms and chemical fertilizer plants.
