Screening and validation of biomarkers for cadmium-induced liver injury based on targeted bile acid metabolomics

Abstract

Although cadmium (Cd) is a toxic heavy metal that reportedly causes liver injury, few studies have investigated biomarkers of Cd-induced liver injury. The purpose of this study is to investigate the role of bile acid (BA) in Cd-induced liver injury and determine reliable and sensitive biochemical parameters for the diagnosis of Cd-induced liver injury. In this study, 48 Sprague-Dawley rats were randomly divided into six groups and administered either normal saline or 2.5, 5, 10, 20, and 40 mg/kg/d cadmium chloride for 12 weeks. A total of 403 subjects living in either a control area (n = 135) or Cd polluted area (n = 268) of Dongdagou-Xinglong (DDGXL) cohort were included, a population with long-term low Cd exposure. The BA profiles in rats' liver, serum, caecal contents, faeces, and subjects' serum were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Changes in rats' and subjects' liver injury indices, rats' liver pathological degeneration, and rats' liver and subjects' blood Cd levels were also measured. Cadmium exposure caused cholestasis and an increase in toxic BAs, leading to liver injury in rats. Among them, glycoursodeoxycholic acid (GUDCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and taurodeoxycholate acid (TDCA) are expected to be potential biomarkers for the early detect of Cd-induced liver injury. Serum BAs can be used to assess Cd-induced liver injury as a simple, feasible, and suitable method in rats. Serum GUDCA, GLCA, TDCA, and TLCA were verified to be of value to evaluate Cd-induced liver injury and Cd exposure in humans. These findings provided evidence for screening and validation of additional biomarkers for Cd-induced liver injury based on targeted BA metabolomics.

Keywords: Bile acid (BA); Biomarkers; Cadmium exposure; Liver injury.