Abstract
Ammonia is a significant pollutant in the livestock houses and the atmospheric environment, and excessive ammonia would harm the health of livestock and breeders. Previous studies have shown that ammonia exposure could damage the tissue structure of the nervous system, but the molecular mechanism of ammonia-induced hypothalamus damage was still unclear. The purpose of this study was to determine the role of excessive ammonia in abnormal autophagy of pig hypothalamus and whether selenomethionine would have a mitigating effect on ammonia toxicity. Twenty-four 18-week pigs were randomly divided into four groups: the control group (C group), the selenium group (Se group), the ammonia + selenium group (A + Se group), and the ammonia group (A group). In our study, the expression levels of NF-κB, IL-1β, iNOS, TNF-α, IKK-α, p-IKK-α, Nrf2, ATG5, ATG 10, ATG 12, LC3 I/II, HSP60, HSP70, and HSP90 were increased after ammonia exposure; meanwhile, IFN-γ, IKB-α, p-IKB-α, Keap1, P62, mTOR, AKT, p-AKT, PI3K, SQSTM, and Beclin1 showed decreasing trends. The results indicated that excessive ammonia inhalation inhibited the AKT/mTOR pathway to acclerated autophagy through oxidative stress-mediated inflammation in the porcine hypothalamus. L-selenomethionine could alleviate hypothalamus injury induced by ammonia exposure.
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Data Availability
Original data used and generated in this study are available from the corresponding authors on request with a completed Data Transfer Agreement. The raw sequencing files can be obtained through the National Center for Biotechnology Information website (Accession No. PRJNA741846).
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Acknowledgements
The study was supported by the Earmarked Fund for the China Agriculture Research System of MOF and MARA (Project No. CARS-35-05B). The authors would thank Lian Chuan-Biotechnology Co., Ltd (Hangzhou, China) for their assistance during transcriptome sequencing. The experiment also got support from the animal welfare and healthy breeding team of Northeast Agriculture University.
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Jianxing Wang: writing—original draft, methodology, investigation, formal analysis, data curation. Jing Wang and Yutao Li: writing—review and editing, investigation, formal analysis, animal breeding, conceptualization. Qi Han and Yulai Wang: methodology, investigation, language revision. Honggui Liu and Jun Bao: supervision, writing—review and editing, project administration, funding acquisition. All authors read and approved the final manuscript.
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Wang, J., Wang, J., Li, Y. et al. Organic Selenium Alleviates Ammonia-Mediated Abnormal Autophagy by Regulating Inflammatory Pathways and the Keap1/Nrf2 Axis in the Hypothalamus of Finishing Pigs. Biol Trace Elem Res 201, 3812–3824 (2023). https://doi.org/10.1007/s12011-022-03452-8
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DOI: https://doi.org/10.1007/s12011-022-03452-8