Abstract
As a toxic trace element commonly found in food, cadmium (Cd) can cause severe liver injury. Our previous study showed that threonine (Thr) could significantly alleviate Cd toxicity in yeast. To investigate the effect of Thr on Cd-induced liver injury in mice, twenty-four mice were randomly divided into four groups: control, Cd, and low/high dose of Thr-treatment groups (0.04 and 0.08 mmol/kg/day, respectively). After 7 days of continuous treatment, the alleviative effect of Thr on liver injury in Cd-exposed mice was assessed. The results showed that Thr significantly reduced the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in Cd-exposed mice. Histological analysis showed that Thr decreased Cd-induced hepatic steatosis, zonal necrosis, and inflammatory cell infiltration. Thr also reduced the Cd-induced malondialdehyde (MDA) and O2− levels and restored superoxide dismutase (SOD) and catalase (CAT) activities in the liver. Further investigation showed that Thr significantly suppressed Cd-induced inflammatory response (tumor necrosis factor-α and interleukin-6) and restored the level of anti-apoptotic protein (Blc-2) but inhibited the elevation of pro-apoptotic proteins (Bax and caspase-3), as well as the activation of the PI3K/AKT signaling pathway in Cd-exposed mice. In conclusion, Thr alleviated Cd-induced liver injury through reducing Cd-induced oxidative stress, inflammation, and attenuating hepatocyte apoptosis via PI3K/AKT-related signaling pathway.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by the National Natural Science Foundation of China (No. 32172215 and 31701706), Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515010809 and 2021A1515012443).
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Zhijia Fang: designed, conceptualization, methodology, and critical revision. Yongbin Li: reviewing, editing, and interpretation. Xinran Wang: software and investigation. Linru Huang assisted in animal treatment and collection of biological samples. Lijun Sun: supervision. Qi Deng: software and validation. Jingwen Wang designed the in vivo study, data curation, and writing—original draft preparation.
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Fang, Z., Li, Y., Wang, J. et al. Alleviative Effect of Threonine on Cadmium-Induced Liver Injury in Mice. Biol Trace Elem Res 201, 4437–4446 (2023). https://doi.org/10.1007/s12011-022-03506-x
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DOI: https://doi.org/10.1007/s12011-022-03506-x