Molecular Mechanism of Aflatoxin-Induced Hepatocellular Carcinoma Derived from a Bioinformatics Analysis

Cai, Peirong; Zheng, Hao; She, Jinjin; Feng, Na; Zou, Hui; Gu, Jianhong; Yuan, Yan; Liu, Zongping; Bian, Jianchun

doi:10.3390/toxins12030203

Cited by 19 publications

(13 citation statements)

References 49 publications

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“…Dysfunction of cell repairing mechanisms that can result in: tissue necrosis, as for example by sulfasalazine, ketoconazole, or valproic acid ( Kleiner, 2017 ); in fibrosis, by e.g., chronic exposure to methotrexate, high doses of retinol (vitamin A), and iron intoxication ( Zhang et al, 2016 ); or in carcinogenesis, as a consequence of aflatoxin B1 exposure ( Gregus, 2013 ; Jaeschke, 2013 ; Cai et al, 2020 );…”

Section: Drug-induced Hepatotoxicity: Overview Liver Metabolism and mentioning

confidence: 99%

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

Serras

Rodrigues

Cipriano

et al. 2021

Front. Cell Dev. Biol.

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The poor predictability of human liver toxicity is still causing high attrition rates of drug candidates in the pharmaceutical industry at the non-clinical, clinical, and post-marketing authorization stages. This is in part caused by animal models that fail to predict various human adverse drug reactions (ADRs), resulting in undetected hepatotoxicity at the non-clinical phase of drug development. In an effort to increase the prediction of human hepatotoxicity, different approaches to enhance the physiological relevance of hepatic in vitro systems are being pursued. Three-dimensional (3D) or microfluidic technologies allow to better recapitulate hepatocyte organization and cell-matrix contacts, to include additional cell types, to incorporate fluid flow and to create gradients of oxygen and nutrients, which have led to improved differentiated cell phenotype and functionality. This comprehensive review addresses the drug-induced hepatotoxicity mechanisms and the currently available 3D liver in vitro models, their characteristics, as well as their advantages and limitations for human hepatotoxicity assessment. In addition, since toxic responses are greatly dependent on the culture model, a comparative analysis of the toxicity studies performed using two-dimensional (2D) and 3D in vitro strategies with recognized hepatotoxic compounds, such as paracetamol, diclofenac, and troglitazone is performed, further highlighting the need for harmonization of the respective characterization methods. Finally, taking a step forward, we propose a roadmap for the assessment of drugs hepatotoxicity based on fully characterized fit-for-purpose in vitro models, taking advantage of the best of each model, which will ultimately contribute to more informed decision-making in the drug development and risk assessment fields.

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Section: Drug-induced Hepatotoxicity: Overview Liver Metabolism and mentioning

confidence: 99%

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

Serras

Rodrigues

Cipriano

et al. 2021

Front. Cell Dev. Biol.

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“…Hepatocellular carcinoma (HCC) is the sixth most common tumor and the fourth leading cause of cancer-associated death worldwide (Bray et al, 2018) and accounts for 80 -90 % of all main liver cancers (Vogel et al, 2018). Many factors cause cirrhosis that increases the risk of HCC (Fong et al, 2010) as viral infection with the hepatitis B or hepatitis C (Arzumanyan et al, 2013), alcoholism (Scoccianti et al, 2016), congenital metabolic diseases, diabetes, and smoking (Chuang et al, 2009) along with exposure to carcinogenic compounds as aflatoxins (Cai et al, 2020). This is a set of mycotoxins created by the Aspergillus flavus in cereals like corn and peanuts due to storage in warm and moist and is a…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Effect of Myrrh (Commiphora molmol) and Doxorubicin on Diethylnitrosamine Induced Hepatocarcinogenesis in Male Albino Rats

Anwar

Moghazy

Osman

et al. 2021

Asian Pac J Cancer Prev

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Background: This study was conducted to assess the therapeutic effect of Myrrh on Diethylnitrosamine (DEN)induced hepatocarcinogenesis (HCC) in male albino rats. Methods: Fifty male albino rats were divided into five groups (10 rats each). Group 1 (control group) received distilled water. Group 2 (positive control) was injected intraperitoneally with DEN (55 mg/kg b.w) twice a week for two weeks, while group 3 (DOX) received doxorubicin i.p (10 mg/ kg b.w) after concomitant with DEN twice a week for four weeks. Groups 4 and 5 received a low dose of Myrrh (250 mg/kg b.w) and a high dose of Myrrh (500 mg/kg b.w) respectively daily for four weeks after the induction with DEN. The sera were used to estimate the liver enzymes (ALT, AST, and ALP), Alpha-fetoprotein (AFP), Total antioxidant capacity (TAC), and Tumor necrosis factor-ἁ (TNF-ἁ). Also, the liver tissues were collected to determine the oxidative stress markers in addition to the histopathological and immunohistochemical investigations. Results: The results showed that the induction of DEN causes a significant increase in the level of liver enzymes (ALT, AST, and ALP), AFP and TNF-ἁ as well as produce oxidative stress indicated by increasing of malondialdehyde (MDA) with the reduction in TAC and glutathione (GSH). Meanwhile, there are noticeable histopathological lesions with loss of hepatic architecture. This was accompanied by a significant increase of immunohistochemical markers; Caspase-3, vascular endothelial growth factor (VEGF), transforming growth factor β1(TGF-β1), and carcinoembryonic antigen (CEA) percentage area. The treatment of DEN rats with DOX reduced the alterations in most parameters. A marked amelioration of all parameters in a dose-dependent manner of Myrrh to the values almost near to those of the control group. Conclusion: Our data revealed that Water extract of Myrrh (C. molmol) has a potential therapeutic effect in attenuation of HCC induced DEN.

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“…The Disruption of Circadian Rhythms as a Risk Factor for HCC. Chronic infection with hepatitis virus, exposure to carcinogens (e.g., aflatoxin-contaminated foodstuffs), and diabetes are all risk factors for HCC [92][93][94][95]. These risk factors are also related to the disruption of circadian rhythms.…”

Section: The Function and Mechanisms Of Circadianmentioning

confidence: 99%

The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

Jiang

Shen

Fasae

et al. 2021

Oxidative Medicine and Cellular Longevity

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Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

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Molecular Mechanism of Aflatoxin-Induced Hepatocellular Carcinoma Derived from a Bioinformatics Analysis

Cited by 19 publications

References 49 publications

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies

The Therapeutic Effect of Myrrh (Commiphora molmol) and Doxorubicin on Diethylnitrosamine Induced Hepatocarcinogenesis in Male Albino Rats

The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

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