Integrated analysis of transcriptomics and metabonomics profiles in aflatoxin B1-induced hepatotoxicity in rat

Lu, Xiaoyan; Hu, Bin; Shao, Li; Tian, Yu; Jin, Tingting; Jin, Yachao; Shen, Ji; Fan, Xiaohui

doi:10.1016/j.fct.2013.01.020

Cited by 68 publications

(63 citation statements)

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“…These results may illustrate that lipid metabolism disorder may occur in the T1DM/AFB1 group. Disorder of lipid metabolism in rat liver after AFB1 exposure was also reported by Lu, et al [29]. …”

Section: Discussionsupporting

confidence: 75%

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The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice

et al. 2017

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In nanoflow liquid chromatography-matrix-assisted laser desorption/ionization tandem time-of-flight (nanoLC-MALDI-TOF/TOF) approaches, it is critical to directly apply small amounts of the sample elutes on the sample target using a nanoLC system due to its low flow rate of 200 ~ 300 nl/min. It is recommended to apply a sheath liquid containing a matrix with a several μL/min flow rate at the end of the nanoLC column to ensure a larger co-eluted droplet for more reproducible sample spotting and avoid the laborious task of post-manual matrix spotting. In this study, to achieve a better nanoLC-MALDI performance on sample spotting, we first compared α-Cyano-4-hydroxycinnamic acid (CHCA) solvent composition for efficiently concentrating nanoLC elutes on an anchor chip. The solvent composition of isopropanol (IPA): acetonitrile (ACN):acetone:0.1% Trifluoroacetic acid (TFA) (2:7:7:2) provided strong and homogeneous signals with higher peptide ion yields than the other solvent compositions. Then, nanoLC-MALDI-TOF/TOF was applied to study the impact of aflatoxin B1 on the liver proteome from diabetes mellitus type 1 mice. Aflatoxin B1 (AFB1), produced by Aspergillus flavus and Aspergillus parasiticus is a carcinogen and a known causative agent of liver cancer. To evaluate the effects of long-term exposure to AFB1 on type 1 diabetes mellitus (TIDM), the livers of T1DM control mice and mice treated with AFB1 were analyzed using isotope-coded protein labeling (ICPL)-based quantitative proteomics. Our results showed that gluconeogenesis, lipid, and oxidative phosphorylation mechanisms, normally elevated in T1DM, were disordered following AFB1 treatment. In addition, major urinary protein 1 (MUP1), an indicator of increased insulin sensitivity, was significantly decreased in the T1DM/AFB1 group and may have resulted in higher blood glucose levels compared to the T1DM group. These results indicate that T1DM patients should avoid the AFB1 intake, as they could lead to increased blood glucose levels and disorders of energy-producing mechanisms.

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Section: Discussionsupporting

confidence: 75%

“…Based on transcriptomics and metabonomics results, disorder of gluconeogenesis was also found in rat liver after AFB1 exposure. [29]…”

Section: Discussionmentioning

confidence: 99%

The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice

et al. 2017

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“…Through a cross-omics method, it is demonstrated that the major metabolic consequences of acute toxicity of aflatoxin B1, one of the well-known hepatotoxic mycotoxin, are associated with gluconeogenesis and lipid metabolism pathways 9 . Moreover, inorganic arsenic methylation in mouse liver may be saturated under chronic exposure to the element based on an integrated-omics approach 10 .…”

mentioning

confidence: 99%

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies

Yang

Chen

et al. 2014

Sci Rep

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The mycotoxin ochratoxin A (OTA) is found widely in agricultural commodities. OTA can induce various toxicities. In this study, rats were gavaged with OTA for different weeks. Then, the expression of microRNAs, mRNAs and proteins were measured in the rat livers treated with OTA for 13 weeks. Our sequencing data suggests that the medial and the high doses of OTA exert different effects on livers. Five distinctive pathways were induced after OTA treatment as collectively demonstrated at miRNA, mRNA and protein levels. Two (primary bile acid biosynthesis, and metabolism of xenobiotics by cytochrome P450) are directly associated with liver damage, whereas the remaining pathways (arginine and proline metabolism, cysteine and methionine metabolism, and PPAR signaling pathway) cause metabolic disease. This study reveals OTA-induced early hepatotoxicity for the first time by combining multi-omics methods. The novel metabolic pathways may contribute to the pathogenesis of metabolic diseases later in life.O chratoxin A (OTA) is a low molecular weight mycotoxin produced by certain strains of filamentous fungi of the Aspergillus and Penicillium genera and has been detected in a large variety of agricultural commodities. OTA carries potential health-associated risks and has been classified as a possible human carcinogen (group 2B) by the International Agency for Research on Cancer 1 . OTA has previously been found to induce various toxic effects including nephrotoxicity, hepatotoxicity, immunotoxicity, genotoxicity, carcinogenicity, teratogenicity, neurotoxicity and mutagenicity.The liver is one of the major target organs of OTA biotransformation. Although, some early hepatotoxicity studies employed relative high concentrations of OTA and found remarkable liver lesion 2,3 , lower doses of OTA did not provoke significant pathological changes 4-6 . Most of the previous studies have been extensively focused on OTA-induced kidney damage, less on liver. However, it is still unknown how OTA affects the liver which is the largest detoxification organ of body. Therefore, the identification of early hepatotoxicity can be helpful to understand the mechanism of some diseases that may be developed and progressed by OTA in later stage, and to prevent these diseases in early stage to improve human health.Omics approaches, such as transcriptome and proteome, are promising to detect the pathological changes of liver at a molecular level. Till date, omics technology has been employed only in a few studies to understand the mechanism of OTA hepatotoxicity. Moreover, a high-throughput microarray profiling study on HepG2 liver cell transcriptome demonstrated that multiple hepatic metabolism genes are modulated by OTA exposure 7 . In addition, proteomic approaches have helped identify key proteins in the livers of pigs treated with OTA 8 . These omics approaches have widened our view about OTA hepatotoxicity, however the mechanism of OTA actions remains largely unknown.Recently, microRNAs (miRNAs) in animals and plants are shown to play an impor...

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“…However, P53 activation is induced by a number of stress signals, including oxidative stress, DNA damage, and activated oncogenes. The oxidative damage due to AFB1 exposure might induce activation of P53 [25]. Tong et al [26] mentioned that P53 mutations may be a late event that promotes carcinoma development in the liver.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Role of Aflatoxin B1 on the Liver of Wheat Milling Workers

Saad-Hussein¹,

Abdalla²,

Shousha³

et al. 2014

Open Access Maced J Med Sci

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Aim: The study aimed to estimate oxidative role of aflatoxin B1 (AFB1) on the liver in wheat milling workers. Materials and Methods:Case-control study was conducted to compare between the levels of AFB1/albumin (AFB1/alb), liver enzymes (ALT, AST, GGT, and ALP), P53, MDA, GST, SOD, zinc and vitamin C in 35 wheat milling workers and 40 control subjects.Results: Statistical analysis revealed that ALT, AST, GGT, ALP, P53, MDA, GST and SOD in workers were significantly elevated compared to their controls. In the milling workers, there were significant correlations between MDA levels and the levels of AST, GGT, and P53, while, P53 was inversely correlated with GST and SOD activities. There were significant correlations between Zn levels and GGT, GST and SOD activities, between vitamin C and GST activities, and vitamin C inversely correlated with MDA. Conclusion:The present study concluded that the oxidative stress of AFB1 elevated the MDA and the liver enzymes in wheat milling workers. GST has a crucial role in the detoxification of aflatoxin and SOD as a scavenger antioxidant increased in the workers to overcome the oxidative toxic effects of AFB1 on the liver of the workers, and roles of Zn and vitamin C were significant in activation of these processes.

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Integrated analysis of transcriptomics and metabonomics profiles in aflatoxin B1-induced hepatotoxicity in rat

Cited by 68 publications

References 50 publications

The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice

The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies

Oxidative Role of Aflatoxin B1 on the Liver of Wheat Milling Workers

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