Citrinin-induced mitochondrial permeability transition

Lozzo, Eneida Janiscki Da; Oliveira, Maria Benigna Martinelli de; Carnieri, Eva Gunilla Skare

doi:10.1002/(sici)1099-0461(1998)12:5<291::aid-jbt5>3.0.co;2-g

Cited by 45 publications

(19 citation statements)

References 22 publications

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“…There are dozens of reports showing that high doses of citrinin act as a cytotoxin and nephrotoxin (Ambrose and DeEds, 1946;Friis et al, 1969;Krogh et al, 1970;Scott et al, 1972;Nelson et al, 1985;Aleo et al, 1991;Chagas et al, 1992aChagas et al, , 1992bDa Lozzo et al, 1998;Abramson et al, 2001;Liu et al, 2003;Yu et al, 2006;Bouslimi et al, 2008). In contrast, our results indicate a new role/implication for low-dose citrinin in health and disease.…”

Section: Discussionmentioning

confidence: 41%

“…The toxicities of citrinin have been frequently reported as cytotoxic (50-220 μM, 24-72 hr as LC 50 , which depends on cell type) (Liu et al, 2003;Yu et al, 2006;Bouslimi et al, 2008) and nephrotoxic via swelling of the kidney and acute tubular necrosis (50-134 mg/kg orally as LD 50 , which depends on species) (Ambrose and DeEds, 1946;Friis et al, 1969;Krogh et al, 1970). The mechanism of citrinin toxicity is thought to involve mitochondrial dysfunction (Aleo et al, 1991;Chagas et al, 1992aChagas et al, , 1992bDa Lozzo et al, 1998). Furthermore, citrinin affects intracellular calcium level (Berndt et al, 1984;Chan, 2008;Klarić et al, 2012) so that citrinin has the potential to influence the cellular events regulated by calcium influx.…”

Section: Introductionmentioning

confidence: 99%

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Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

et al. 2016

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-Citrinin, a natural mycotoxin that is found in fermented foods, is known as a cytotoxin and nephrotoxin. Exposure to high doses of citrinin result in apoptosis; however, the effects of low doses are not fully understood. Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and other neurodegenerative diseases. Here, we show the neuroprotective effect of low doses of citrinin against glutamate-induced excitotoxicity. We examined the effect of citrinin exposure on glutamate-induced cell death in cultured rat cortical neurons under two conditions: simultaneous treatment with citrinin 0.1 to 1,000 nM and glutamate (30 μM) for 1, 3 hr; the same simultaneous treatment for 3 hr after pretreatment with citrinin for 21 hr. Both the MTT and immunocytochemical assay showed significant neuroprotective effects at several doses and exposure times tested. All concentrations of citrinin tested showed no remarkable cell death following 14-day exposure, and no marked alterations to synapses. These data suggest that low doses of citrinin can be used as a neuroprotective agent against glutamate-induced excitotoxicity without additional harmful cellular alterations.

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Section: Discussionmentioning

confidence: 41%

Section: Introductionmentioning

confidence: 99%

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

et al. 2016

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“…In rat liver catalase, butylhydroxitoluene, and dithiothreitol did not protect against swelling and against increased mitochondrial permeability caused by Ca 2+ plus citrinin (48). Protection conferred by ATP-Mg 2+ and cyclosporine A indicates pore formation.…”

Section: Effects On Renal Function and Structurementioning

confidence: 80%

Toxicological Properties of Citrinin

Flajs

Peraica

2009

Archives of Industrial Hygiene and Toxicology

174

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Citrinin (CTN) is a nephrotoxic mycotoxin produced by several fungal strains belonging to the genera Penicillium, Aspergillus, and Monascus. It contaminates various commodities of plant origin, cereals in particular, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A (OTA). These two mycotoxins are believed to be involved in the aetiology of endemic nephropathy. In addition to nephrotoxicity, CTN is also embryocidal and fetotoxic. The genotoxic properties of CTN have been demonstrated with the micronuleus test (MN), but not with single-cell gel electrophoresis. The mechanism of CTN toxicity is not fully understood, especially not whether CTN toxicity and genotoxicity are the consequence of oxidative stress or of increased permeability of mitochondrial membranes. CTN requires complex cellular biotransformation to exert mutagenicity. Compared with other mycotoxins, CTN contamination of food and feed is rather scarce. However, it is reasonable to believe that humans are much more frequently exposed to CTN than generally accepted, because it is produced by the same moulds as OTA, which is a common contaminant of human food all over the world. At present, there are no specifi c regulations either in Croatia or in the European Union concerning CTN in any kind of commodity.

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“…Since in mammalian cells the homologous organelle for the yeast vacuole is the lysosome (Pevsner et al 1996) it will be important to determine the in¯uence of lysosomal functions on the toxicity of citrinin (DaLozzo et al 1998;Dirheimer 1998), especially in renal cells (Galtier 1998).…”

Section: Discussionmentioning

confidence: 99%

A screen of yeast respiratory mutants for sensitivity against the mycotoxin citrinin identifies the vacuolar ATPase as an essential factor for the toxicity mechanism

2000

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In countries with a hot climate the mycotoxin citrinin represents a serious problem in fungal food-poisoning. In humans the renal system is affected the most and the mitochondrial respiratory chain was identified as a possible sensitive target for this toxin. In addition, citrinin has an antifungal activity that also inhibits the growth of the yeast Saccharomyces cerevisiae. So far the precise mode of action and the subcellular targets for citrinin have not been identified. Therefore, we decided to use the model organism yeast for a genetic approach to identify genes that play a role in the sensitivity against this mycotoxin. A large collection of conditional respiratory deficient yeast mutants was screened for sensitivity against citrinin. One special pet-ts mutant was identified that exhibited a higher sensitivity against citrinin. The genetic system of yeast allowed the isolation of the respective wild-type gene. This yeast gene encodes the Vph2p subunit that is essential for the correct assembly of the vacuolar ATPase. Isolation of the mutated gene and gene-disruption experiments of VPH2 and the partially overlapping small YKL118W gene verified this finding. The wild-type VPH2 gene restores all defects of the mutants. In contrast to this, YKL118W gave no complementation and the null mutant showed no phenotype. Thereby the yeast vacuolar ATPase was found to be important for the toxic effect of citrinin in yeast cells. The consequences of this finding for the molecular mechanism of citrinin action and its relation to the mitochondrial respiratory chain are discussed.

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Citrinin-induced mitochondrial permeability transition

Cited by 45 publications

References 22 publications

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

Toxicological Properties of Citrinin

A screen of yeast respiratory mutants for sensitivity against the mycotoxin citrinin identifies the vacuolar ATPase as an essential factor for the toxicity mechanism

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