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Alleviative Effect of Lactoferrin Interventions Against the Hepatotoxicity Induced by Titanium Dioxide Nanoparticles

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Abstract

The current study was designed to investigate the alleviative effect of lactoferrin interventions against the hepatotoxicity induced by titanium dioxide nanoparticles (TiO2-NPs). Thirty male Wistar rats were divided into six groups with 5 rats in each group. The first and second groups were intragastrically administered normal saline and TiO2-NPs (100 mg/kg body weight) as the negative control (NC) and TiO2-NP groups. The third, fourth, and fifth groups were intragastrically administered lactoferrin at concentrations of 100, 200, and 400 mg/kg body weight in addition to TiO2-NPs (100 mg/kg body weight). The sixth group was intragastrically administered Fuzheng Huayu (FZHY) capsules at a concentration of 4.6 g/kg body weight in addition to TiO2-NPs (100 mg/kg body weight) as the positive control group. After treatment for 4 weeks, the concentrations of lactoferrin were optimized based on the liver index and function results. Subsequently, the alleviative effects of lactoferrin interventions against TiO2-NP-induced hepatotoxicity in rat liver tissues, including the effects on histological damage, oxidative stress-related damage, inflammation, fibrosis, DNA damage, apoptosis, and gene expression, were investigated using histopathological, biochemical, and transcriptomic assays. The results showed that 200 mg/kg lactoferrin interventions for 4 weeks not only ameliorated the liver dysfunction and histopathological damage caused by TiO2-NP exposure but also inhibited the oxidative stress-related damage, inflammation, fibrosis, DNA damage, and apoptosis in the liver tissues of TiO2-NP-exposed rats. The transcriptomic results confirmed that the alleviative effect of lactoferrin interventions against the TiO2-NP exposure–induced hepatotoxicity was related to the activation of the PI3K/AKT signaling pathway.

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Acknowledgements

We would like to express our gratitude to Mr. Shu-sheng Mao from the Clinical Medicine Research Center in the Affiliated Hospital of Inner Mongolia Medical University for his kind help.

Funding

This work was supported by the National Natural Science Foundation of China (82060567 to Gang Liu), Natural Science Foundation of Inner Mongolia (2020BS08014 to Gang Liu and 2020LH08028 to Liya Su), ZhiYuan project of Inner Mongolia Medical University (ZY0120025 to Liya Su), Outstanding Young Talents Cultivation Program of Grassland Elite in Inner Mongolia (Q202286 to Gang Liu), and Young Talent Cultivation Program of Inner Mongolia Medical University (YKD2020QNCX016 to Jiaxin Sun).

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Authors and Affiliations

  1. Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China

    Wenqi Zhang, Jiaxin Sun, Fangyuan Liu, Shubin Li, Xianjue Wang, Liya Su & Gang Liu

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  1. Wenqi Zhang
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  2. Jiaxin Sun
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  3. Fangyuan Liu
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  4. Shubin Li
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  6. Liya Su
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  7. Gang Liu
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Contributions

All the authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Wenqi Zhang, Jiaxin Sun, Fangyuan Liu, Shubin Li, Xianjue Wang, Liya Su, and Gang Liu. The first draft of the manuscript was written by Gang Liu, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Gang Liu.

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Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Inner Mongolia Medical University (NMGYKD-20190043-R1).

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Supplementation Fig. 1Effect of lactoferrin supplementation on the gene expression pattern of TiO2-NPs exposed liver tissues. Note: NC, TiO2-NPs, Lactoferrin, and FZHY represent negative control, TiO2-NPs exposure, TiO2-NPs supplemented with lactoferrin, and TiO2-NPs supplemented with FZHY groups. Different lowercase letters in each column indicate significant differences between the corresponding experimental groups (p < 0.05).

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Zhang, W., Sun, J., Liu, F. et al. Alleviative Effect of Lactoferrin Interventions Against the Hepatotoxicity Induced by Titanium Dioxide Nanoparticles. Biol Trace Elem Res 202, 624–642 (2024). https://doi.org/10.1007/s12011-023-03702-3

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