Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

Kwon, Hyuk-Cheol; Kim, Dohyun; Jeong, Chang-Hee; Kim, Yea‐Ji; Han, Jiyeon; Lim, Seung Woon; Shin, Dong-Min; Kim, Dong-Wook; Han, Sung Gu

doi:10.3390/foods10102242

Cited by 9 publications

(2 citation statements)

References 47 publications

(64 reference statements)

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“…Several studies have demonstrated that cell death is induced via various pathways following TEB exposure. In some studies, TEB induced ROS-mediated cell death via mitochondrial dysfunction in human colon carcinoma, cardiac, and hepatic cells [13,34,35]. In other studies, TEB induced apoptosis via ROS in the kidney and liver [36,37], similar to previous studies.…”

Section: Discussionsupporting

confidence: 81%

Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines

Lee¹,

Lee

Park

2023

Toxics

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Tebuconazole (TEB) is a triazole fungicide used to increase crop production by controlling fungi, insects, and weeds. Despite their extensive use, people are concerned about the health risks associated with pesticides and fungicides. Numerous studies have defined the cellular toxicity of triazole groups in pesticides, but the mechanisms of TEB toxicity in bovine mammary gland epithelial cells (MAC-T cells) have not yet been studied. Damage to the mammary glands of dairy cows directly affects milk production. This study investigated the toxicological effects of TEB on MAC-T cells. We found that TEB decreases both cell viability and proliferation and activates apoptotic cell death via the upregulation of pro-apoptotic proteins, such as cleaved caspases 3 and 8 and BAX. TEB also induced endoplasmic reticulum (ER) stress via the upregulation of Bip/GRP78; PDI; ATF4; CHOP; and ERO1-Lα. We found that TEB induced mitochondria-mediated apoptotic MAC-T cell death by activating ER stress. This cell damage eventually led to a dramatic reduction in the expression levels of the milk-protein-synthesis-related genes LGB; LALA; CSN1S1; CSN1S2; and CSNK in MAC-T cells. Our data suggest that the exposure of dairy cows to TEB may negatively affect milk production by damaging the mammary glands.

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Section: Discussionsupporting

confidence: 81%

Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines

Lee¹,

Lee

Park

2023

Toxics

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“…Hepatotoxicity is also observed with signs of hepatocyte dystrophy [4]. In addition, studies of tebuconazole accumulation in HepG2 cells and associated lipid metabolic disorders led to suggestion that human exposure to tebuconazole may be a risk factor for the development of nonalcoholic fatty liver disease [5].…”

mentioning

confidence: 99%

Fatty acid profile of the liver lipids under acute fungicide action and intake of a biologically active preparation in rats

Khyzhnyak¹,

Мидык²,

Velinska³

et al. 2022

Ukr.Biochem.J.

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The widespread use of fungicides in agriculture leads to a negative consequences for both humans and the environment. The acute effect of fungicides containing tebuconazole alone or in combination with triadimefon on fatty acid (FAs) composition of the total lipids in the liver of rats was studied. FAs content was analyzed by gas chromatography with the use of flame ionization detector. The results obtained indicate that the acute effect of triazole fungicides one-time oral administration to rats is characterized by toxic reactions and is accompanied by the total liver lipids FAs profile redistribution, similar for the studied fungicides. In particular, the reduction in the total content of monounsaturated FAs (by 26% – 37%) and in the ω3/ω6 ratio was observed. It was demonstrated that the subsequent two-week introduction of the preparation based on Milk thistle seeds oil extract had a positive effect and improved the FAs profile of lipids in dynamics after fungicide intake. Keywords: fatty acids, fungicides, Milk thistle seeds extract, rat liver lipids, triazoles

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Cellular and molecular effects of fipronil in lipid metabolism of HepG2 and its possible connection to non‐alcoholic fatty liver disease

Pansa,

Molica,

de Oliveira Júnior

et al. 2023

J Biochem & Molecular Tox

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Nonalcoholic fatty liver disease (NAFLD) is a global public health problem that affects more than a quarter of the population. The development of this disease is correlated with metabolic dysfunctions that lead to lipid accumulation in the liver. Pesticides are one of etiologies that support NAFLD establishment. Therefore, the effects of the insecticide fipronil on the lipid metabolism of the human hepatic cell line, HepG2, was investigated, considering its widespread use in field crops and even to control domestic pests. To address the goals of the study, biochemical, cellular, and molecular analyses of different concentrations of fipronil in cell cultures were investigated, after 24 h of incubation. Relevant metabolites such as triglycerides, glucose levels, β‐oxidation processes, and gene expression of relevant elements correlated with lipid and metabolism of xenobiotics were investigated. The results suggested that at 20 μM, the pesticide increased the accumulation of triglycerides and neutral lipids by reducing fatty acid oxidation and increasing de novo lipogenesis. In addition, changes were observed in genes that control oxidative stress and the xenobiotic metabolism. Together, the results suggest that the metabolic changes caused by the insecticide fipronil may be deleterious if persistent, favoring the establishment of hepatic steatosis.

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Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

Cited by 9 publications

References 47 publications

Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines

Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines

Fatty acid profile of the liver lipids under acute fungicide action and intake of a biologically active preparation in rats

Cellular and molecular effects of fipronil in lipid metabolism of HepG2 and its possible connection to non‐alcoholic fatty liver disease

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