2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)

It is important to note that 2-Amino-3-methylimidazole[4,5-f]quinoline (IQ) is one of the most common heterocyclic amines (HCAs), which is a class of mutagenic/carcinogenic harmful compounds mainly found in high-protein thermal processed foods and contaminated environments. However, the pre-carcinog...

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Autores principales:	Dan Li, Zhi Li, Tianchang Zhang, Bo Peng, Yan Zhang, Hongwen Sun, Shuo Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	HCAs IQ Hepatotoxicity ERS Autophagy Apoptosis Medicine R
Acceso en línea:	https://doaj.org/article/1dd0f651d29f4b7682d4d0468d8b0f3a
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spelling	oai:doaj.org-article:1dd0f651d29f4b7682d4d0468d8b0f3a2021-11-25T19:09:09Z2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)10.3390/toxins131108262072-6651https://doaj.org/article/1dd0f651d29f4b7682d4d0468d8b0f3a2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/826https://doaj.org/toc/2072-6651It is important to note that 2-Amino-3-methylimidazole[4,5-f]quinoline (IQ) is one of the most common heterocyclic amines (HCAs), which is a class of mutagenic/carcinogenic harmful compounds mainly found in high-protein thermal processed foods and contaminated environments. However, the pre-carcinogenic toxicity of IQ to the liver and its mechanism are poorly understood, further research is needed. In light of this, we exposed zebrafish to IQ (0, 8, 80, and 800 ng/mL) for 35 days, followed by comprehensive experimental studies. Histopathological and ultrastructural analysis showed that hepatocytes were damaged. TUNEL results showed that IQ induced apoptosis of liver cells, the expression of apoptosis factor gene was significantly increased, and the expression of Bcl-2 protein was significantly decreased. In addition, upregulated expression of the 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) and endoplasmic reticulum stress (ERS)-related factors transcription levels were elevated obviously, suggesting that IQ induced ERS. Decreased protein expression of autophagy-related 5 (Atg5)-Atg12, Beclin1, and LC3-II, increased protein expression of p62, and autophagy-related factors transcription levels were significantly decreased, suggesting that IQ inhibited autophagy. Overall, our research showed that the potential harm of IQ to the liver before the occurrence of liver cancer was related to ERS and its mediated autophagy and apoptosis pathways.Dan LiZhi LiTianchang ZhangBo PengYan ZhangHongwen SunShuo WangMDPI AGarticleHCAsIQHepatotoxicityERSAutophagyApoptosisMedicineRENToxins, Vol 13, Iss 826, p 826 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HCAs IQ Hepatotoxicity ERS Autophagy Apoptosis Medicine R
spellingShingle	HCAs IQ Hepatotoxicity ERS Autophagy Apoptosis Medicine R Dan Li Zhi Li Tianchang Zhang Bo Peng Yan Zhang Hongwen Sun Shuo Wang 2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)
description	It is important to note that 2-Amino-3-methylimidazole[4,5-f]quinoline (IQ) is one of the most common heterocyclic amines (HCAs), which is a class of mutagenic/carcinogenic harmful compounds mainly found in high-protein thermal processed foods and contaminated environments. However, the pre-carcinogenic toxicity of IQ to the liver and its mechanism are poorly understood, further research is needed. In light of this, we exposed zebrafish to IQ (0, 8, 80, and 800 ng/mL) for 35 days, followed by comprehensive experimental studies. Histopathological and ultrastructural analysis showed that hepatocytes were damaged. TUNEL results showed that IQ induced apoptosis of liver cells, the expression of apoptosis factor gene was significantly increased, and the expression of Bcl-2 protein was significantly decreased. In addition, upregulated expression of the 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) and endoplasmic reticulum stress (ERS)-related factors transcription levels were elevated obviously, suggesting that IQ induced ERS. Decreased protein expression of autophagy-related 5 (Atg5)-Atg12, Beclin1, and LC3-II, increased protein expression of p62, and autophagy-related factors transcription levels were significantly decreased, suggesting that IQ inhibited autophagy. Overall, our research showed that the potential harm of IQ to the liver before the occurrence of liver cancer was related to ERS and its mediated autophagy and apoptosis pathways.
format	article
author	Dan Li Zhi Li Tianchang Zhang Bo Peng Yan Zhang Hongwen Sun Shuo Wang
author_facet	Dan Li Zhi Li Tianchang Zhang Bo Peng Yan Zhang Hongwen Sun Shuo Wang
author_sort	Dan Li
title	2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)
title_short	2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)
title_full	2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)
title_fullStr	2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)
title_full_unstemmed	2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)
title_sort	2-amino-3-methylimidazo[4,5-f]quinoline triggering liver damage by inhibiting autophagy and inducing endoplasmic reticulum stress in zebrafish (<i>danio rerio</i>)
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1dd0f651d29f4b7682d4d0468d8b0f3a
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2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (<i>Danio rerio</i>)

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