Aflatoxin B1 impairs mitochondrial functions, activates ROS generation, induces apoptosis and involves Nrf2 signal pathway in primary broiler hepatocytes

Liu, Yan; Wang, Wenjun

doi:10.1111/asj.12550

Cited by 121 publications

(90 citation statements)

References 32 publications

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“…In primary broiler hepatocytes, AFB1 caused increased mitochondrial ROS production, decreased mitochondrial membrane potential and induced apoptosis. This was associated with upregulated mRNA expression of Nrf2, but downregulated mRNA expressions of NAD(P)H: quinine oxidoreductase 1, SOD and HO-1 [264]. Similar changes in Nrf2 expression due to the exposure to AFB1 were also observed in broiler cardiomyocytes [265].…”

Section: Mycotoxinssupporting

confidence: 57%

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.

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Section: Mycotoxinssupporting

confidence: 57%

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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“…Previous studies have reported critical roles of ROS in mycotoxin‐induced cell apoptosis . Here, we further investigated the potential involvement of ROS generation in ENN B1‐associated apoptosis of blastocysts.…”

Section: Resultsmentioning

confidence: 95%

Enniatin B1 exerts embryotoxic effects on mouse blastocysts and induces oxidative stress and immunotoxicity during embryo development

Huang

Wang

Chan

2018

Environmental Toxicology

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“…A recent study showed that the AFB1 treatment resulted in a significant and concentration-dependent increase in intracellular ROS production, whereas mitochondrial functions such as glutamate/malate and succinate-driven respiration were significantly uncoupled. Those oxidative stress effects activated mitochondrial ROS-dependent signal pathways, which induced apoptosis through the mitochondrial signal pathway [77]. What's more, there are some proteins modulated by AFB1 like CYP1A2, CYP1A5, CYP3A4, TP53, GSMT1, MDM2, CAT, OGG1, IRS1, IRS2, SRC, AKT1, MAPK1, MAPK3, and PDK1.…”

Section: The Metabolism and Toxic Mechanism Of Afb1mentioning

confidence: 99%

The Toxic Effects of Aflatoxin B1: An Update

Shan¹

2020

Aflatoxin B1 Occurrence, Detection and Toxicological Effects

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Aflatoxin B1 (AFB1) is the most toxic in aflatoxin family. It is well known for its involvement in hepatic carcinogenesis. Other adverse effects include immune weakness, reproduction deficiency, malnutrition, and growth impairment. The key mechanism of AFB1 carcinogenesis is supposed to be epoxidation, which produce the AFB1-8,9-epoxide (AFBO) strongly adductive to DNA molecules. Other metabolites like AFM1, AFH1, and AFL, which retain DNA adductive capability, extend its toxicity. Scientists now found that AFB1 also affected epigenetic regulation, which might shed new light into AFB1 toxicity mechanism researches. The detoxification of AFB1 has always been a hot spot in AFB1-related studies. The major methods can be categorized into physical treatment, biological treatment, chemical treatment, combination strategy, and sorbent additives. None of the methods is 100% perfect, however considering economic factors, simplicity, effectiveness, safety, and preservation of the food nutrition. This review will discuss the toxicity and toxic mechanisms of AFB1. Also, detoxification of AFB1 will be reviewed.2 as in the 1970s, its hepatocarcinogenic property has been testified in animal models [5], and there since, several epidemiological studies from Asia and Africa areas monitored intersection of high HCC incidence and AFB1 contamination, with 4.6-28.2% of HCC cases globally attributed to AFB1 exposure [6]. Moreover, hepatitis B virus (HBV) that cooperates with AFB1 can drastically increase the risk of HCC by 30-fold [7]. Recent researches also find evidences that hepatitis C virus (HCV) also has a synergistic role with AFB1 in hepatocarcinogenesis. Jeannot et al. found that the incidence of tumorous or pretumorous lesions was elevated by 2.5-fold in AFB1-treated HCV transgenic mice compared with wild-type mice [8]. Recently, a 20-year clinical follow-up study in Taiwan investigated HCC risk associated with AFB1 exposure in HCV-positive and HBV-HCV-negative individuals. HCV and AFB1 exposure were both found as independent risk factors for HCC development. Elevated serum AFB1albumin adduct levels were significantly associated with an increased risk of HCC newly developed within 8 years of follow-up in non-HBV-non-HCV participants with habitual alcohol consumption [crude OR (95% CI) for high vs. low/undetectable levels, 4.22 (1.16-15.37)], and HCV-infected participants [3.39 (1.31-8.77)], but not in non-HBV-non-HCV participants without alcohol drinking habit. Therefore, it indicated that AFB1 exposure contributes to the development of HCC in participants with significant risk factors for cirrhosis including alcohol and HCV infection [9]. What's more, AFB1 exposure can induce the increased levels of blood glucose in mice and, also, the high probability to develop liver cancer [10].Liver is not the only target organ of AFB1 toxification. Its impairment on the immune system has been established in both humans and animals. Several studies linked AFB1 exposure with reduced levels or functions of immunological factors, such as de...

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Aflatoxin B1 impairs mitochondrial functions, activates ROS generation, induces apoptosis and involves Nrf2 signal pathway in primary broiler hepatocytes

Cited by 121 publications

References 32 publications

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Enniatin B1 exerts embryotoxic effects on mouse blastocysts and induces oxidative stress and immunotoxicity during embryo development

The Toxic Effects of Aflatoxin B1: An Update

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