Nickel Exposure Via Different Routes Induces Hepato-Intestinal Injury and Conjugated BileAcid Dysregulation in Mice

Nickel (Ni) ingestion is associated with hepatic and gastrointestinal toxicity, but its effects on bile acid metabolism and the role of exposure routes remain unclear.In this study, male mice were exposed to NiCl (1.6mg/mL) via gavage or intraperitoneal injection for 28 days.Histological, ultrastructural, and immunohistochemical analyses were conducted on liver and intestinal tissues.Liver transcriptome sequencing and fecal bile acid profiling (via LC-MS/MS) were performed.Nickel exposure caused significant intestinal and liver damage, with intraperitoneal injections producing more severe effects than gavage.TUNEL and PCNA staining revealed increased apoptosis and reduced cell proliferation in the liver.Transmission electron microscopy showed mitochondrial swelling and cristae loss.Bile acid profiling indicated reduced secretion of bile acids, particularly conjugated bile acids.Transcriptomic analysis identified altered expression in bile acid transport and cholesterol metabolism genes, including down regulation of Abcb11, Slc22a7, and Aqp8.The result of this experiment confirmed that nickel could induce hepato-intestinal toxicity and disrupt bile acid metabolism in a route-dependent manner.These findings provide new insights into heavy metal toxicity and bile acid regulation.