Hexavalent chromium induces ferroptosis in small intestinal tissue of broilers through GPX4/HMGB1/p38-MAPK pathway

六价铬通过GPX4/HMGB1/p38-MAPK通路诱导肉鸡小肠组织发生铁死亡。

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Abstract

As a major environmental heavy metal pollutant, hexavalent chromium (Cr(VI)) causes irreversible damage to animals and humans. Nevertheless, how Cr(VI) exposure causes intestinal damage in broilers remains inadequately explored. This study explores Cr(VI)-induced poisoning using potassium dichromate to build a Cr(VI) poisoning model. The results indicate that Cr(VI) exposure evidently reduced the body weight and the functions of liver and kidney in broilers. Histopathological analysis revealed different degrees of structural damage in all three segments of the small intestines by Cr(VI) exposure. Moreover, Cr(VI) exposure downregulated ZO-1, Occludin, and Claudin-1, while altering the diversity of cecal microbiota to impair the intestinal barrier function. Additionally, with increasing Cr(VI) concentration, the contents of Fe(2+), ROS, and LPO in all three intestinal segments showed a dose-dependent increase. The levels of GPX4, SLC7A11, FTL, and FTH1 were downregulated by Cr(VI), while the levels of p38-MAPK, phosphorylated p38, TFR1, and HMGB1 were upregulated. This study suggests that Cr(VI)-induced ROS can trigger ferroptosis through the GPX4/HMGB1/p38-MAPK pathway, leading to intestinal barrier dysfunction and ultimately reducing the production performance of broilers. This provides foundation of theory for understanding the effects of Cr(VI) exposure on the small intestine.

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