Green tea polyphenols alleviate di-(2-ethylhexyl) phthalate-induced liver injury in mice

Heng Shi; Xin-Hai Zhao; Qin Peng; Xian-Ling Zhou; Si-Si Liu; Chuan-Chuan Sun; Qiu-Yu Cao; Shi-Ping Zhu; Sheng-Yun Sun

doi:10.3748/wjg.v29.i34.5054

Green tea polyphenols alleviate di-(2-ethylhexyl) phthalate-induced liver injury in mice

World J Gastroenterol. 2023 Sep 14;29(34):5054-5074. doi: 10.3748/wjg.v29.i34.5054.

Authors

Heng Shi^{1

2}, Xin-Hai Zhao¹, Qin Peng², Xian-Ling Zhou¹, Si-Si Liu³, Chuan-Chuan Sun¹, Qiu-Yu Cao¹, Shi-Ping Zhu¹, Sheng-Yun Sun⁴

Affiliations

¹ Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 522000, Guangdong Province, China.
² Department of Gastroenterology, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China.
³ Department of Pathology, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China.
⁴ Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 522000, Guangdong Province, China. shengyunsun2020@163.com.

Abstract

Background: Di (2-ethylhexyl) phthalate (DEHP) is a common plasticizer known to cause liver injury. Green tea is reported to exert therapeutic effects on heavy metal exposure-induced organ damage. However, limited studies have examined the therapeutic effects of green tea polyphenols (GTPs) on DEHP-induced liver damage.

Aim: To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage.

Methods: C57BL/6J mice were divided into the following five groups: Control, model [DEHP (1500 mg/kg bodyweight)], treatment [DEHP (1500 mg/kg bodyweight) + GTP (70 mg/kg bodyweight), oil, and GTP (70 mg/kg bodyweight)] groups. After 8 wk, the liver function, blood lipid profile, and liver histopathology were examined. Differentially expressed micro RNAs (miRNAs) and mRNAs in the liver tissues were examined using high-throughput sequencing. Additionally, functional enrichment analysis and immune infiltration prediction were performed. The miRNA-mRNA regulatory axis was elucidated using the starBase database. Protein expression was evaluated using immunohistochemistry.

Results: GTPs alleviated DHEP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, liver fibrosis, and mitochondrial and endoplasmic reticulum lesions in mice. The infiltration of macrophages, mast cells, and natural killer cells varied between the model and treatment groups. mmu-miR-141-3p (a differentially expressed miRNA), Zcchc24 (a differentially expressed mRNA), and Zcchc24 (a differentially expressed protein) constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice.

Conclusion: This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, and partial liver fibrosis, and regulate immune cell infiltration. Additionally, an important miRNA-mRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.

Keywords: Di(2-ethylhexyl) phthalate; Fatty liver disease; Green tea polyphenols; Immune; Liver fibrosis; Mitochondria.