Ochratoxin A at nanomolar concentrations: A signal modulator in renal cells

Gekle, Michael; Sauvant, Christoph; Schwerdt, Gerald

doi:10.1002/mnfr.200400062

Cited by 89 publications

(68 citation statements)

References 87 publications

(101 reference statements)

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“…A review of OTA on renal cells has indicated that glomerular capillaries are damaged by hypertension 38 , which is thought to contribute to OTA-induced disorders. PPARs are closely related to energy status and metabolism.…”

Section: Discussionmentioning

confidence: 99%

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies

Yang

Chen

et al. 2014

Sci Rep

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The mycotoxin ochratoxin A (OTA) is found widely in agricultural commodities. OTA can induce various toxicities. In this study, rats were gavaged with OTA for different weeks. Then, the expression of microRNAs, mRNAs and proteins were measured in the rat livers treated with OTA for 13 weeks. Our sequencing data suggests that the medial and the high doses of OTA exert different effects on livers. Five distinctive pathways were induced after OTA treatment as collectively demonstrated at miRNA, mRNA and protein levels. Two (primary bile acid biosynthesis, and metabolism of xenobiotics by cytochrome P450) are directly associated with liver damage, whereas the remaining pathways (arginine and proline metabolism, cysteine and methionine metabolism, and PPAR signaling pathway) cause metabolic disease. This study reveals OTA-induced early hepatotoxicity for the first time by combining multi-omics methods. The novel metabolic pathways may contribute to the pathogenesis of metabolic diseases later in life.O chratoxin A (OTA) is a low molecular weight mycotoxin produced by certain strains of filamentous fungi of the Aspergillus and Penicillium genera and has been detected in a large variety of agricultural commodities. OTA carries potential health-associated risks and has been classified as a possible human carcinogen (group 2B) by the International Agency for Research on Cancer 1 . OTA has previously been found to induce various toxic effects including nephrotoxicity, hepatotoxicity, immunotoxicity, genotoxicity, carcinogenicity, teratogenicity, neurotoxicity and mutagenicity.The liver is one of the major target organs of OTA biotransformation. Although, some early hepatotoxicity studies employed relative high concentrations of OTA and found remarkable liver lesion 2,3 , lower doses of OTA did not provoke significant pathological changes 4-6 . Most of the previous studies have been extensively focused on OTA-induced kidney damage, less on liver. However, it is still unknown how OTA affects the liver which is the largest detoxification organ of body. Therefore, the identification of early hepatotoxicity can be helpful to understand the mechanism of some diseases that may be developed and progressed by OTA in later stage, and to prevent these diseases in early stage to improve human health.Omics approaches, such as transcriptome and proteome, are promising to detect the pathological changes of liver at a molecular level. Till date, omics technology has been employed only in a few studies to understand the mechanism of OTA hepatotoxicity. Moreover, a high-throughput microarray profiling study on HepG2 liver cell transcriptome demonstrated that multiple hepatic metabolism genes are modulated by OTA exposure 7 . In addition, proteomic approaches have helped identify key proteins in the livers of pigs treated with OTA 8 . These omics approaches have widened our view about OTA hepatotoxicity, however the mechanism of OTA actions remains largely unknown.Recently, microRNAs (miRNAs) in animals and plants are shown to play an impor...

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Section: Discussionmentioning

confidence: 99%

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies

Yang

Chen

et al. 2014

Sci Rep

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“…Indeed, nephrotoxicity is a consequence of acute, sub-acute, but also chronic exposure to OTA. Moreover, exposure to low OTA doses initiates nephrotoxicity (Gekle et al 2005). In this regard, chronic exposure (even to low doses) of OTA seems to be a significant public health problem (Malir et al 2013a).…”

mentioning

confidence: 99%

The occurrence of ochratoxin A in white and parboiled rice

Toman¹,

Malíř²,

Ostrý³

et al. 2016

Czech J. Food Sci.

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“…According to the European survey conducted by Miraglia et al (2), mean plasma concentration of OTA in adults is 0.875 nmol L -1 , and ranges from 0.53 nmol L -1 to 2.75 nmol L -1 . OTA half-life in serum ranges from 120 h in rats to 840 h in monkeys and humans (4,5). This prolonged retention in serum is the consequence of strong binding to serum proteins, mainly to albumin.…”

Section: Ochratoxin A: a Hazardous Mycotoxinmentioning

confidence: 99%

A Journey Through Mitogen-Activated Protein Kinase and Ochratoxin A Interactions

Rumora

Grubišić

2009

Archives of Industrial Hygiene and Toxicology

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A Journey Through Mitogen-Activated Protein Kinase and Ochratoxin A InteractionsOchratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, carcinogenic, and cytotoxic action. It has been proposed that OTA might be involved in the development of Balkan endemic nephropathy, which is associated with an increased risk of urinary tract tumours, and of other forms of interstitial nephritis. Cell susceptibility to OTA mainly depends on mycotoxin concentrations, duration of exposure, and intracellular molecular and genetic context. OTA can affect a cell by stimulating or inhibiting certain signalling pathways such as mitogen-activated protein kinase (MAPK). Three major mammalian MAPKs have been described: extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. All MAPKs regulate diverse cellular programmes, but in most cases ERKs have been linked to cell survival, while JNKs, and p38 MAPKs have been implicated in cell death by apoptosis. This review looks into OTA-mediated MAPK activation and its effects.

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Ochratoxin A at nanomolar concentrations: A signal modulator in renal cells

Cited by 89 publications

References 87 publications

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies

The occurrence of ochratoxin A in white and parboiled rice

A Journey Through Mitogen-Activated Protein Kinase and Ochratoxin A Interactions

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