Hydrogen Sulfide Gas Exposure Induces Necroptosis and Promotes Inflammation through the MAPK/NF-<i>κ</i>B Pathway in Broiler Spleen

Abstract

Hydrogen sulfide (H₂S) is one of the main pollutants in the atmosphere, which is a serious threat to human health. The decomposition of sulfur-containing organics in chicken houses could produce a large amount of H₂S, thereby damaging poultry health. In this study, one-day-old broilers were selected and exposed to 4 or 20 ppm of H₂S gas (0-3 weeks: 4 ± 0.5 ppm, 4-6 weeks: 20 ± 0.5 ppm). The spleen samples were collected immediately after the chickens were euthanized at 2, 4, and 6 weeks. The histopathological and ultrastructural observations showed obvious necrosis characteristics of H₂S-exposed spleens. H₂S exposure suppressed GSH, CAT, T-AOC, and SOD activities; increased NO, H₂O₂, and MDA content and iNOS activity; and induced oxidative stress. ATPase activities and the expressions of energy metabolism-related genes were significantly decreased. Also, the expressions of related necroptosis (RIPK1, RIPK3, MLKL, TAK1, TAB2, and TAB3) were significantly increased, and the MAPK pathway was activated. Besides, H₂S exposure activated the NF-<i>κ</i>B classical pathway and induced TNF-<i>α</i> and IL-1<i>β</i> release. Taken together, we conclude that H₂S exposure induces oxidative stress and energy metabolism dysfunction; evokes necroptosis; activates the MAPK pathway, eventually triggering the NF-<i>κ</i>B pathway; and promotes inflammatory response in chicken spleens.