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Chronic exposure to low doses of Pb induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels of mice

Author:
Luo, Ting, Shen, Manlu, Zhou, Jiajie, Wang, Xiaoyu, Xia, Jizhou, Fu, Zhengwei, Jin, Yuanxiang
Source:
Environmental toxicology 2019 v.34 no.4 pp. 521-529
ISSN:
1520-4081
Subject:
adults, alanine transaminase, alkaline phosphatase, aspartate transaminase, body weight, catalase, chronic exposure, fatty acid metabolism, glutathione, heavy metals, hepatotoxicity, histopathology, lead, liver, males, malondialdehyde, metallothionein, mice, oral exposure, peroxisome proliferator-activated receptors, pharmacokinetics, protein content, reactive oxygen species, signal transduction, superoxide dismutase, transcriptome, transcriptomics
Abstract:
Lead (Pb), a non‐essential heavy metal, is a major global environmental contaminant with serious toxicological consequences. In the present study, the effects on hepatotoxicity of mice with chronic exposure to low doses of Pb were evaluated. While oral exposure to 0.03 or 0.1 mg/L Pb for 15 weeks in male adult mice had no significant effect on body weights, Pb exposure resulted in liver histopathological effects and increase of hepatic activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). In addition, hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) significantly accumulated after treatment. Conversely, glutathione (GSH) decreased significantly in both 0.03 and 0.1 mg/L Pb‐treated groups. Moreover, the hepatic activities of superoxide dismutase 1 (SOD) and catalase (CAT) increased significantly following treatment with 0.1 mg/L Pb for 15 weeks, concomitant with increases in transcriptions of hepatic Sod, Cat, and Gpx. Furthermore, transcriptions of hepatic metallothionein (MT), zinc transporter 5 (Znt5) and copper transporter 1 (Ctr1), and subsequent protein levels were also increased in liver of mice when exposed to 0.1 mg/L Pb for 15 weeks. In addition, the transcriptome data showed that Pb has substantial influence on several pathways, including PPAR signaling pathways, AMPK signaling pathways, fatty acid metabolism, and drug metabolism. Our data suggested that chronic Pb exposure could induce hepatotoxicity at the physiological, biochemical, and transcriptomic levels in mice.
Agid:
6324423