Heme oxygenase-1 regulates autophagy through carbon–oxygen to alleviate deoxynivalenol-induced hepatic damage

Zhao, Peng; Liao, Yixiang; Wang, Xiaoqian; Chen, Liangkai; Wang, Liangliang; Qin, Chenyuan; Wang, Zhenting; Cai, Mengyao; Hu, Jiawei; Li, Dan; Yao, Ping; Nüssler, Andreas K.; Liu, Liegang; Yang, Wei

doi:10.1007/s00204-019-02649-6

Cited by 25 publications

(12 citation statements)

References 46 publications

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“…This observation is in line with other research studies presenting DON-induced autophagy in cells (Gu et al 2019;Wang et al 2020). As reported by Peng et al DONinduced apoptosis is associated with increased expression of caspase 3 (Peng et al 2020) and increased expression of Bax (Hou et al 2021). The observed in PNT1A cells apoptosis was associated with modulation of the expression of Bax and caspase 3 similarly to previous studies.…”

Section: Discussionsupporting

confidence: 92%

Deoxynivalenol induces apoptosis and autophagy in human prostate epithelial cells via PI3K/Akt signaling pathway

et al. 2021

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Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most deregulated signaling pathway in prostate cancer. It controls basic processes in cells: cell proliferation and death. Any disturbances in the balance between cell death and survival might result in carcinogenesis. Deoxynivalenol (DON) is one of the most common mycotoxins, a toxic metabolites of fungi, present in our everyday diet and feed. Although previous studies reported DON to induce oxidative stress, modulate steroidogenesis, DNA damage and cell cycle modulation triggering together its toxicity, its effect on normal prostate epithelial cells is not known. The aim of the study was to evaluate the effect of DON on the apoptosis and autophagy in normal prostate epithelial cells via modulation of PI3K/Akt signaling pathway. The results showed that DON in a dose of 30 µM and 10 µM induces oxidative stress, DNA damage and cell cycle arrest in G2/M cell cycle phase. The higher concentration of DON induces apoptosis, whereas lower one autophagy in PNT1A cells, indicating that modulation of PI3K/Akt by DON results in the induction of autophagy triggering apoptosis in normal prostate epithelial cells.

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Section: Discussionsupporting

confidence: 92%

Deoxynivalenol induces apoptosis and autophagy in human prostate epithelial cells via PI3K/Akt signaling pathway

et al. 2021

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“…A previous study found that the chemical silencing of HO-1 by zinc protoporphyrin (ZnPP) can exacerbate inflammation, oxidative stress, hepatocyte apoptosis, and liver damage [ 20 ]. In addition, the HO-1 system can protect the liver from ischemia/reperfusion injury by enhancing autophagy [ 21 , 22 ]. Our previous study also observed that HO-1 could reduce DON-induced oxidative stress in human primary lymphocytes [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Heme Oxygenase-1 on Liver Injury Caused by DON-Induced Oxidative Stress and Cytotoxicity

Meng

Wang

Liao

et al. 2021

Toxins

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Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. Oxidative stress and DNA damage play a critical role in the toxicity of DON. However, previous studies focused more on acute toxicity in vivo/vitro models and lacked subchronic toxicity study in vivo. The potentially harmful effect of DON given at doses comparable to the daily human consumption in target organs, especially the liver, which is the main detoxification organ of DON, is also still not fully understood. Otherwise, Heme Oxygenase-1 (HO-1) has also reduced cell damage under the DON condition according to our previous study. Therefore, we used a rodent model that mimicked daily human exposure to DON and further explored its mechanism of toxic effects on liver tissue and Hepa 1–6 cell line. We also used adeno-associated virus (AAV)-modified HO-1 expressing by tail vein injection and constructed lentivirus-Hepa 1–6 cell line for mimicking HO-1 protective ability under the DON condition. The main results showed that both 30 d and 90 d exposures of DON could cause low-grade inflammatory infiltration around hepatic centrilobular veins. The reactive oxygen species (ROS) and 8-hydroxy-2 deoxyguanosine (8-OHdG) increased during DON exposure, indicating oxidation stress and DNA damage. Significantly, AAV-mediated liver-specific overexpression of HO-1 reduced DON-induced liver damage and indirectly protected the abilities of antioxidant enzyme/DNA damage repair system, while AAV-mediated silence of HO-1 produced the opposite effect. In addition, we found that overexpression of HO-1 could enhance autophagy and combined it with an antioxidant enzyme/DNA damage repair system to inhibit DON-induced hepatocyte damage. Altogether, these data suggest that HO-1 reduces the oxidative stress and DNA damage caused by DON sub-chronic exposure through maintaining DNA repair, antioxidant activity, as well as autophagy.

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“…Ndlovu et al (2021) reported that DON (26.17 μmol/L) can cause oxidative stress and downregulate Nrf2-induced cytoprotection by suppressing the antioxidant signaling mechanism in HepG2 cells. Peng et al (2020) first demonstrated that estimated human daily DON exposure (25 mg/kg bw) for 30 and 90 days caused low-grade inflammatory infiltration around the hepatic centrilobular vein as well as impaired liver function. DON can also activate autophagy and apoptosis at the molecular level and increase the expression of autophagy-related proteins as well as cleaved caspase-3 and caspase-7.…”

Section: Hepatotoxicitymentioning

confidence: 99%

Global distribution, toxicity to humans and animals, biodegradation, and nutritional mitigation of deoxynivalenol: A review

Liu

Cai

et al. 2023

Comp Rev Food Sci Food Safe

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Deoxynivalenol (DON) is one of the main types of B trichothecenes, and it causes health‐related issues in humans and animals and imposes considerable challenges to food and feed safety globally each year. This review investigates the global hazards of DON, describes the occurrence of DON in food and feed in different countries, and systematically uncovers the mechanisms of the various toxic effects of DON. For DON pollution, many treatments have been reported on the degradation of DON, and each of the treatments has different degradation efficacies and degrades DON by a distinct mechanism. These treatments include physical, chemical, and biological methods and mitigation strategies. Biodegradation methods include microorganisms, enzymes, and biological antifungal agents, which are of great research significance in food processing because of their high efficiency, low environmental hazards, and drug resistance. And we also reviewed the mechanisms of biodegradation methods of DON, the adsorption and antagonism effects of microorganisms, and the different chemical transformation mechanisms of enzymes. Moreover, nutritional mitigation including common nutrients (amino acids, fatty acids, vitamins, and microelements) and plant extracts was discussed in this review, and the mitigation mechanism of DON toxicity was elaborated from the biochemical point of view. These findings help explore various approaches to achieve the best efficiency and applicability, overcome DON pollution worldwide, ensure the sustainability and safety of food processing, and explore potential therapeutic options with the ability to reduce the deleterious effects of DON in humans and animals.

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Heme oxygenase-1 regulates autophagy through carbon–oxygen to alleviate deoxynivalenol-induced hepatic damage

Cited by 25 publications

References 46 publications

Deoxynivalenol induces apoptosis and autophagy in human prostate epithelial cells via PI3K/Akt signaling pathway

Deoxynivalenol induces apoptosis and autophagy in human prostate epithelial cells via PI3K/Akt signaling pathway

The Protective Effect of Heme Oxygenase-1 on Liver Injury Caused by DON-Induced Oxidative Stress and Cytotoxicity

Global distribution, toxicity to humans and animals, biodegradation, and nutritional mitigation of deoxynivalenol: A review

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