Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice
Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics t...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322008430 |
| _version_ | 1798004580829626368 |
|---|---|
| author | Yan Zhang Jialu Bao Xincheng Gong Wanyu Shi Tao Liu Xiaodan Wang |
| author_facet | Yan Zhang Jialu Bao Xincheng Gong Wanyu Shi Tao Liu Xiaodan Wang |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics to explore the potential mechanism of MCZ on liver injury. MCZ group was given 100 mg/kg MCZ every day, and the C group was given 0.2 mL of deionized water every day. One hundred mg/kg MCZ led to unclear hepatocyte structure and hemorrhagic inflammatory cell infiltration. Transcriptomics and metabolomics analyses showed that the MCZ group resulted in 326 differentially expressed genes (DEGs) and 179 differential metabolites. Joint analysis showed that DEGs and differential metabolites were mainly enriched in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. We found that MCZ could increase the content of reactive oxygen species (ROS) and reduce the activities of superoxide dismutase (SOD) and catalase (CAT). The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p < 0.05). Our results suggest that AMPK and mitogen‑activated protein kinase (MAPK) signaling pathways play an important role in MCZ-induced liver injury and are the key mechanisms for understanding the hepatotoxicity of MCZ. |
| first_indexed | 2024-04-11T12:25:49Z |
| format | Article |
| id | doaj.art-76ab377f030845b3ac1328c361228381 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T12:25:49Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-76ab377f030845b3ac1328c3612283812022-12-22T04:23:56ZengElsevierEcotoxicology and Environmental Safety0147-65132022-09-01243114003Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of miceYan Zhang0Jialu Bao1Xincheng Gong2Wanyu Shi3Tao Liu4Xiaodan Wang5College of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, ChinaCollege of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, ChinaCollege of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China; Veterinary Biological Technology Innovation Center of Hebei Province, Baoding 071001, ChinaCollege of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China; Veterinary Biological Technology Innovation Center of Hebei Province, Baoding 071001, ChinaCollege of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China; Veterinary Biological Technology Innovation Center of Hebei Province, Baoding 071001, ChinaCollege of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China; Veterinary Biological Technology Innovation Center of Hebei Province, Baoding 071001, China; Corresponding author at: College of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China.Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics to explore the potential mechanism of MCZ on liver injury. MCZ group was given 100 mg/kg MCZ every day, and the C group was given 0.2 mL of deionized water every day. One hundred mg/kg MCZ led to unclear hepatocyte structure and hemorrhagic inflammatory cell infiltration. Transcriptomics and metabolomics analyses showed that the MCZ group resulted in 326 differentially expressed genes (DEGs) and 179 differential metabolites. Joint analysis showed that DEGs and differential metabolites were mainly enriched in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. We found that MCZ could increase the content of reactive oxygen species (ROS) and reduce the activities of superoxide dismutase (SOD) and catalase (CAT). The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p < 0.05). Our results suggest that AMPK and mitogen‑activated protein kinase (MAPK) signaling pathways play an important role in MCZ-induced liver injury and are the key mechanisms for understanding the hepatotoxicity of MCZ.http://www.sciencedirect.com/science/article/pii/S0147651322008430MancozebTranscriptomicsMetabonomicsLiver |
| spellingShingle | Yan Zhang Jialu Bao Xincheng Gong Wanyu Shi Tao Liu Xiaodan Wang Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice Ecotoxicology and Environmental Safety Mancozeb Transcriptomics Metabonomics Liver |
| title | Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice |
| title_full | Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice |
| title_fullStr | Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice |
| title_full_unstemmed | Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice |
| title_short | Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice |
| title_sort | transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice |
| topic | Mancozeb Transcriptomics Metabonomics Liver |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322008430 |
| work_keys_str_mv | AT yanzhang transcriptomicsandmetabolomicsrevealedthemolecularmechanismofthetoxiceffectofmancozebonliverofmice AT jialubao transcriptomicsandmetabolomicsrevealedthemolecularmechanismofthetoxiceffectofmancozebonliverofmice AT xinchenggong transcriptomicsandmetabolomicsrevealedthemolecularmechanismofthetoxiceffectofmancozebonliverofmice AT wanyushi transcriptomicsandmetabolomicsrevealedthemolecularmechanismofthetoxiceffectofmancozebonliverofmice AT taoliu transcriptomicsandmetabolomicsrevealedthemolecularmechanismofthetoxiceffectofmancozebonliverofmice AT xiaodanwang transcriptomicsandmetabolomicsrevealedthemolecularmechanismofthetoxiceffectofmancozebonliverofmice |