Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Salem, Intidhar Ben; Prola, Alexandre; Boussabbeh, Manel; Guilbert, Arnaud; Bacha, Hassen; Abid‐Essefi, Salwa; Lemaire, Christophe

doi:10.1007/s12192-015-0613-0

Cited by 68 publications

(53 citation statements)

References 62 publications

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“…Transcriptional activation of CHOP plays an important role in ER stress-induced apoptosis in cells [34]. Furthermore, a prior study reported similar data in human colon HCT116 cells and human kidney HEK293 cells [35]. In this cell culture study, ZEN induced ER stress and ER stress-mediated cell death through the CHOP pathway.…”

Section: Discussionsupporting

confidence: 74%

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Yoon

Lee²,

Seok

et al. 2019

Toxins

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Zearalenone (ZEN) is a mycotoxin produced by Fusarium species; however, its mechanisms of action in human livers have not been fully elucidated. Thus, we investigated the toxic mechanisms of ZEN in human liver cells. HepG2 cells were treated with ZEN (0–40 μg/mL) for up to 24 h. A significant decrease in cell viability was observed after treatment with 20 and 40 μg/mL of ZEN, including a significant increase in apoptosis and reactive oxygen species production. ZEN increased GRP78 and CHOP, and eIF2α phosphorylation, indicating ER stress; elevated transcription of the autophagy-associated genes, beclin1 and LC3, and translation of LC3; and increased phase I metabolism by increasing PXR and CYP3A4. The protein expression level of CYP3A4 was higher with ZEN treatment up to 20 μg/mL, but remained at the control level after treatment with 40 μg/mL ZEN. In phase II metabolism, Nrf2 activation and UGT1A expression were increased with ZEN treatment up to 20 μg/mL. Treating cells with an ER stress inhibitor alleviated ZEN-induced cell death and autophagy, and inhibited the expression of phase I/II enzymes. Overall, high ZEN concentrations can modulate the expression of phase I/II enzymes via ER stress and reduced protein levels in human liver cells.

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Section: Discussionsupporting

confidence: 74%

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Yoon

Lee²,

Seok

et al. 2019

Toxins

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“…Previous studies have shown that the ER stress pathway has been reported to participate in oxidative damage and apoptosis induced by ZEN 22 – 24 , 46 . To provide further evidence that the A2 fermentation broth exerts a protective effect from ZEN-induced kidney injury, we explored whether the A2 fermentation broth could decrease both ER stress and apoptosis induced by ZEN.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, ZEN could alter the enzymatic and hematological parameters of mice, and it could induce higher levels of oxidative stress 19 – 21 . Meanwhile, ZEN-induced apoptosis is characterized by ROS production and increased lipid peroxidation 22 , 23 . A previous study demonstrated that ZEN induced apoptosis in RAW 264.7 macrophages through endoplasmic reticulum stress (ER stress) 24 .…”

Section: Introductionmentioning

confidence: 99%

Bacillus velezensis A2 fermentation exerts a protective effect on renal injury induced by Zearalenone in mice

Wang

Pan

et al. 2018

Sci Rep

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Zearalenone (ZEN) is an estrogen-like mycotoxin occurring in food and feeds, and it can cause oxidative damage and apoptosis in the testis, liver, and kidney. A current concern for researchers is how to reduce the harm it causes to humans and animals. In this study, our aim was to isolate and identify a novel and efficient ZEN-detoxifying strain of bacteria, and we aimed to assess the protective effect of the isolated strain on kidney damage caused by ZEN in mice. Our results indicated that a strain of Bacillus velezensis (B. velezensis), named A2, could completely degrade ZEN (7.45 μg/mL) after three days of incubation at 37 °C in the Luria-Bertani (LB) medium. This fermentation broth of the B. velezensis A2 strain was given to mice. The histopathological analysis indicated that the fermentation broth from the B. velezensis A2 strain reduced the degree of renal injury that is induced by ZEN. Furthermore, it greatly reduced the increase in serum levels of creatinine (CRE), uric acid (UA), and urea nitrogen (BUN) caused by ZEN. In addition, B. velezensis A2 strain also significantly inhibited the increase of malonaldehyde (MDA) content, and reversed the decreases of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities caused by ZEN. Studies have shown that ZEN is involved in the regulation of mRNA and protein levels of genes involved in the ER stress-induced apoptotic pathway, such as heavy chain binding protein (BIP), C-/-EBP homologous protein (CHOP), cysteine Aspartate-specific protease-12 (Caspase-12), c-Jun N-terminal kinase (JNK), and BCL2-related X protein (Bcl-2 and Bax). However, when mice were administered the fermentation broth of the B. velezensis A2 strain, it significantly reversed the expressions of these genes in their kidney tissue. In conclusion, our results indicate that the newly identified strain of B. velezensis A2, has a protective effect from renal injury induced by ZEN in mice. This strain has a potential application in the detoxification of ZEN in feed and protects animals from ZEN poisoning.

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“…Lipoic acid and vitamin C were evaluated in vivo in terms of their abilities to alleviate the liver oxidative damage induced by AFB1 or ZEA, and vitamin C was found to alleviate the damage via regulating the nuclear receptor signaling pathway with changes of nuclear receptor genes (PXR, constitutive active receptor [CAR]) (Ma et al., ; Shi et al., ). Crocin with a high antioxidant capacity was found to protect HEK293 cells and human colon carcinoma (HCT116) cells against apoptosis and endoplasmic reticulum stress induced by ZEA and its 2 metabolites (Ben Salem et al., , ). Carotenoids such as lycopene were found to exhibit protection against ZEA‐induced oxidative stress, inflammatory and reproductive damages, and OTA‐induced DNA damage in male mice (Aydin et al., ; Boeira et al., ).…”

Section: Food Compounds Especially Those Of Plant Origin For Prevenmentioning

confidence: 99%

The Significance of Regulatory MicroRNAs: Their Roles in Toxicodynamics of Mycotoxins and in the Protection Offered by Dietary Therapeutics Against Mycotoxin‐Induced Toxicity

Xue

Sun‐Waterhouse

Wang

et al. 2018

Comp Rev Food Sci Food Safe

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Mycotoxins are contaminants commonly found in foods and represent a worldwide threat to human health and welfare. Efforts have been undertaken to reduce mycotoxins and their toxicity, including the introduction of good agricultural practices, appropriate food processing, specific biotransformation approaches, and pursue therapeutic agents to counteract mycotoxins. Efficient and predictive tools are required for investigations on mycotoxins and their toxicodynamics, and strategies for mycotoxin reduction. Gene expression and transcriptome analysis can unravel the mode of action, transformation and combined toxicity of mycotoxins, or mycotoxin's interactions with food components including dietary therapeutics, at the cellular level and from a molecular perspective. MicroRNAs (miRNAs) regulate endogenously and posttranscriptionally the expression of target genes and enzymes involved in physiological, disease and toxicological responses, and the metabolism of therapeutic agents. Accordingly, this review aimed to collect up‐to‐date information on (1) the regulatory role of miRNAs in mycotoxin‐initiated toxicological processes and (2) the protective role of active ingredients from plants on mycotoxin‐induced toxicity. Through such a review of published evidence, we found some common signal pathways involving miRNAs shared by these two types of biological events. This finding indicates the possibility of using miRNAs as biomarkers in assessing and controlling mycotoxins in food via cellular mechanisms.

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Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Cited by 68 publications

References 62 publications

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Bacillus velezensis A2 fermentation exerts a protective effect on renal injury induced by Zearalenone in mice

The Significance of Regulatory MicroRNAs: Their Roles in Toxicodynamics of Mycotoxins and in the Protection Offered by Dietary Therapeutics Against Mycotoxin‐Induced Toxicity

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