Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen

Background: Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, and exposure to it has been shown to be associated with a variety of toxic effects. As can be accumulated in the spleen, the largest peripheral lymphatic organ, and long-term exposure to As can lead to splenic injury.Methods: In this study, a Sprague-Dawley (SD) rat model of As poisoning was established by feeding method, aiming to explore the molecular mechanism of As-induced immune injury through the combined analysis of proteomics and metabolomics of rats’ spleen.Results: The results showed that a total of 134 differentially expressed proteins (DEPs) (6 up-regulated and 128 down-regulated) and 182 differentially expressed metabolites (DEMs) (127 up-regulated and 55 down-regulated) were identified in the spleen in the As poisoning group versus the control group (As/Ctrl). The proteomic results highlight the role of hypoxia-inducible factors (HIF), natural killer cells, and ribosomes. The main pathways of metabolic disruption included arachidonic acid (AA) metabolism, glycerophospholipid metabolism and folate single-carbon pool. These two omics analyses suggest that Hmox1, Stat3, arachidonic acid, phosphatidylcholine and leukotriene B4 may play key roles in the mechanism of immune injury to the spleen by As exposure.Conclusion: As exposure can cause spleen damage in rats. As induced alterations in characteristic proteins and metabolites of the rat spleen. This may provide a basis for further understanding of the molecular mechanisms of multi-organ splenic immune injury by As exposure.