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First determination of the highly genotoxic fungal contaminant altertoxin II in a naturally infested apple sample

Emerging Contaminants 2020年第1期6卷 82-86页

作者： Hannes Puntscher doris marko Benedikt Warth Department of Food Chemistry and Toxicology Faculty of ChemistryUniversity of ViennaWahringer Str.381090ViennaAustria

Altertoxin II is an epoxide-holding perylene quinone and secondary metabolite produced by Alternaria *** genotoxic potential and the high concentrations determined in laboratory fungal cultures resulted in an increased scientific interest in this emerging ***,no natural occurrence in food has been reported to date to the best of our ***,we unambiguously identified altertoxin II in a naturally infected,unprocessed *** a validated LC-MS/MS method,fruit peel spots(approx.1 mm in diameter),typically associated with Alternaria infestation,were tested for 17 mycotoxins produced by this *** concentrations of tentoxin were determined 24 h after harvest,and the dibenzopyrones alternariol,alternariol monomethyl ether(AME)and AME-3-sulfate after six months of ***,these contamination patterns can be considered unlikely to be of toxicological concern for ***,an inconspicuous peel lesion(0.5×1 cm)separately sampled from a stored apple,exhibited considerably high concentrations of 14 Alternaria toxins,including dibenzopyrones,their barely studied modified forms(glucosides and sulfates),as well as genotoxic perylene quinones including altertoxin *** the toxicological potential of this compound,contaminations in such infected fruit parts should not be underestimated,*** the case of exposure through the consumption of fresh smoothies or fruit juices.

关键词： Alternaria alternata Emerging contaminants Genotoxicity Food safety Plant pathology Liquid chromatography tandem mass spectrometry

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N-acetyl cysteine alters the genotoxic and estrogenic properties of Alternaria toxins in naturally occurring mixtures

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Emerging Contaminants 2022年第1期8卷 30-38页

作者： Georg Aichinger Dino Grgic Julia Beisl Francesco Crudo Benedikt Warth Elisabeth Varga doris marko Department of Food Chemistry and Toxicology University of ViennaAustria Department of Health Sciences and Technology ETH ZurichSwitzerland

It is unclear if complex mycotoxin mixtures produced by Alternaria *** estrogenic and/or genotoxic under physiological conditions,particularly considering the co-occurrence with antioxidants in ***,this study focused on enlightening the impact of N-acetyl cysteine(NAC),as a representative antioxidative SH-donor,on the mentioned toxicological endpoints of the signature Alternaria toxins alternariol(AOH),altertoxin-II(ATX-II)and a complex extract(CE)of an Alternaria alternata *** Ishikawa cells as an in vitro model,we monitored alterations in toxin concentrations by LC-MS/MS,estrogenicity by alkaline phosphatase assays,cytotoxicity by sulforhodamine B assays,genotoxicity by single-cell gel electrophoresis and the transcription of selected genes of interest by quantitative realtime *** results indicate that the strong genotoxic effects of epoxide-carrying perylene quinones such as ATX-II are erased in the presence of *** cellular effects of ATX-II/AOH mixtures are dominated by the genotoxicity of the perylene *** this mixture,AOH regained its estrogenicity when coincubated with *** contrast,NAC treatment of an AOH/CE mixture did not result in a recovery of estrogenicity,but in potentiated anti-estrogenic *** findings were in line with gene transcription data,that indicated the aryl hydrocarbon receptor(AhR)to be a prime mediator of Alternaria toxin e induced antagonistic effects towards estrogen receptor *** together,further studies on potential endocrine-disruptive properties of non-genotoxic perylene quinones should be a future research priority in the field of these emerging contaminants.

关键词： Mycotoxin DNA damage Xenoestrogen Combinatory toxicology Food contaminant Mixture effects

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Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2024年第13期30卷 1899-1910页

作者： Ante Tonkic marko Kumric Ivna Akrapovic Olic doris Rusic Piero Marin Zivkovic Daniela Supe Domic Zeljko Sundov Ivan Males Josko Bozic Biology of Neoplasms University of Split School of MedicineSplit 21000Croatia Department of Pathophysiology University of Split School of MedicineSplit 21000Croatia Department of Gastroenterology University Hospital of SplitSplit 21000Croatia Department of Pharmacy University of Split School of MedicineSplit 21000Croatia Department of Medical Laboratory Diagnostics University Hospital of SplitSplit 21000Croatia Department of Health Studies University of SplitSplit 21000Croatia Department of Internal Medicine University of Split School of MedicineSplit 21000Croatia Department of Surgery University Hospital of SplitSplit 21000Croatia

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and ***-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many *** To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple *** additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with *** This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched *** patients underwent an extensive workup,including colonoscopy with subsequent histopathological *** activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring ***-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence *** In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was ***,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to I

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Growth-differentiation factor-15 Anemia Extraintestinal manifestations

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Urotensin II levels in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2021年第36期27卷 6142-6153页

作者： Damir Alicic Dinko Martinovic doris Rusic Piero Marin Zivkovic Ivana Tadin Hadjina Marino Vilovic marko Kumric Daria Tokic Daniela Supe-Domic Slaven Lupi-Ferandin Josko Bozic Department of Gastroenterology University Hospital of SplitSplit 21000Croatia Department of Pathophysiology University of Split School of MedicineSplit 21000Croatia Department of Pharmacy University of Split School of MedicineSplit 21000Croatia Department of Anesthesiology and Intensive care University Hospital of SplitSplit 21000Croatia Department of Health Studies University of SplitSplit 21000Croatia Department of Maxillofacial Surgery University Hospital of SplitSplit 21000Croatia

BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular *** the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as ***,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy *** the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and *** To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical *** This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched *** assessment was performed by the same experienced gastroenterologist according to the latest *** Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic *** levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s *** IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII leve

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Urotensin II Cardiovascular risk Endoscopic activity

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