In Vitro Evaluation of the Individual and Combined Cytotoxic and Estrogenic Effects of Zearalenone, Its Reduced Metabolites, Alternariol, and Genistein

Balázs, Adrienn; Faisal, Zelma; Csepregi, Rita; Kőszegi, Tamás; Kriszt, Balázs; Szabó, István; Poór, Miklós

doi:10.3390/ijms22126281

Cited by 19 publications

(8 citation statements)

References 69 publications

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“…Furthermore, hidden ZEN might have been formed after 5 days by non-covalent interactions with matrix constituents, reducing extraction efficiency and thus resulting in a decreased detection of ZEN. This phenomenon has already been observed in maize, where ZEN can bind to the main protein, zein, due to the formation of hydrogen bonds and hydrophobic and electrostatic interactions [ 47 ]. Although similar observations for wheat are not yet available in the literature, this might have played a role in our experiment.…”

Section: Resultsmentioning

confidence: 80%

Actinobacteria as Promising Biocontrol Agents for In Vitro and In Planta Degradation and Detoxification of Zearalenone

De Troyer,

De Zutter,

De Saeger

et al. 2024

Toxins

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Zearalenone (ZEN) is a prevalent mycotoxin found in grains and grain-derived products, inducing adverse health effects in both animals and humans. The in-field application of microorganisms to degrade and detoxify ZEN is a promising strategy to enhance the safety of food and feed. In this study, we investigated the potential of three actinobacterial strains to degrade and detoxify ZEN in vitro and in planta on wheat ears. The residual ZEN concentration and toxicity in the samples were analysed with UHPLC-MS/MS and a bioluminescence BLYES assay, respectively. Streptomyces rimosus subsp. rimosus LMG19352 could completely degrade and detoxify 5 mg/L ZEN in LB broth within 24 h, along with significant reductions in ZEN concentration both in a minimal medium (MM) and on wheat ears. Additionally, it was the only strain that showed a significant colonisation of these ears. Rhodococcus sp. R25614 exhibited partial but significant degradation in LB broth and MM, whereas Streptomyces sp. LMG16995 degraded and detoxified ZEN in LB broth after 72 h by 39% and 33%, respectively. Although all three actinobacterial strains demonstrated the metabolic capability to degrade and detoxify ZEN in vitro, only S. rimosus subsp. rimosus LMG19352 showed promising potential to mitigate ZEN in planta. This distinction underscores the importance of incorporating in planta screening assays for assessing the potential of mycotoxin-biotransforming microorganisms as biocontrol agents.

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Section: Resultsmentioning

confidence: 80%

Actinobacteria as Promising Biocontrol Agents for In Vitro and In Planta Degradation and Detoxification of Zearalenone

De Troyer,

De Zutter,

De Saeger

et al. 2024

Toxins

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“…Upon 48-h incubation with AOH, an onset of cytotoxicity was observed at concentrations ≥ 5 μM in Ishikawa cells (Aichinger et al 2020b ). In HeLa cells exposed to 0–250 µM AOH for 24 h (in the absence of FBS to avoid interference), a concentration-dependent decrease in ATP levels was shown with a significant decrease noticed at 10 µM, and an IC 50 of 33.6 µM (Balázs et al 2021 ). Using the Alamar blue (AB) and MTT assays in the human adrenocortical carcinoma cell line H295R, exposed for 48 h to 0.1–1000 ng/mL, AOH had no effect.…”

Section: Cytotoxicitymentioning

confidence: 99%

Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health

Louro,

Vettorazzi,

López de Cerain

et al. 2023

Arch Toxicol

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Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.

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“…EGCG is known to suppress the activation of both classical NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasomes and caspase-11-mediated non-classical inflammasomes via the TLR4/NF-κB pathway, thereby effectively exerting its anti-inflammatory properties ( 80 ). Genistein (Gen), a compound derived from Soybean isoflavone (SIF) ( 84 ), has been shown to improve memory abilities in patients with AD and to attenuate inflammation in Aβ 25-35 -induced BV-2 microglia through inhibition of the TLR4/NF-κB signaling pathway. These findings suggest that a diet rich in plant-derived Gen may be beneficial in reducing the risk of AD by alleviating inflammation ( 81 ).…”

Section: Nf-κb and Mapk Signaling Pathwaysmentioning

confidence: 99%

Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review)

Zheng,

Zhang,

Zhang

et al. 2023

Int J Mol Med

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The intricate nature of Alzheimer's disease (AD) pathogenesis poses a persistent obstacle to drug development. In recent times, neuroinflammation has emerged as a crucial pathogenic mechanism of AD, and the targeting of inflammation has become a viable approach for the prevention and management of AD. The present study conducted a comprehensive review of the literature between October 2012 and October 2022, identifying a total of 96 references, encompassing 91 distinct pharmaceuticals that have been investigated for their potential impact on AD by inhibiting neuroinflammation. Research has shown that pharmaceuticals have the potential to ameliorate AD by reducing neuroinflammation mainly through regulating inflammatory signaling pathways such as NF-κB, MAPK, NLRP3, PPARs, STAT3, CREB, PI3K/Akt, Nrf2 and their respective signaling pathways. Among them, tanshinone IIA has been extensively studied for its anti-inflammatory effects, which have shown significant pharmacological properties and can be applied clinically. Thus, it may hold promise as an effective drug for the treatment of AD. The present review elucidated the inflammatory signaling pathways of pharmaceuticals that have been investigated for their therapeutic efficacy in AD and elucidates their underlying mechanisms. This underscores the auspicious potential of pharmaceuticals in ameliorating AD by impeding neuroinflammation.

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In Vitro Evaluation of the Individual and Combined Cytotoxic and Estrogenic Effects of Zearalenone, Its Reduced Metabolites, Alternariol, and Genistein

Cited by 19 publications

References 69 publications

Actinobacteria as Promising Biocontrol Agents for In Vitro and In Planta Degradation and Detoxification of Zearalenone

Actinobacteria as Promising Biocontrol Agents for In Vitro and In Planta Degradation and Detoxification of Zearalenone

Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health

Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review)

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