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Maja Šegvić Klarić, PhD is Full Professor at the Department of Microbiology. She is a Head of Department from 2018. She teaches Microbiology and Parasitology (co-lecturer), Applied Microbiology (lecturer), Diagnostics and Therapy of Viral Infections (co-lecturer) and Basics of Epidemiology with Microbiological Diagnostics (associate lecturer). She teaches courses at postgraduate doctoral level Mycotoxicology (lecturer) and Pharmaceutical Microbiology with Mycotoxicology (associate lecturer) at Faculty of Pharmacy and Biochemistry. At Postgraduate specialist study of Toxicology she teaches Mycotoxicology and Mycology Basics (lecturer). The area of her scientific research interest includes mycotoxins, mechanisms of their toxicity and interactions in vitro as well as testing of the antimicrobial activity of different substances and therapeutic systems on Staphylococcus aureus biofilm.
Project Goal: Aspergilli in floded and control vilage houses in Croatia; Aspergilli production of mycotoxins in vitro; fungal metabolites in hous dust and foods; toxicity in vitro and in vivo of the most frequent mycotoxins found in dust,
Current Stage: Finished 07/12/2020
Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are structurally related mycotoxins with cytotoxic and genotoxic properties. In the present study, we hypothesized that DNA damage induced by non-cytotoxic concentrations of single and combined mycotoxins could alter the phosphorylation of the checkpoint proteins Chk2 and FANCD2 (ELISA) in HepG2 and A549 cells. The cytotoxic potential (MTT test) of single and combined STC and 5-M-STC, the nature of their interaction (additivity, antagonism, or synergy) and DNA damage level (alkaline comet assay) in HepG2 and A549 cells were also investigated. All experiments were performed after 24 h of mycotoxin treatment. 5-M-STC was 10-folds more cytotoxic than STC to both HepG2 and A549 cells. Both mycotoxins are genotoxic to HepG2 and A549 cells by inducing both double and single DNA strand breaks that activate Chk2 (especially in HepG2 cells) but not the FANCD2 protein. STC exerted higher genotoxic potential than 5-M-STC in HepG2 and A549 cells when both toxins were applied individually at the same concentration. Dual combinations of non-cytotoxic mycotoxin concentrations showed additive to antagonizing cytotoxic and genotoxic effects. The absence and low activation of checkpoint proteins during prolonged exposure to non-cytotoxic concentrations of STC and 5-M-STC could support cell proliferation and carcinogenesis.
Sanja Dabelić; Domagoj Kifer; Daniela Jakšić; Nevenka Kopjar; Maja Klarić. Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins. Toxins 2021, 13, 464 .
AMA StyleSanja Dabelić, Domagoj Kifer, Daniela Jakšić, Nevenka Kopjar, Maja Klarić. Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins. Toxins. 2021; 13 (7):464.
Chicago/Turabian StyleSanja Dabelić; Domagoj Kifer; Daniela Jakšić; Nevenka Kopjar; Maja Klarić. 2021. "Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins." Toxins 13, no. 7: 464.
A total of 117 fungal metabolites were detected in grains collected in Gunja-G (flooded village) and Gornji Stupnik-GS (control village), located in the Zagreb County, Croatia. Major mycotoxins and derivatives (17), ergot alkaloids (14), Fusarium (23), Aspergillus (18), Penicillium (18), Alternaria (7) and other fungal and unspecific metabolites (20) were found. A higher number of metabolites co-occurred per sample in grains from G (115) than in GS (91). Regulated mycotoxins were below maximum limits except fumonisins B1,2 in 15–20% of grains and aflatoxin B1. Fusarium metabolites contaminated more than 50% of grains at both locations. Besides FB1,2, bikaverin, aurofusarin, culmorin and 15-hidroxyculmorin were detected at relatively high concentrations. Ergot alkaloids were detected at 2–18 times higher concentrations in grains from G as compared to GS. Majority of Aspergillus mycotoxins were present at a low frequency (5–15%). Penicillium metabolites recovered with higher frequency in GS (55–70%) than in G (20–55%). Alteranaria metabolites prevailed in grains from G (60–80%).
Domagoj Kifer; Michael Sulyok; Daniela Jakšić; Rudolf Krska; Maja Šegvić Klarić. Fungi and their metabolites in grain from individual households in Croatia. Food Additives and Contaminants: Part B 2021, 14, 98 -109.
AMA StyleDomagoj Kifer, Michael Sulyok, Daniela Jakšić, Rudolf Krska, Maja Šegvić Klarić. Fungi and their metabolites in grain from individual households in Croatia. Food Additives and Contaminants: Part B. 2021; 14 (2):98-109.
Chicago/Turabian StyleDomagoj Kifer; Michael Sulyok; Daniela Jakšić; Rudolf Krska; Maja Šegvić Klarić. 2021. "Fungi and their metabolites in grain from individual households in Croatia." Food Additives and Contaminants: Part B 14, no. 2: 98-109.
In winter and summer of 2016 and 2017, airborne fungi and house dust were collected in indoors of the village Gunja, which had been flooded, and the control village Gornji Stupnik (Croatia) in order to explore variations of fungal indoor levels, particularly Aspergilli section Nidulantes series Versicolores, as well as fungal metabolites in dust. Levels of airborne Aspergilli (Versicolores) were three times as high in winter and summer in Gunja than in the control village, while dustborne isolates were equally present in both locations. Sequencing of the calmodulin gene region revealed that among Aspergilli (Versicolores), A. jensenii and A. creber were dominant and together with A. puulaauensis, A. tennesseensis and A. venenatus produced sterigmatocystin and 5‐methoxysterigmatocystin (HPLC coupled with mass spectrometry); A. amoenus, A. fructus, A. griseoaurantiacus, A. pepii, and A. protuberus produced sterigmatocystin but not 5‐methoxysterigmatocystin; A. sydowii did not produce any of these toxins. A total of 75 metabolites related to Penicillium (29), Aspergillus (22), Fusarium (10), Alternaria (5), Stachybotrys (2), and other fungi (7) were detected in dust by liquid chromatography‐tandem mass spectrometry. The majority of metabolites including sterigmatocystin and 5‐methoxysterigmatocystin exhibited a higher prevalence in winter in Gunja.
Daniela Jakšić; Miranda Sertić; Domagoj Kifer; Sandor Kocsubè; Ana Mornar Turk; Biljana Nigović; Bojan Šarkanj; Rudolf Krska; Michael Sulyok; Maja Šegvić Klarić. Fungi and their secondary metabolites in water‐damaged indoors after a major flood event in eastern Croatia. Indoor Air 2020, 31, 730 -744.
AMA StyleDaniela Jakšić, Miranda Sertić, Domagoj Kifer, Sandor Kocsubè, Ana Mornar Turk, Biljana Nigović, Bojan Šarkanj, Rudolf Krska, Michael Sulyok, Maja Šegvić Klarić. Fungi and their secondary metabolites in water‐damaged indoors after a major flood event in eastern Croatia. Indoor Air. 2020; 31 (3):730-744.
Chicago/Turabian StyleDaniela Jakšić; Miranda Sertić; Domagoj Kifer; Sandor Kocsubè; Ana Mornar Turk; Biljana Nigović; Bojan Šarkanj; Rudolf Krska; Michael Sulyok; Maja Šegvić Klarić. 2020. "Fungi and their secondary metabolites in water‐damaged indoors after a major flood event in eastern Croatia." Indoor Air 31, no. 3: 730-744.
The original version of this article unfortunately contained a mistake. The author's first and last names were interchanged in the published version of this article. The corrected author names are given in this article.
Dubravka Rašić; Daniela Jakšić; Andrea Hulina Tomašković; Domagoj Kifer; Nevenka Kopjar; Lada Rumora; Davor Želježić; Maja Peraica; Maja Šegvić Klarić. Correction to: Sterigmatocystin moderately induces oxidative stress in male Wistar rats after short-term oral treatment. Mycotoxin Research 2020, 37, 117 -117.
AMA StyleDubravka Rašić, Daniela Jakšić, Andrea Hulina Tomašković, Domagoj Kifer, Nevenka Kopjar, Lada Rumora, Davor Želježić, Maja Peraica, Maja Šegvić Klarić. Correction to: Sterigmatocystin moderately induces oxidative stress in male Wistar rats after short-term oral treatment. Mycotoxin Research. 2020; 37 (1):117-117.
Chicago/Turabian StyleDubravka Rašić; Daniela Jakšić; Andrea Hulina Tomašković; Domagoj Kifer; Nevenka Kopjar; Lada Rumora; Davor Želježić; Maja Peraica; Maja Šegvić Klarić. 2020. "Correction to: Sterigmatocystin moderately induces oxidative stress in male Wistar rats after short-term oral treatment." Mycotoxin Research 37, no. 1: 117-117.
Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series Versicolores. Since both STC and 5-M-STC were found in the dust of indoor occupational and living areas, their occupants may be exposed to these mycotoxins, primarily by inhalation. Thus, STC and 5-M-STC were intratracheally instilled in male Wistar rats using doses (0.3 mg STC/kg of lung weight (l.w.); 3.6 mg 5-M-STC/kg l.w.; toxin combination 0.3 + 3.6 mg/kg l.w.) that corresponded to concentrations detected in the dust of damp indoor areas in order to explore cytotoxicity, vascular permeability, immunomodulation and genotoxicity. Single mycotoxins and their combinations insignificantly altered lactate-dehydrogenase activity, albumin, interleukin-6, tumor necrosis factor-α and chemokine macrophage inflammatory protein-1α concentrations, as measured by ELISA in bronchioalveolar lavage fluid upon 24 h of treatment. In an alkaline comet assay, both mycotoxins provoked a similar intensity of DNA damage in rat lungs, while in a neutral comet assay, only 5-M-STC evoked significant DNA damage. Hence, naturally occurring concentrations of individual STC may induce DNA damage in rat lungs, in which single DNA strand breaks prevail, while 5-M-STC was more responsible for double-strand breaks. In both versions of the comet assay treatment with STC + 5-M-STC, less DNA damage intensity occurred compared to single mycotoxin treatment, suggesting an antagonistic genotoxic action.
Daniela Jakšić; Ida Ćurtović; Domagoj Kifer; Dubravka Rašić; Nevenka Kopjar; Vedran Micek; Maja Peraica; Maja Šegvić Klarić. Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs. Toxins 2020, 12, 734 .
AMA StyleDaniela Jakšić, Ida Ćurtović, Domagoj Kifer, Dubravka Rašić, Nevenka Kopjar, Vedran Micek, Maja Peraica, Maja Šegvić Klarić. Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs. Toxins. 2020; 12 (11):734.
Chicago/Turabian StyleDaniela Jakšić; Ida Ćurtović; Domagoj Kifer; Dubravka Rašić; Nevenka Kopjar; Vedran Micek; Maja Peraica; Maja Šegvić Klarić. 2020. "Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs." Toxins 12, no. 11: 734.
Mycotoxin-producing Aspergilli (Circumdati, Flavi, and Nigri), usually associated with contaminated food, may also cause respiratory disorders and are insufficiently studied in water-damaged indoor environments. Airborne (N = 71) and dust borne (N = 76) Aspergilli collected at post-flood and control locations in Croatia resulted in eleven different species based on their calmodulin marker: A. ochraceus, A. ostianus, A. pallidofulvus, A. sclerotiorum, and A. westerdijkiae (Circumdati); A. flavus (Flavi); and A. tubingensis, A. welwitschiae, A. niger, A. piperis, and A. uvarum (Nigri). Most of the airborne (73%) and dust borne (54%) isolates were found at post-flood locations, and the highest concentrations measured in indoor air (5720 colony-forming units (CFU)/m3) and dust (2.5 × 105 CFU/g) were up to twenty times higher than in the control locations. A. flavus dominated among airborne isolates (25%) at the unrepaired locations, while 56% of the dust borne Aspergilli were identified as A. tubingensis and A. welwitschiae. The ability of identified isolates to produce mycotoxins aflatoxin B1 (AFB1), fumonisin B2 (FB2), and ochratoxin A were assessed by LC-MS analysis. All ochratoxin A (OTA)-producing Circumdati belonged to A. westerdijkiae (13.7 ± 15.81 µg/mL); in the section, FlaviA. flavus produced AFB1 (2.51 ± 5.31 µg/mL), while A. welwitschiae and A. niger (section Nigri) produced FB2 (6.76 ± 13.51 µg/mL and 11.24 ± 18.30 µg/mL, respectively). Water damage dominantly supported the occurrence of aflatoxigenic A. flavus in indoor environments. Yet unresolved, the causal relationship of exposure to indoor Aspergilli and adverse health effects may support the significance of this research.
Daniela Jakšić; Miranda Sertić; Sándor Kocsubé; Ivana Kovačević; Domagoj Kifer; Ana Mornar; Biljana Nigović; Maja Šegvić Klarić. Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment. Journal of Fungi 2020, 6, 282 .
AMA StyleDaniela Jakšić, Miranda Sertić, Sándor Kocsubé, Ivana Kovačević, Domagoj Kifer, Ana Mornar, Biljana Nigović, Maja Šegvić Klarić. Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment. Journal of Fungi. 2020; 6 (4):282.
Chicago/Turabian StyleDaniela Jakšić; Miranda Sertić; Sándor Kocsubé; Ivana Kovačević; Domagoj Kifer; Ana Mornar; Biljana Nigović; Maja Šegvić Klarić. 2020. "Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment." Journal of Fungi 6, no. 4: 282.
Crops contaminated by aflatoxins (AFs), the toxic and carcinogenic mycotoxins produced namely by Aspergillus flavus and Aspergillus parasiticus, have severe impacts on human health. Changes in temperature and water availability related to actual climate changes (increased temperature, heavy rainfalls, and droughts) are modulating factors of mould growth and production of mycotoxins. To protect human and animal health from the harmful effects caused by AFs, the development of a safe and effective multifaceted approach in combating food and feed contamination with AFs is necessary. This review aims to collect and analyze the available information regarding AF presence in food and feed to reinforce AF management and to prevent health issues related to the AF exposure in the light of actual climate changes.
Rafael Valencia-Quintana; Mirta Milić; Daniela Jakšić; Maja Šegvić Klarić; María Tenorio-Arvide; Guillermo Pérez-Flores; Stefano Bonassi; Juana Sánchez-Alarcón. Environment Changes, Aflatoxins, and Health Issues, a Review. International Journal of Environmental Research and Public Health 2020, 17, 7850 .
AMA StyleRafael Valencia-Quintana, Mirta Milić, Daniela Jakšić, Maja Šegvić Klarić, María Tenorio-Arvide, Guillermo Pérez-Flores, Stefano Bonassi, Juana Sánchez-Alarcón. Environment Changes, Aflatoxins, and Health Issues, a Review. International Journal of Environmental Research and Public Health. 2020; 17 (21):7850.
Chicago/Turabian StyleRafael Valencia-Quintana; Mirta Milić; Daniela Jakšić; Maja Šegvić Klarić; María Tenorio-Arvide; Guillermo Pérez-Flores; Stefano Bonassi; Juana Sánchez-Alarcón. 2020. "Environment Changes, Aflatoxins, and Health Issues, a Review." International Journal of Environmental Research and Public Health 17, no. 21: 7850.
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.
Domagoj Kifer; Daniela Jakšić; Maja Šegvić Klarić. Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate? Toxins 2020, 12, 153 .
AMA StyleDomagoj Kifer, Daniela Jakšić, Maja Šegvić Klarić. Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate? Toxins. 2020; 12 (3):153.
Chicago/Turabian StyleDomagoj Kifer; Daniela Jakšić; Maja Šegvić Klarić. 2020. "Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?" Toxins 12, no. 3: 153.
This study aimed to explore involvement of oxidative stress in sterigmatocystin (STC) toxicity in male Wistar rats. Animals were orally treated with a single STC dose (10, 20 and 40 mg/kg b.w.). Short-term treatment resulted in moderate oxidative stress determined by a significant increase of malondialdehyde (MDA; all STC doses) and catalase (CAT; 10 mg/kg b.w.) in plasma, a decrease of glutathione peroxidase (GPx; 20 and 40 mg/kg b.w.) in the liver, and increase of MDA and superoxide dismutase (SOD) in kidneys (all STC doses). Heat shock protein (Hsp27 and Hsp70) expression was determined by Western blotting in rat liver and kidneys. Hsp27 expression was downregulated by STC, particularly in the liver (40 mg/kg b.w.). The lowest STC dose elevated the expression of Hsp70 in both liver and kidneys, while an increase in STC doses restored Hsp70 expression to control. Alterations in expressions of Hsp27 and Hsp70 could be only partially associated with oxidative stress. STC provoked a significant DNA damage in both liver and kidneys (alkaline comet assay), but the liver was more affected by a broader spectrum of DNA lesions. Oxidative DNA damage (hOGG1-modified comet assay) contribute to the overall mechanism of STC-induced DNA damage in both organs, but kidneys in general seem to be more susceptible to oxidative stress upon short-term exposure to sublethal doses of STC.
Rašić Dubravka; Jakšić Daniela; Hulina Tomašković Andrea; Kifer Domagoj; Kopjar Nevenka; Rumora Lada; Želježić Davor; Peraica Maja; Šegvić Klarić Maja. Sterigmatocystin moderately induces oxidative stress in male Wistar rats after short-term oral treatment. Mycotoxin Research 2019, 36, 181 -191.
AMA StyleRašić Dubravka, Jakšić Daniela, Hulina Tomašković Andrea, Kifer Domagoj, Kopjar Nevenka, Rumora Lada, Želježić Davor, Peraica Maja, Šegvić Klarić Maja. Sterigmatocystin moderately induces oxidative stress in male Wistar rats after short-term oral treatment. Mycotoxin Research. 2019; 36 (2):181-191.
Chicago/Turabian StyleRašić Dubravka; Jakšić Daniela; Hulina Tomašković Andrea; Kifer Domagoj; Kopjar Nevenka; Rumora Lada; Želježić Davor; Peraica Maja; Šegvić Klarić Maja. 2019. "Sterigmatocystin moderately induces oxidative stress in male Wistar rats after short-term oral treatment." Mycotoxin Research 36, no. 2: 181-191.
We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300–400 nm range. Results showed that these CD bands do not originate from intrinsic STC chirality but are a specific property of a peculiar aggregation process similar to psi-DNA CD response. Transmission electron microscopy (TEM) experiments revealed a fine fiber network resembling a supramolecular gel structure with helical fibers. Thermodynamic studies of aggregates by differential scanning calorimetry (DSC) revealed high reversibility of the dominant aggregation process. We demonstrated that the novel STC psi-CD band at 345 nm could be applied at biorelevant conditions (100 nanomolar concentration) and even in marine-salt content conditions for specific and quantitative monitoring of STC. Also, we showed that STC strongly non-covalently interacts with ds-DNA with likely toxic effects, thus contrary to the previous belief requiring prior enzyme epoxidation.
Daniela Jakšić; Maja Šegvić Klarić; Ivo Crnolatac; Nataša Šijaković Vujičić; Vilko Smrečki; Marcin Górecki; Gennaro Pescitelli; Ivo Piantanida. Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions. Marine Drugs 2019, 17, 629 .
AMA StyleDaniela Jakšić, Maja Šegvić Klarić, Ivo Crnolatac, Nataša Šijaković Vujičić, Vilko Smrečki, Marcin Górecki, Gennaro Pescitelli, Ivo Piantanida. Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions. Marine Drugs. 2019; 17 (11):629.
Chicago/Turabian StyleDaniela Jakšić; Maja Šegvić Klarić; Ivo Crnolatac; Nataša Šijaković Vujičić; Vilko Smrečki; Marcin Górecki; Gennaro Pescitelli; Ivo Piantanida. 2019. "Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions." Marine Drugs 17, no. 11: 629.
Aspergilli section Versicolores are among the most frequent primary fungal colonizers of damp indoors, known to produce mycotoxin sterigmatocystin (STC). These Aspergilli dominated among Aspergillus species isolated from air and dust sampled in flood affected homes (Gunja, Croatia) and control houses (Gornji Stupnik, Croatia). In the present study we investigated: a) biodiversity of the Aspergillus section Versicolores isolates based on partial calmodulin sequences and b) pro-inflammatory effects (ELISA) of STC vs STC-producing Aspergilli using THP-1 macrophage-like cells. Most of the Versicolores isolates were from the flood affected area (91/125). A. jensenii and A. creber were the most frequent species (31 % and 30 %, respectively) followed by A. puulaauensis (10 %), A. protuberus (9 %), A. tennesseensis (6 %), A. sydowii (5 %), A. amoenus (3 %), A. venenatus (2 %), A. fructus (1.6 %), A. griseoaurantiacus (1 %) and A. pepii (1 %). As A. creber was among the most frequent species it was chosen for experiments on THP-1 cells. Subcytotoxic concentrations of STC (0.1 and 1 µM) and A. creber extract containing the same concentrations of STC showed different inflammatory effect in THP-1 cells; STC induced significant concentration-dependent increase of IL-1β, IL-6 and IL-8 and decrease of TNF-α, while A. creber did not significantly affect cytokine levels compared to control (0.1% DMSO). Differences in inflammatory effects of single STC and A. creber may be explained by the presence of other metabolites in the extract which might have antagonised STC. This work has been fully supported by Croatian Science Foundation under the project MycotoxA (IP-09-2014-5982).
Maja Šegvić Klarić; Daniela Jakšić; Sándor Kocsubé. Biodiversity and inflammatory properties of Aspergillus section Versicolores - what flood has to do with it? Occupational and environmental health 2019, 54, 1 .
AMA StyleMaja Šegvić Klarić, Daniela Jakšić, Sándor Kocsubé. Biodiversity and inflammatory properties of Aspergillus section Versicolores - what flood has to do with it? Occupational and environmental health. 2019; 54 ():1.
Chicago/Turabian StyleMaja Šegvić Klarić; Daniela Jakšić; Sándor Kocsubé. 2019. "Biodiversity and inflammatory properties of Aspergillus section Versicolores - what flood has to do with it?" Occupational and environmental health 54, no. : 1.
The study aimed to check whether ochratoxin A (OTA) and citrinin (CIT) increase DNA damage in the kidney and liver of male Wistar rats (alkaline comet assay), clarify the oxidative nature of DNA damage (hOGG1-modified comet assay), and verify whether resveratrol (RSV) could ameliorate OTA+CIT-induced genotoxicity. Rats were treated orally with OTA (0.125 and 0.250 mg/kg bodyweight (bw)) and CIT (2 mg/kg bw), OTA+CIT combinations and OTA+CIT+RSV (0.250+2+20 mg/kg bw) for 21 days. Both alkaline and hOGG1-modified comet assay showed that DNA damage was more severe in rat kidneys than in liver following mycotoxin treatment. Alkaline comet assay revealed a higher intensity of DNA damage, particularly as measured by tail intensity in the kidneys. Both tail length and tail intensity were OTA dose-dependent, but in combined OTA+CIT treatment these values were similar to CIT alone and lower than in animals treated with single OTA, possibly due to induction of apoptosis. hOGG1-modified comet showed that OTA+CIT evoked greater oxidative DNA damage than single mycotoxins. RSV did not reduce DNA damage measured by alkaline comet assay, but hOGG1-modified comet showed that RSV ameliorated OTA+CIT genotoxicity in the kidneys. Apart from oxidative stress, other mechanisms of DNA damage are involved in OTA and CIT genotoxicity. In rat kidneys RSV can reduce but not overcome oxidative DNA damage induced by combined OTA and CIT.
D. Rašić; D. Želježić; N. Kopjar; Domagoj Kifer; M. Šegvić Klarić; M. Peraica. DNA damage in rat kidneys and liver upon subchronic exposure to single and combined ochratoxin A and citrinin. World Mycotoxin Journal 2019, 12, 163 -172.
AMA StyleD. Rašić, D. Želježić, N. Kopjar, Domagoj Kifer, M. Šegvić Klarić, M. Peraica. DNA damage in rat kidneys and liver upon subchronic exposure to single and combined ochratoxin A and citrinin. World Mycotoxin Journal. 2019; 12 (2):163-172.
Chicago/Turabian StyleD. Rašić; D. Želježić; N. Kopjar; Domagoj Kifer; M. Šegvić Klarić; M. Peraica. 2019. "DNA damage in rat kidneys and liver upon subchronic exposure to single and combined ochratoxin A and citrinin." World Mycotoxin Journal 12, no. 2: 163-172.
Aspergilli section Flavi, originally isolated from air samples collected from inhabited apartments (AP), unoccupied basements (BS), and processing facilities of a grain mill (GM), were analyzed for their potential to produce aflatoxin B1 (AFB1) on solid media. The isolates were further characterized with regard to their cytotoxic, genotoxic, and pro-inflammatory properties in vitro. Aspergilli were identified based on partial calmodulin (CaM) gene sequencing; the producing capacities of isolates were analyzed by HPLC/FLD and confirmed by genes in biosynthesis (aflR, norA, omtA). In the grain mill, the Aspergilli section Flavi (up to 1.3 × 106 cfu/m3) dominated by AFB1-producing Aspergillus flavus (71%, 4.5–5254 ng/ml) which showed a serious health risk for workers. Living environments were not relevant sources of exposure. After 24 h, AFB1 (1–100 μmol/l) reduced cell viability (MTT test) in both A549 cells and THP-1 macrophage-like cells without reaching IC50. In A549 cells, the extract of the AFB1-producing A. flavus significantly decreased cell viability but not below 50%. THP-1 macrophage-like cells were more sensitive to both extracts, but IC50 was obtained only for the AFB1-producing strain (0.37 mg/ml; AFB1 2.78 μmol/l). AFB1 (1 and 10 μmol/l) induced significant DNA damage (tail intensity, alkaline comet assay) in A549 cells in contrast to Aspergilli extracts. AFB1 elevated IL-6 and IL-8, while Aspergilli extracts increased IL-1β, TNF-α, and IL-17 release in THP-1 macrophages (ELISA). Chronic exposure to AFB1 and/or other metabolites in airborne A. flavus from occupational environments may stimulate epithelial damage of airways accompanied by lowered macrophage viability.
Daniela Jakšić; Sándor Kocsubé; Ottó Bencsik; Anita Kecskeméti; András Szekeres; Dubravko Jelić; Nevenka Kopjar; Csaba Vágvölgyi; János Varga; Maja Šegvić Klarić. Aflatoxin production and in vitro toxicity of Aspergilli section Flavi isolated from air samples collected from different environments. Mycotoxin Research 2019, 35, 217 -230.
AMA StyleDaniela Jakšić, Sándor Kocsubé, Ottó Bencsik, Anita Kecskeméti, András Szekeres, Dubravko Jelić, Nevenka Kopjar, Csaba Vágvölgyi, János Varga, Maja Šegvić Klarić. Aflatoxin production and in vitro toxicity of Aspergilli section Flavi isolated from air samples collected from different environments. Mycotoxin Research. 2019; 35 (3):217-230.
Chicago/Turabian StyleDaniela Jakšić; Sándor Kocsubé; Ottó Bencsik; Anita Kecskeméti; András Szekeres; Dubravko Jelić; Nevenka Kopjar; Csaba Vágvölgyi; János Varga; Maja Šegvić Klarić. 2019. "Aflatoxin production and in vitro toxicity of Aspergilli section Flavi isolated from air samples collected from different environments." Mycotoxin Research 35, no. 3: 217-230.
Antibiotic delivery via liposomal encapsulation represents a promising approach for the efficient topical treatment of skin infections. The present study aimed to investigate the potential of using different types of azithromycin (AZT)-loaded liposomes to locally treat skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains. Conventional liposomes (CLs), deformable liposomes (DLs), propylene glycol-containing liposomes (PGLs) and cationic liposomes (CATLs) encapsulating AZT were prepared, and their physical characteristics, drug release profiles, ex vivo skin penetration/deposition abilities, in vitro anti-MRSA activities (planktonic bacteria and biofilm) and cell biocompatibilities were assessed. The (phospho)lipid composition and presence of surfactant or propylene glycol affected the physical characteristics of the liposomes, the release profile of AZT, its deposition inside the skin, as well as in vitro antibacterial efficacy and tolerability with the skin cells. All the liposomes retained AZT inside the skin more efficiently than did the control and were biocompatible with keratinocytes and fibroblasts. CATLs, DLs and PGLs efficiently inhibited MRSA strain growth and were superior to free AZT in preventing biofilm formation, exhibiting minimal inhibitory concentrations and minimal biofilm inhibitory concentrations up to 32-fold lower than those of AZT solution, thus confirming their potential for improved topical treatment of MRSA-caused skin infections.
Zora Rukavina; Maja Šegvić Klarić; Jelena Filipović-Grčić; Jasmina Lovrić; Željka Vanić. Azithromycin-loaded liposomes for enhanced topical treatment of methicillin-resistant Staphyloccocus aureus (MRSA) infections. International Journal of Pharmaceutics 2018, 553, 109 -119.
AMA StyleZora Rukavina, Maja Šegvić Klarić, Jelena Filipović-Grčić, Jasmina Lovrić, Željka Vanić. Azithromycin-loaded liposomes for enhanced topical treatment of methicillin-resistant Staphyloccocus aureus (MRSA) infections. International Journal of Pharmaceutics. 2018; 553 (1-2):109-119.
Chicago/Turabian StyleZora Rukavina; Maja Šegvić Klarić; Jelena Filipović-Grčić; Jasmina Lovrić; Željka Vanić. 2018. "Azithromycin-loaded liposomes for enhanced topical treatment of methicillin-resistant Staphyloccocus aureus (MRSA) infections." International Journal of Pharmaceutics 553, no. 1-2: 109-119.
Species assigned to Aspergillus section Flavi are food contaminants and may cause mycoses. Higher humidity may favour their occurrence in indoor environments and support the biosynthesis of aflatoxin B1 (AFB1), their toxic and cancerogenic metabolite. The aim of this study was to compare the frequencies of aflatoxin-producing and non-producing Aspergilli isolated from flood affected and control area in Croatia. Additionally, comet assay was employed to evaluate their genotoxic potential. Aspergilli of interest were isolated from air (N=60) and dust (N=60) samples collected during 2016 and 2017, two and three years after flood in Eastern Croatia. Identification of the isolates was based on morphology and the partial calmodulin sequences. Microextracts prepared from fungal cultures were analysed on AFB1 content by LC/MS. Genotoxicity of extracted Aspergilli was tested in human lung adenocarcinoma cell line A549 by alkaline comet-assay. Aspergilli (Flavi) dominated in the samples collected in flood-affected area (33/40) compared to the control area (3/40) and were more frequent in the airsamples (83%). AFB1 producing abilities were confirmed only for isolates from flood affected area (10/33). Genotoxic potential measured as tail intensity (% of DNA in comet tail) was slightly higher for AFB1-negative compared to AFB1-positive extract (0.57 ±0.94 and 0.14 ± 0.31, respectively). Flood may support the occurrence of Aspergilli from section Flavi in indoor environments. Inhalation of these mycoparticles may have a harmful effect on the respiratory system of the exposed people regardless of AFB1 presence. This work has been fully supported by Croatian Science Foundation under the project MycotoxA (IP-09-2014-5982).
Daniela Jakšić; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Nevenka Kopjar; Biljana Nigović; Maja Šegvić Klarić. Post-flood risks of inhalatory exposure to Aspergillus section Flavi. Occupational and Environmental Health 2018, 52, PA1196 .
AMA StyleDaniela Jakšić, Miranda Sertić, Ana Mornar Turk, Domagoj Kifer, Nevenka Kopjar, Biljana Nigović, Maja Šegvić Klarić. Post-flood risks of inhalatory exposure to Aspergillus section Flavi. Occupational and Environmental Health. 2018; 52 ():PA1196.
Chicago/Turabian StyleDaniela Jakšić; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Nevenka Kopjar; Biljana Nigović; Maja Šegvić Klarić. 2018. "Post-flood risks of inhalatory exposure to Aspergillus section Flavi." Occupational and Environmental Health 52, no. : PA1196.
This study presents the distribution of fumonisin (FB)-producing and non-producing airborne Aspergilli (Nigri) in apartments (AP), basements (BS) and a grain mill (GM) in Croatia, and their cytotoxic, immunomodulation and genotoxic potency in comparison with FB1 and FB2. Concentration of black Aspergilli was 260-fold higher in GM than in living environment with domination of A. tubingensis and A. welwitschiae. FB2- but not FB1- was confirmed via HPLC-MS and detection of fum1 and fum8 genes for one isolate of A. niger (0.015 μg/mL) and 8/15 isolates of A. welwitschiae (0.128–13.467 μg/mL). After 24 h, both FB1 and FB2 were weakly cytotoxic (MTT assay) to human lung A549 cells and THP-1 macrophage-like cells. In THP-1 cells FB1 but not FB2 provoked a higher increase of IL-8, TNF-α and IL-1β (ELISA). In A549 cells DNA damaging effect of FB1 was slightly higher than that of FB2 (Comet assay). In THP-1 macrophage-like cells A. tubingensis and A. piperis evoked immunomodulatory effects which corresponded to their cytotoxicity (IC50 = 0.228–0.323 mg/mL); A. welwitschiae, A. tubingensis and A. piperis exerted cytotoxic (IC50 = 0.214–0.460 mg/mL) and genotoxic effects in A549 cells. Presumably, secondary metabolites other than FB2 may have contributed to the toxicity of black Aspergilli.
Daniela Jakšić; Sándor Kocsubé; Ottó Bencsik; Anita Kecskeméti; András Szekeres; Dubravko Jelić; Nevenka Kopjar; Csaba Vágvölgyi; János Varga; Maja Šegvić Klarić. Fumonisin production and toxic capacity in airborne black Aspergilli. Toxicology in Vitro 2018, 53, 160 -171.
AMA StyleDaniela Jakšić, Sándor Kocsubé, Ottó Bencsik, Anita Kecskeméti, András Szekeres, Dubravko Jelić, Nevenka Kopjar, Csaba Vágvölgyi, János Varga, Maja Šegvić Klarić. Fumonisin production and toxic capacity in airborne black Aspergilli. Toxicology in Vitro. 2018; 53 ():160-171.
Chicago/Turabian StyleDaniela Jakšić; Sándor Kocsubé; Ottó Bencsik; Anita Kecskeméti; András Szekeres; Dubravko Jelić; Nevenka Kopjar; Csaba Vágvölgyi; János Varga; Maja Šegvić Klarić. 2018. "Fumonisin production and toxic capacity in airborne black Aspergilli." Toxicology in Vitro 53, no. : 160-171.
Maja Peraica; Dubravka Rašić; Daniela Jakšić Despot; Maja Šegvić Klarić. Oxidative stress in animals treated with ochratoxin A and citrinin and its reversal by resveratrol. Toxicology Letters 2017, 280, S198 .
AMA StyleMaja Peraica, Dubravka Rašić, Daniela Jakšić Despot, Maja Šegvić Klarić. Oxidative stress in animals treated with ochratoxin A and citrinin and its reversal by resveratrol. Toxicology Letters. 2017; 280 ():S198.
Chicago/Turabian StyleMaja Peraica; Dubravka Rašić; Daniela Jakšić Despot; Maja Šegvić Klarić. 2017. "Oxidative stress in animals treated with ochratoxin A and citrinin and its reversal by resveratrol." Toxicology Letters 280, no. : S198.
Daniela Jakšić Despot; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Biljana Nigović; Maja Šegvić Klarić. Frequency of sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-MET-STC)-producing airborne Aspergilli from flooded and unflooded area in Croatia. Toxicology Letters 2017, 280, S210 .
AMA StyleDaniela Jakšić Despot, Miranda Sertić, Ana Mornar Turk, Domagoj Kifer, Biljana Nigović, Maja Šegvić Klarić. Frequency of sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-MET-STC)-producing airborne Aspergilli from flooded and unflooded area in Croatia. Toxicology Letters. 2017; 280 ():S210.
Chicago/Turabian StyleDaniela Jakšić Despot; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Biljana Nigović; Maja Šegvić Klarić. 2017. "Frequency of sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-MET-STC)-producing airborne Aspergilli from flooded and unflooded area in Croatia." Toxicology Letters 280, no. : S210.
Aspergillus flavus is a filamentous fungus which is widespread on agricultural products and also able to cause various human diseases. This species is frequently isolated from indoor air as well, furthermore, it is known as a common causal agent of keratomycosis, particularly in subtropical and tropical areas. It is also able to produce aflatoxins, one of the most carcinogenic mycotoxins which are harmful to animals and humans. In this study, 59 A. flavus isolates from four different habitats and 1 A. minisclerotigenes isolate were investigated. The isolates were identified and confirmed at the species level by the sequence analysis of a part of their calmodulin gene. Applying a combined analysis of UP-PCR, microsatellite, and calmodulin sequence data, the four group of isolates formed separate clusters on the phylogenetic tree. Examining the distribution of mating type genes MAT1-1 and MAT1-2, a ratio of approximately 3:1 was determined, and no correlation was found between the carried mating type gene and the aflatoxin production capability. HPLC analysis revealed that none of the examined isolates collected from indoor air or maize in Central Europe were able to produce aflatoxins, while about half of the isolates from India produced these mycotoxins under the test conditions.
Nikolett Baranyi; Sándor Kocsubé; Daniela Jakšić Despot; Maja Šegvić Klarić; András Szekeres; Ottó Bencsik; Anita Kecskeméti; Palanisamy Manikandan; Beáta Tóth; Laszlo Kredics; Jamal M. Khaled; Naiyf S. Alharbi; Csaba Vágvölgyi; János Varga. Combined genotyping strategy reveals structural differences betweenAspergillus flavuslineages from different habitats impacting human health. Journal of Basic Microbiology 2017, 57, 899 -909.
AMA StyleNikolett Baranyi, Sándor Kocsubé, Daniela Jakšić Despot, Maja Šegvić Klarić, András Szekeres, Ottó Bencsik, Anita Kecskeméti, Palanisamy Manikandan, Beáta Tóth, Laszlo Kredics, Jamal M. Khaled, Naiyf S. Alharbi, Csaba Vágvölgyi, János Varga. Combined genotyping strategy reveals structural differences betweenAspergillus flavuslineages from different habitats impacting human health. Journal of Basic Microbiology. 2017; 57 (11):899-909.
Chicago/Turabian StyleNikolett Baranyi; Sándor Kocsubé; Daniela Jakšić Despot; Maja Šegvić Klarić; András Szekeres; Ottó Bencsik; Anita Kecskeméti; Palanisamy Manikandan; Beáta Tóth; Laszlo Kredics; Jamal M. Khaled; Naiyf S. Alharbi; Csaba Vágvölgyi; János Varga. 2017. "Combined genotyping strategy reveals structural differences betweenAspergillus flavuslineages from different habitats impacting human health." Journal of Basic Microbiology 57, no. 11: 899-909.