Cytotoxic effects induced by patulin, sterigmatocystin and beauvericin on CHO–K1 cells

Zouaoui, Nidhal; Mallebrera, Beatriz; Berrada, Houda; Abid‐Essefi, Salwa; Bacha, Hassen; Ruiz, María-José

doi:10.1016/j.fct.2016.01.010

Cited by 56 publications

(22 citation statements)

References 42 publications

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“…Thus, GSH levels could be depleted by both toxins and decrease the uptake ratio of CYN, inducing the antagonistic effect observed. As Zouaoui et al pointed out, the type of interactions among toxins could be related with the different chemical structures and properties and the competition or not for the same cell receptor, being necessary to investigate the cyanotoxins mechanisms of action when they are alone or in combination.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and morphological effects of microcystin‐LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2

Gutiérrez-Praena

Guzmán-Guillén

Pichardo

et al. 2018

Environmental Toxicology

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Cylindrospermopsin (CYN) and Microcystin-LR (MC-LR) are toxins produced by different cyanobacterial species, which are found mainly in freshwater reservoirs. Both of them can induce, separately, toxic effects in humans and wildlife. However, little is known about the toxic effects of the combined exposure, which could likely happen, taking into account the concomitant occurrence of the producers. As both cyanotoxins are well known to induce hepatic damage, the human hepatocellular HepG2 cell line was selected for the present study. Thus, the cytotoxicity of both pure cyanotoxins alone (0-5 μg/mL CYN and 0-120 μg/mL MC-LR) and in combination for 24 and 48 h was assayed, as long as the cytotoxicity of extracts from CYN-producing and nonproducing cyanobacterial species. The potential interaction of the combination was evaluated by the isobologram or Chou-Talalay's method, which provides a combination index as a quantitative measure of the two cyanotoxins interaction's degree. Moreover, a morphological study of the individual pure toxins and their combinations was also performed. Results showed that CYN was the most toxic pure cyanotoxin, being the mean effective concentrations obtained ≈4 and 90 μg/mL for CYN and MC-LR, respectively after 24 h. However, the simultaneous exposure showed an antagonistic effect. Morphologically, autophagy, at low concentrations, and apoptosis, at high concentrations were observed, with affectation of the rough endoplasmic reticulum and mitochondria. These effects were more pronounced with the combination. Therefore, it is important to assess the toxicological profile of cyanotoxins combinations in order to perform more realistic risk evaluations.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic and morphological effects of microcystin‐LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2

Gutiérrez-Praena

Guzmán-Guillén

Pichardo

et al. 2018

Environmental Toxicology

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“…Our previous work found that dead insect extracts cannot induce extra production of NRPs, further supporting the above inference that the immunity of live host insects stimulating I. cicadae produces high levels of NRPs (Luo et al, ). Despite the lack of the acute toxicity, some of these NRPs, such as the beauvericins and enniatins, showed toxicity to mammalian cells (Molnar, Gibson, & Krasnoff, ; Wang & Xu, ; Zouaoui et al, ). Clearly, the insect portions that contain high levels of NRPs may have more potential safety issues than the coremia (WC and CC) and CM.…”

Section: Resultsmentioning

confidence: 99%

Metabolomic variation in wild and cultured cordyceps and mycelia of Isaria cicadae

Zhang

Fan

et al. 2019

Biomedical Chromatography

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Isaria cicadae is one of the fungi used in traditional Chinese medicine with the longest tradition. It is used not only as a herbal medicine but also as a health food in Asia, together with cultured cordyceps and mycelia of the fungus used as substitute. However, the differences in their metabolite are unknown. Using a high‐performance liquid chromatography–mass spectrometry (HPLC–MS)‐based metabolomic method, we found that the fungus varies in its metabolism during growth on wild insects, artificially raised insects and artificial medium. There were 109 discriminatory metabolites detected in the samples by orthogonal projection to latent structure discriminant analysis and one‐way ANOVA. High level of nonribosomal peptides (NRPs) only existed in the insect portions of the wild cordyceps (WI) and cultured cordyceps (CI), revealing that immunostimulation of the host insects enhanced the synthesis of NRPs in the fungus. The finding of a significantly higher level of sphingolipids in both the insect portions (WI, CI) and the coremia of the wild cordyceps (WC) and cultured cordyceps (CC) but not in cultured mycelia (CM) of I. cicadae implies that the immunostimulation of the live insects can induce the fungus to produce more sphingolipids, and this enhanced ability is probably heritable. Apart from NRPs and sphingolipids, the insect portions also contained higher levels of bioactive compounds such as lateritin, anisomycin, streptimidone and ustiloxins. In contrast, the coremium groups (WC, CC) and CM contained 10‐fold less NRP but much higher levels of sanative metabolites such as tocotrienol, 3′‐deoxy‐hanasanagin, γ‐aminobutyric acid and phospholipids than the insect portions. The significantly higher content of antioxidants in WC, CC and CM than in WI and CI suggests that environmental oxygen has a significant effect on the metabolites. The temperature stress which the wild cordyceps encounters during growth is responsible for the relatively high content of trehalose. These findings indicate that the immunity of the host insect and growth environment have a strong impact on the metabolomic variation in Isaria cicadae. The variation in metabolites suggests differential utilization value for the insect portions, coremia and mycelia of the fungus.

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“…Similarly to Loewe's additivity model, the isobologram can be constructed. The Chou-Talalay model combined with an isobologram has been applied in the majority of the recently published studies [39,[51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] listed in Table 2. Its great advantage is the recent development of a method for the estimation of confidence intervals for the combination index which enables the application of statistics [66].…”

Section: Chou and Talalay's Median Effect Approachmentioning

confidence: 99%

Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?

Kifer

Jakšić

Klarić

2020

Toxins

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In the past decades, many studies have examined the nature of the interaction between mycotoxins in biological models classifying interaction effects as antagonisms, additive effects, or synergisms based on a comparison of the observed effect with the expected effect of combination. Among several described mathematical models, the arithmetic definition of additivity and factorial analysis of variance were the most commonly used in mycotoxicology. These models are incorrectly based on the assumption that mycotoxin dose-effect curves are linear. More appropriate mathematical models for assessing mycotoxin interactions include Bliss independence, Loewe’s additivity law, combination index, and isobologram analysis, Chou-Talalays median-effect approach, response surface, code for the identification of synergism numerically efficient (CISNE) and MixLow method. However, it seems that neither model is ideal. This review discusses the advantages and disadvantages of these mathematical models.

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Cytotoxic effects induced by patulin, sterigmatocystin and beauvericin on CHO–K1 cells

Cited by 56 publications

References 42 publications

Cytotoxic and morphological effects of microcystin‐LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2

Cytotoxic and morphological effects of microcystin‐LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2

Metabolomic variation in wild and cultured cordyceps and mycelia of Isaria cicadae

Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?

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