In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells

Heussner, Alexandra H.; Dietrich, Daniel R.; O'Brien, Evelyn

doi:10.1016/j.tiv.2005.08.003

Cited by 104 publications

(69 citation statements)

References 25 publications

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“…At first, this appeared to stand in contrast to literature data including our own earlier findings Heussner et al, 2006;O'Brien et al, 2001). The latter data showed a higher toxicity of OTA compared to that of OTB in various renal cell types, however these data always originated from single time-point short-term investigations.…”

Section: Discussioncontrasting

confidence: 94%

Effects of repeated ochratoxin exposure on renal cells in vitro

Heussner

O'Brien

Dietrich

2007

Toxicology in Vitro

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In the present study an in vitro model of subchronic repeated exposure to OTA and OTB was employed to generate ochratoxinderived subpopulations of human and porcine proximal tubular cells (HKC, IHKE, PKC, LLC-PK1). These cell subpopulations were subsequently used to investigate effects on cell proliferation rates, expression of marker proteins (cytokeratins, vimentin) and the acute cytotoxicity of OTA and OTB (MTT reduction, neutral red uptake, cell number). The hypothesis was tested whether repeated exposure at moderate concentrations of these toxins could provide for a reduced sensitivity of selected cell subpopulations to subsequent toxin exposure. Despite the observed increased cell population doubling times and the reduced sensitivity toward OTA and OTB exposure of some cell types, with the exception of the primary human epithelial cells, no overt changes in the expression of cytokeratin and vimentin could be determined. The presented data, however suggest that repeated exposure of renal epithelial cells to ochratoxins A or B will provide for a subpopulation of cells with reduced ochratoxin-sensitivity and alterations in growth characteristics.

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Section: Discussioncontrasting

confidence: 94%

Effects of repeated ochratoxin exposure on renal cells in vitro

Heussner

O'Brien

Dietrich

2007

Toxicology in Vitro

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“…Recent CIT research is oriented toward nephrotoxicity; both additive and synergistic effects have been described in combination with OTA (ref. 61,[63][64][65] ). With regard to the nephrotoxicity of CIT, the situation may be complicated by the fact that CIT interacts with other naturally occurring mycotoxins e.g.…”

Section: Etiologymentioning

confidence: 99%

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors

Petejová¹,

Martínek²

2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

134

104

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Background and Aims. The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. Methods. A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. Results and Conclusions. Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.

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“…For binary mixtures involving OTA, additive toxic effects were observed for combinations with AFB 1 in kidney cells (Golli-Bennour et al, 2010) and in hepatoma-derived cells (Corcuera et al, 2011), whereas synergistic effects were reported in rat brain glioma, Caco-2 and Vero cells (Creppy et al, 2004); antagonism was described for the combined toxicity of OTA and AFM 1 in Caco-2 cells (Tavares et al, 2013). In addition, synergistic effects between OTA and CIT were identified in renal cells in vitro (Bouslimi et al, 2008;Heussner et al, 2006) and in vivo (Pfohl-Leszkowicz et al, 2008). Recently, the effect of the ternary mixture of OTA, citrinin and sterigmatocystin was explored in a human hepatocellular cancer cell line (Hep3B), showing a synergistic effect at low toxin doses that shifted to antagonism at higher concentrations (Αnninou et al, 2014).…”

Section: Evaluation Of Combined Effects Of Multiple Mycotoxinsmentioning

confidence: 99%

Challenges in risk assessment of multiple mycotoxins in food

Assunção

Silva

Alvito

2016

WMJ

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Most fungi are able to produce several mycotoxins simultaneously and, consequently, to contaminate a wide variety of foodstuffs. Therefore, the risk of human co-exposure to multiple mycotoxins is real, raising a growing concern about their potential impact on human health. Besides, government and industry regulations are usually based on individual toxicities, and do not take into account the complex dynamics associated with interactions between co-occurring groups of mycotoxins. The present work assembles, for the first time, the challenges posed by the likelihood of human co-exposure to these toxins and the possibility of interactive effects occurring after absorption, towards knowledge generation to support a more accurate human risk assessment. Regarding hazard assessment, a physiologically-based framework is proposed in order to infer the health effects from exposure to multiple mycotoxins in food, including knowledge on the bioaccessibility, toxicokinetics and toxicodynamics of single and combined toxins. The prioritisation of the most relevant mixtures to be tested under experimental conditions that attempt to mimic human exposure and the use of adequate mathematical approaches to evaluate interactions, particularly concerning the combined genotoxicity, were identified as the main challenges for hazard assessment. Regarding exposure assessment, the need of harmonised food consumption data, availability of multianalyte methods for mycotoxin quantification, management of left-censored data, use of probabilistic models and multibiomarker approaches are highlighted, in order to develop a more precise and realistic exposure assessment. To conclude, further studies on hazard and exposure assessment of multiple mycotoxins, using harmonised methodologies, are crucial towards an improvement of data quality and a more reliable and robust risk characterisation, which is central for risk management and, consequently, to prevent mycotoxins-associated adverse effects. A deep understanding of the nature of interactions between multiple mycotoxins will contribute to draw real conclusions on the health impact of human exposure to mycotoxin mixtures.

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In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells

Cited by 104 publications

References 25 publications

Effects of repeated ochratoxin exposure on renal cells in vitro

Effects of repeated ochratoxin exposure on renal cells in vitro

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors

Challenges in risk assessment of multiple mycotoxins in food

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