Immunosuppression, oxidative stress, and apoptosis in pig kidney caused by ammonia: Application of transcriptome analysis in risk assessment of ammonia exposure

Ammonia (NH₃) is a recognized environmental contaminant around the world and has adverse effects on animal and human health. However, the mechanism of the renal toxicity of NH₃ is not well understood. Pigs are considered an ideal model for biomedical and toxicological research because of the similarity to humans in physiological and biochemical basis. Therefore, in this study, twelve pigs were selected as research objects and randomly divided into two groups, namely the control group and the NH₃ group. The formal experiment lasted 30 days. The effects of excessive NH₃ inhalation on the kidney of fattening pig were evaluated by chemical analysis, ELISA, transcriptome analysis and real-time quantitative PCR (qRT-PCR) from the renal antioxidant level, renal function, blood ammonia content and gene level. Our results showed that excessive NH₃ exposure could cause an increase in blood NH₃ content, a reduction in renal GSH-Px, SOD and GSH, as well as an increase in MDA levels and an increase in serum creatinine, urea and uric acid levels. In addition, transcriptome analysis showed that NH₃ exposure caused changes in 335 differentially expressed genes (DEGs) (including 126 up-regulated DEGs and 109 down-regulated DEGs). Some highly expressed DEGs were enriched into GO terms associated with immune function, oxidative stress, and apoptosis and were verified by qRT-PCR. The qRT-PCR results were comsistent with the transcriptome results. Our results indicated that NH₃ exposure could cause changes in renal transcriptional profiles and kidney function, and induce kidney damage in the fattening pigs through oxidative stress, immune dysfunction and apoptosis. Our present study provides novel insights into the immunotoxicity mechanism of NH₃ on kidney.