Ana Domijan | Faculty of Pharmacy and Biochemistry, University of Zagreb (original) (raw)

Papers by Ana Domijan

Research paper thumbnail of Impact of Anticoagulants on Assessment of Zinc in Plasma

Croatica Chemica Acta, 2018

The aim of this study was to compare zinc (Zn) level in EDTA, heparin, citrate plasma and serum. ... more The aim of this study was to compare zinc (Zn) level in EDTA, heparin, citrate plasma and serum. The blood samples from the same healthy volunteers (n = 10) were sampled by use of different anticoagulants (EDTA, heparin and citrate) or with no anticoagulant. Zn level was determined by flame atomic-absorption spectrometer (AAnalyst 800, PerkinElmer, USA). Zn level in EDTA, heparin, citrate plasma and serum was in reference range (0.7 to 1.5 μg mL-1), and the difference between sample groups was not observed (P = 0.079). However, correlation was observed only between Zn level in heparin plasma and citrate plasma (rs = 0.72; P = 0.016) and citrate plasma and serum (rs = 0.76; P = 0.012). In conclusion, in Zn blood analysis, sample collection step is important and should be observed when planning study and when comparing the results of Zn level from various studies.

Research paper thumbnail of Lactic acid bacteria isolated from equid milk and their extracellular metabolites show great probiotic properties and anti-inflammatory potential

International Dairy Journal

Research paper thumbnail of Cytotoxicity of gamma irradiated aflatoxin B1 and ochratoxin A

Journal of Environmental Science and Health, Part B

Toxicity of gamma irradiated mycotoxins aflatoxin B 1 (AFB 1) and ochratoxin A (OTA) was investig... more Toxicity of gamma irradiated mycotoxins aflatoxin B 1 (AFB 1) and ochratoxin A (OTA) was investigated in vitro. AFB 1 and OTA stock solutions (50 mM, in methanol) were gamma irradiated (5 and 10 kGy) and non-irradiated and irradiated mycotoxins solutions were tested for cytotoxicity on Pk15, HepG2 and SH-SY5Y cell lines (MTT assay, 1-500 lM concentration range; 24 h exposure). Degradation of mycotoxin molecules was examined by liquid chromatography tandem mass spectrometry (HPLC-MS/MS). AFB 1 and OTA radiolytic products were less toxic than the parent mycotoxins to all of the tested cell lines. Gamma irradiation even at 5 kGy had effect on AFB 1 and OTA molecules however, this effect was dependent on chemical structure of mycotoxin. Since gamma irradiation at low dose reduced initial level of both mycotoxins, and gamma irradiated mycotoxins had lower toxicity in comparison to non-irradiated mycotoxins, it can be concluded that gamma irradiation could be used as decontamination method.

Research paper thumbnail of Cytogenetic status and oxidative stress parameters in patients with thyroid diseases

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2016

Since the incidence of cancer has increased over the years, adequate prevention programmes are ne... more Since the incidence of cancer has increased over the years, adequate prevention programmes are needed. Thyroid cancer is one of the fastest growing cancer types in the world. In this study we performed a case-control study of 100 untreated patients with thyroid diseases (papillary thyroid cancer, follicular thyroid adenoma, and other thyroid diseases) and 100 control volunteers. Oxidative status differed among the two investigated groups. The patients' group had 1.60-fold higher concentrations of malondialdehyde and 1.26-fold higher concentrations of protein carbonyls. At the same time, the concentrations of glutathione and catalase activity were by 32% and 35% lower, respectively. A similar effect was observed for the cytogenetic status where higher comet assay tail intensity (1.84-fold) and the total numbers of chromosome aberrations (1.47-fold), micronuclei (2.32-fold), nucleoplasmic bridges (3.98-fold), and nuclear buds (2.34-fold) were detected. As for protein expression in thyroid tissue, 97.89% were positive for either B-Raf or Ret. Interestingly, the papillary thyroid cancer patients more frequently expressed B-Raf proteins compared to the follicular thyroid adenoma patients and patients with other thyroid diseases. Human biomonitoring studies enable a risk assessment of general population, such data could be used to identify risk subgroups.

Research paper thumbnail of Nalaz okratoksina A u plazmi zdravih ljudi u gradu Zagrebu

Research paper thumbnail of Ochratoxin A in blood of healthy population in Zagreb

Archives of Industrial Hygiene and Toxicology

Healthy blood donors from the city of Zagreb were checked for the presence of a nephrotoxic mycot... more Healthy blood donors from the city of Zagreb were checked for the presence of a nephrotoxic mycotoxin ochratoxin A (OTA) in the plasma. Samples of blood were collected in June, September, and December 1997, and March 1998, totalling 200 or 50 in each round. The concentrations of OTA were measured using high pressure liquid chromatography (HPLC) method (detection limit 0.2 ng OTA/ml of plasma). The frequency of OTA-positive samples (> 0.2 ng/ml of plasma) showed significant seasonal variation (P < 0.001). The frequency of OTA-positive samples was the highest in March (65%) and it gradually decreased towards December (12%). The high frequency of positive samples coincided with seasons favouring growth of moulds and production of toxins. The daily intake of OTA by healthy persons in Zagreb was estimated from the mean concentration of OTA in samples collected during the whole year (0.19 ng OTA/ml plasma). The estimated daily intake was 0.26 ng/kg b.w., that is, substantially below the tolerable daily intake proposed by World Health Organization (16.0 ng/kg b.w.).

Research paper thumbnail of Cytogenetic and oxidative status of human lymphocytes after exposure to clinically relevant concentrations of antimalarial drugs atovaquone and proguanil hydrochloride in vitro

Fundamental & Clinical Pharmacology, 2015

Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention a... more Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention and treatment of Plasmodium falciparum malaria. As safe and effective antimalarial drugs are needed in both the treatment and the prophylaxis of malaria, this study was performed to investigate their possible cyto/genotoxic potential towards human lymphocytes and the possible mechanism responsible for it. Two different concentrations of ATO and PROG were used with and without S9 metabolic activation. The concentrations used were those found in human plasma when a fixed-dose combination of ATO and PROG was used: 2950/130 ng/mL after prophylactic treatment and 11 800/520 ng/mL after treatment of malaria, respectively. Possible cellular and DNA-damaging effects were evaluated by cell viability and alkaline comet assays, while oxidative stress potential was evaluated by formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assay, in addition to measuring malondialdehyde and glutathione levels. According to our results, the ATO/PROG combination displayed only weak cyto/genotoxic potential towards human lymphocytes with no impact on oxidative stress parameters, suggesting that oxidative stress is not implicated in their mechanism of action towards human lymphocytes. Given that the key portion of the damaging effects was induced after S9 metabolic activation, it is to presume that the principal metabolite of PROG, cycloguanil, had the greatest impact. The obtained results indicate that the ATO/PROG combination is relatively safe for the consumption from the aspect of cyto/genotoxicity, especially if used for prophylactic treatment. Nevertheless, further cytogenetic research and regular patient monitoring are needed to minimize the risk of adverse events especially among frequent travellers.

Research paper thumbnail of Mould contamination and co-occurrence of mycotoxins in maize grain in Croatia

Acta pharmaceutica (Zagreb, Croatia), 2005

Maize grain samples (n=15) collected during the autumn of 2002 were analyzed for the presence of ... more Maize grain samples (n=15) collected during the autumn of 2002 were analyzed for the presence of moulds and mycotoxins fumonisin B1 (FB1), fumonisin B2 (FB2), zearalenone (ZEA), and ochratoxin A (OTA). Mycological analysis showed that all samples were contaminated with Fusarium spp. and Penicillium spp., while Aspergillus spp. were found in 5 samples. F. proliferatum and F. verticilloides, the producers of fumonisins, were found in 14 and 8 samples, respectively, while F. graminearum, the producer of ZEA, was present in all samples. The most frequent mycotoxins were FB1 (15/15) and ZEA (12/15), followed by OTA (7/15), while FB2 was found in only two samples. Seven samples were contaminated with two mycotoxins, seven with three, and one sample with only one mycotoxin. The concentrations (mean+/-SD) of FB1, ZEA, and OTA in positive samples were 459.5+/-314.6, 1.70+/-0.80, and 1.40+/-0.55 microg kg-1, respectively, and the concentrations of FB2 in two samples were 68.4 and 3084.0 micro...

Research paper thumbnail of In vitro genotoxicity of mycotoxins ochratoxin A and fumonisin B1 could be prevented by sodium copper chlorophyllin – Implication to their genotoxic mechanism

Food Chemistry, 2015

The aim of this study was to investigate the possible protective effect of sodium copper chloroph... more The aim of this study was to investigate the possible protective effect of sodium copper chlorophyllin (CHL) against cytotoxicity and DNA damage induced by mycotoxins ochratoxin A (OTA) and fumonisin B1 (FB1). CHL (0.1-100 μg/ml) alone had no impact on cell viability and genome damage in the primary human peripheral blood lymphocytes (HPBLs) and exhibited free radical scavenging activity in the DPPH assay. Both mycotoxins, OTA (4 μmol/l) and FB1 (20 μg/ml), induced DNA damage in HPBLs already after 1 h exposure. When the HPBLs were co-exposed to CHL (10 and 100 μg/ml) and OTA (4 μmol/l) or FB1 (20 μg/ml) for 1 h, CHL protected against cell and DNA damage induced by both mycotoxins, implying that OTA and FB1 cytogenotoxicity mechanisms function at least partially through oxidative stress. Therefore, CHL could be a perfect candidate for possible use as an antioxidant.

Research paper thumbnail of Fumonisin B1-induced apoptosis in rat liver: Morphometrical study

Research paper thumbnail of The effect of tretment with ochratoxin A on oxidative stress in rat liver and kidney

FEBS Workshop, 2009

Sažetak: Humans all round the World are continuously exposed to mycotoxin ochratoxin A (OTA) that... more Sažetak: Humans all round the World are continuously exposed to mycotoxin ochratoxin A (OTA) that frequently contaminates various foods and feeds. OTA is nephrotoxic, carcinogen and immunotoxic compound. It is known that the primary target organ of OTA toxicity in ...

Research paper thumbnail of Fumonisin B1: A Neurotoxic Mycotoxin / Fumonizin B1: Neurotoksični Mikotoksin

Archives of Industrial Hygiene and Toxicology, 2000

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predomi... more Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB1 is the most abundant and toxicologically the most significant one. FB1 has a wide range of toxic effects, depending on animal species. In horses FB1 causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB1 is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB1-contaminated maize-based food. However, possible involvement of FB1 in the development of human diseases is not clear. Neverthel...

Research paper thumbnail of Prevention of exposure to mycotoxins from food and feed

Arhiv za Higijenu Rada I …, 2002

Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origi... more Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origin. This paper gives a short review of the agronomical methods and food and feed storage recommendations for the prevention of mould contamination. It describes the practical methods of feed decontamination and the use of feed additives where mycotoxin contamination prevention has failed. However, these methods should be avoided as much as possible because they may increase the cost of production, reduce the nutritional value of feed, and leave residues of mycotoxins or their toxic metabolites. Since there is no universal and reliable method of feed decontamination for all mycotoxins, the paper stresses the importance of preventive measures.

Research paper thumbnail of Mikotoksini u hrani i njihov učinak na ljudsko zdravlje

Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They a... more Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They are produced by various strains of moulds, particularly in tropical countries. Due to significant trade of cereals, humans in temperate countries can also be exposed to mycotoxins. The most common route of exposure to mycotoxins is ingestion, but it may also involve dermal, respiratory, and parenteral routes, the last being associated with drug abuse. Apart from acute and chronic toxic effects on human health called mycotoxicosis, some mycotoxins are proved or suspected human carcinogens. This paper describes various human diseases caused by ergot, aflatoxin, ochratoxin A, 3-nitropropionic acid, trichothecene, zearalenone, and fumonisin. It also gives a quick review of human carcinogenicity evaluations of the International Agency for Research on Cancer and of regulatory limits of mycotoxin concentrations in various commodities.

Research paper thumbnail of Contamination of food with mycotoxins and human health

Archives of Industrial Hygiene and Toxicology

Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They a... more Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They are produced by various strains of moulds, particularly in tropical countries. Due to significant trade of cereals, humans in temperate countries can also be exposed to mycotoxins. The most common route of exposure to mycotoxins is ingestion, but it may also involve dermal, respiratory, and parenteral routes, the last being associated with drug abuse. Apart from acute and chronic toxic effects on human health called mycotoxicosis, some mycotoxins are proved or suspected human carcinogens. This paper describes various human diseases caused by ergot, afflatoxin, ochratoxin A, 3-nitropropionic acid, trichothecene, zearalenone, and fumonisin. It also gives a quick review of human carcinogenicity evaluations of the international Agency for Research on Cancer and of regulatory limits of mycotoxin concentrations in various commodities.

Research paper thumbnail of Ochratoxin A in wine

Archives of Industrial Hygiene and Toxicology

A high-performance liquid chromatography (HPLC) method for determination of ochratoxin A (OTA) in... more A high-performance liquid chromatography (HPLC) method for determination of ochratoxin A (OTA) in wine was developed and checked on 14 samples of wine produced in the Republic of Croatia. OTA detection in red and white wine was validated checking the linearity of the method (r2=0.997 and 0.999, respectively), recovery (88 and 95 %, respectively), and precision (RSD=3.1 and 1.4 %, respectively). The detection limit of OTA in both red and white wine was 10 ng L(-1). The OTA concentration in all red wines was above the detection limit (mean 22+/-11 ng L(-1)), while only 4 of 7 white wines contained OTA (mean 10+/-9 ng L(-1)). Three OTA-free white wines were from the north of Croatia (inland), while all wines produced in the south (Adriatic coast) were OTA-positive. However, the concentrations were too low to present a risk for a moderate wine consumer.

Research paper thumbnail of Kontaminiranost kukuruza u Hrvatskoj plijesnima i nekim mikotoksinima

Maize grain samples (n = 15) collected during the autumn of 2002 were analyzed for the presence o... more Maize grain samples (n = 15) collected during the autumn of 2002 were analyzed for the presence of moulds and mycotoxins fumonisin B1 (FB1), fumonisin B2 (FB2), zearalenone (ZEA), and ochratoxin A (OTA). Mycological analysis showed that all samples were contaminated with Fusarium spp. and Penicillium spp., while Aspergillus spp. were found in 5 samples. F. proliferatum and F. verticilloides, the producers of fumonisins, were found in 14 and 8 samples, respectively, while F. graminearum, the producer of ZEA, was present in all samples. The most frequent mycotoxins were FB1 (15/15) and ZEA (12/15), followed by OTA (7/15), while FB2 was found in only two samples. Seven samples were contaminated with two mycotoxins, seven with three, and one sample with only one mycotoxin. The concentrations (mean ± SD) of FB1, ZEA, and OTA in positive samples were 459.5 ± 314.6, 1.70 ± 0.80, and 1.40 ± 0.55 microgram kg-1, respectively, and the concentrations of FB2 in two samples were 68.4 and 3084.0 ...

Research paper thumbnail of Reduction of ochratoxin A in dry-cured meat products using gamma-irradiation

Food Additives & Contaminants: Part A, 2015

The aim of this study was to investigate the efficiency of gamma (γ) irradiation in the reduction... more The aim of this study was to investigate the efficiency of gamma (γ) irradiation in the reduction of ochratoxin A (OTA) present in dry-cured meat products prepared from intentionally contaminated raw materials from OTA-treated pigs. OTA concentrations determined in the samples (n=24) ranged from 25.8 μg/kg in bacon to 17.8 μg/kg in smoked ham. After γ-irradiation at doses of 3, 7 and 10 kGy (i.e. the doses used in the food industry), a dose-depended OTA reduction was observed, however not statistically significant. The Downloaded by [Croatian Veterinary Institute] at 04:25 25 May 2015

Research paper thumbnail of Malondialdehyde and 8-oxo-7.8-dihydro-2'deoxyguanosine in the urine of residents from Balkan endemic nephropathy area in Croatia--a pilot study

Collegium antropologicum, 2013

Balkan endemic nephropathy (BEN) is a human chronic tubulointerstitial renal disease that occurs ... more Balkan endemic nephropathy (BEN) is a human chronic tubulointerstitial renal disease that occurs in rural areas of some Balkan countries. The disease is insidious and fatal, and mostly affects persons in their sixties or seventies. BEN areas have unusually high rates of otherwise rare upper urinary tract tumors (UTT). Since extensive production of reactive oxygen species leading to oxidative stress has been implicated in tumor development, the aim of this study was to see whether oxidative stress is involved in the development of BEN and UTT. Urine samples were collected from a BEN village (N = 22) and a control village (N = 16) residents and analyzed for malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG). The levels of both oxidative stress parameters were significantly higher in the BEN village residents than controls. However, there was no correlation between MDA and 8-oxodG results. Our results confirm that oxidative stress could be implicated in developm...

Research paper thumbnail of Prevention of exposure to mycotoxins from food and feed

Arhiv za higijenu rada i toksikologiju, 2002

Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origi... more Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origin. This paper gives a short review of the agronomical methods and food and feed storage recommendations for the prevention of mould contamination. It describes the practical methods of feed decontamination and the use of feed additives where mycotoxin contamination prevention has failed. However, these methods should be avoided as much as possible because they may increase the cost of production, reduce the nutritional value of feed, and leave residues of mycotoxins or their toxic metabolites. Since there is no universal and reliable method of feed decontamination for all mycotoxins, the paper stresses the importance of preventive measures.

Research paper thumbnail of Impact of Anticoagulants on Assessment of Zinc in Plasma

Croatica Chemica Acta, 2018

The aim of this study was to compare zinc (Zn) level in EDTA, heparin, citrate plasma and serum. ... more The aim of this study was to compare zinc (Zn) level in EDTA, heparin, citrate plasma and serum. The blood samples from the same healthy volunteers (n = 10) were sampled by use of different anticoagulants (EDTA, heparin and citrate) or with no anticoagulant. Zn level was determined by flame atomic-absorption spectrometer (AAnalyst 800, PerkinElmer, USA). Zn level in EDTA, heparin, citrate plasma and serum was in reference range (0.7 to 1.5 μg mL-1), and the difference between sample groups was not observed (P = 0.079). However, correlation was observed only between Zn level in heparin plasma and citrate plasma (rs = 0.72; P = 0.016) and citrate plasma and serum (rs = 0.76; P = 0.012). In conclusion, in Zn blood analysis, sample collection step is important and should be observed when planning study and when comparing the results of Zn level from various studies.

Research paper thumbnail of Lactic acid bacteria isolated from equid milk and their extracellular metabolites show great probiotic properties and anti-inflammatory potential

International Dairy Journal

Research paper thumbnail of Cytotoxicity of gamma irradiated aflatoxin B1 and ochratoxin A

Journal of Environmental Science and Health, Part B

Toxicity of gamma irradiated mycotoxins aflatoxin B 1 (AFB 1) and ochratoxin A (OTA) was investig... more Toxicity of gamma irradiated mycotoxins aflatoxin B 1 (AFB 1) and ochratoxin A (OTA) was investigated in vitro. AFB 1 and OTA stock solutions (50 mM, in methanol) were gamma irradiated (5 and 10 kGy) and non-irradiated and irradiated mycotoxins solutions were tested for cytotoxicity on Pk15, HepG2 and SH-SY5Y cell lines (MTT assay, 1-500 lM concentration range; 24 h exposure). Degradation of mycotoxin molecules was examined by liquid chromatography tandem mass spectrometry (HPLC-MS/MS). AFB 1 and OTA radiolytic products were less toxic than the parent mycotoxins to all of the tested cell lines. Gamma irradiation even at 5 kGy had effect on AFB 1 and OTA molecules however, this effect was dependent on chemical structure of mycotoxin. Since gamma irradiation at low dose reduced initial level of both mycotoxins, and gamma irradiated mycotoxins had lower toxicity in comparison to non-irradiated mycotoxins, it can be concluded that gamma irradiation could be used as decontamination method.

Research paper thumbnail of Cytogenetic status and oxidative stress parameters in patients with thyroid diseases

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2016

Since the incidence of cancer has increased over the years, adequate prevention programmes are ne... more Since the incidence of cancer has increased over the years, adequate prevention programmes are needed. Thyroid cancer is one of the fastest growing cancer types in the world. In this study we performed a case-control study of 100 untreated patients with thyroid diseases (papillary thyroid cancer, follicular thyroid adenoma, and other thyroid diseases) and 100 control volunteers. Oxidative status differed among the two investigated groups. The patients' group had 1.60-fold higher concentrations of malondialdehyde and 1.26-fold higher concentrations of protein carbonyls. At the same time, the concentrations of glutathione and catalase activity were by 32% and 35% lower, respectively. A similar effect was observed for the cytogenetic status where higher comet assay tail intensity (1.84-fold) and the total numbers of chromosome aberrations (1.47-fold), micronuclei (2.32-fold), nucleoplasmic bridges (3.98-fold), and nuclear buds (2.34-fold) were detected. As for protein expression in thyroid tissue, 97.89% were positive for either B-Raf or Ret. Interestingly, the papillary thyroid cancer patients more frequently expressed B-Raf proteins compared to the follicular thyroid adenoma patients and patients with other thyroid diseases. Human biomonitoring studies enable a risk assessment of general population, such data could be used to identify risk subgroups.

Research paper thumbnail of Nalaz okratoksina A u plazmi zdravih ljudi u gradu Zagrebu

Research paper thumbnail of Ochratoxin A in blood of healthy population in Zagreb

Archives of Industrial Hygiene and Toxicology

Healthy blood donors from the city of Zagreb were checked for the presence of a nephrotoxic mycot... more Healthy blood donors from the city of Zagreb were checked for the presence of a nephrotoxic mycotoxin ochratoxin A (OTA) in the plasma. Samples of blood were collected in June, September, and December 1997, and March 1998, totalling 200 or 50 in each round. The concentrations of OTA were measured using high pressure liquid chromatography (HPLC) method (detection limit 0.2 ng OTA/ml of plasma). The frequency of OTA-positive samples (> 0.2 ng/ml of plasma) showed significant seasonal variation (P < 0.001). The frequency of OTA-positive samples was the highest in March (65%) and it gradually decreased towards December (12%). The high frequency of positive samples coincided with seasons favouring growth of moulds and production of toxins. The daily intake of OTA by healthy persons in Zagreb was estimated from the mean concentration of OTA in samples collected during the whole year (0.19 ng OTA/ml plasma). The estimated daily intake was 0.26 ng/kg b.w., that is, substantially below the tolerable daily intake proposed by World Health Organization (16.0 ng/kg b.w.).

Research paper thumbnail of Cytogenetic and oxidative status of human lymphocytes after exposure to clinically relevant concentrations of antimalarial drugs atovaquone and proguanil hydrochloride in vitro

Fundamental & Clinical Pharmacology, 2015

Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention a... more Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention and treatment of Plasmodium falciparum malaria. As safe and effective antimalarial drugs are needed in both the treatment and the prophylaxis of malaria, this study was performed to investigate their possible cyto/genotoxic potential towards human lymphocytes and the possible mechanism responsible for it. Two different concentrations of ATO and PROG were used with and without S9 metabolic activation. The concentrations used were those found in human plasma when a fixed-dose combination of ATO and PROG was used: 2950/130 ng/mL after prophylactic treatment and 11 800/520 ng/mL after treatment of malaria, respectively. Possible cellular and DNA-damaging effects were evaluated by cell viability and alkaline comet assays, while oxidative stress potential was evaluated by formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assay, in addition to measuring malondialdehyde and glutathione levels. According to our results, the ATO/PROG combination displayed only weak cyto/genotoxic potential towards human lymphocytes with no impact on oxidative stress parameters, suggesting that oxidative stress is not implicated in their mechanism of action towards human lymphocytes. Given that the key portion of the damaging effects was induced after S9 metabolic activation, it is to presume that the principal metabolite of PROG, cycloguanil, had the greatest impact. The obtained results indicate that the ATO/PROG combination is relatively safe for the consumption from the aspect of cyto/genotoxicity, especially if used for prophylactic treatment. Nevertheless, further cytogenetic research and regular patient monitoring are needed to minimize the risk of adverse events especially among frequent travellers.

Research paper thumbnail of Mould contamination and co-occurrence of mycotoxins in maize grain in Croatia

Acta pharmaceutica (Zagreb, Croatia), 2005

Maize grain samples (n=15) collected during the autumn of 2002 were analyzed for the presence of ... more Maize grain samples (n=15) collected during the autumn of 2002 were analyzed for the presence of moulds and mycotoxins fumonisin B1 (FB1), fumonisin B2 (FB2), zearalenone (ZEA), and ochratoxin A (OTA). Mycological analysis showed that all samples were contaminated with Fusarium spp. and Penicillium spp., while Aspergillus spp. were found in 5 samples. F. proliferatum and F. verticilloides, the producers of fumonisins, were found in 14 and 8 samples, respectively, while F. graminearum, the producer of ZEA, was present in all samples. The most frequent mycotoxins were FB1 (15/15) and ZEA (12/15), followed by OTA (7/15), while FB2 was found in only two samples. Seven samples were contaminated with two mycotoxins, seven with three, and one sample with only one mycotoxin. The concentrations (mean+/-SD) of FB1, ZEA, and OTA in positive samples were 459.5+/-314.6, 1.70+/-0.80, and 1.40+/-0.55 microg kg-1, respectively, and the concentrations of FB2 in two samples were 68.4 and 3084.0 micro...

Research paper thumbnail of In vitro genotoxicity of mycotoxins ochratoxin A and fumonisin B1 could be prevented by sodium copper chlorophyllin – Implication to their genotoxic mechanism

Food Chemistry, 2015

The aim of this study was to investigate the possible protective effect of sodium copper chloroph... more The aim of this study was to investigate the possible protective effect of sodium copper chlorophyllin (CHL) against cytotoxicity and DNA damage induced by mycotoxins ochratoxin A (OTA) and fumonisin B1 (FB1). CHL (0.1-100 μg/ml) alone had no impact on cell viability and genome damage in the primary human peripheral blood lymphocytes (HPBLs) and exhibited free radical scavenging activity in the DPPH assay. Both mycotoxins, OTA (4 μmol/l) and FB1 (20 μg/ml), induced DNA damage in HPBLs already after 1 h exposure. When the HPBLs were co-exposed to CHL (10 and 100 μg/ml) and OTA (4 μmol/l) or FB1 (20 μg/ml) for 1 h, CHL protected against cell and DNA damage induced by both mycotoxins, implying that OTA and FB1 cytogenotoxicity mechanisms function at least partially through oxidative stress. Therefore, CHL could be a perfect candidate for possible use as an antioxidant.

Research paper thumbnail of Fumonisin B1-induced apoptosis in rat liver: Morphometrical study

Research paper thumbnail of The effect of tretment with ochratoxin A on oxidative stress in rat liver and kidney

FEBS Workshop, 2009

Sažetak: Humans all round the World are continuously exposed to mycotoxin ochratoxin A (OTA) that... more Sažetak: Humans all round the World are continuously exposed to mycotoxin ochratoxin A (OTA) that frequently contaminates various foods and feeds. OTA is nephrotoxic, carcinogen and immunotoxic compound. It is known that the primary target organ of OTA toxicity in ...

Research paper thumbnail of Fumonisin B1: A Neurotoxic Mycotoxin / Fumonizin B1: Neurotoksični Mikotoksin

Archives of Industrial Hygiene and Toxicology, 2000

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predomi... more Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB1 is the most abundant and toxicologically the most significant one. FB1 has a wide range of toxic effects, depending on animal species. In horses FB1 causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB1 is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB1-contaminated maize-based food. However, possible involvement of FB1 in the development of human diseases is not clear. Neverthel...

Research paper thumbnail of Prevention of exposure to mycotoxins from food and feed

Arhiv za Higijenu Rada I …, 2002

Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origi... more Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origin. This paper gives a short review of the agronomical methods and food and feed storage recommendations for the prevention of mould contamination. It describes the practical methods of feed decontamination and the use of feed additives where mycotoxin contamination prevention has failed. However, these methods should be avoided as much as possible because they may increase the cost of production, reduce the nutritional value of feed, and leave residues of mycotoxins or their toxic metabolites. Since there is no universal and reliable method of feed decontamination for all mycotoxins, the paper stresses the importance of preventive measures.

Research paper thumbnail of Mikotoksini u hrani i njihov učinak na ljudsko zdravlje

Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They a... more Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They are produced by various strains of moulds, particularly in tropical countries. Due to significant trade of cereals, humans in temperate countries can also be exposed to mycotoxins. The most common route of exposure to mycotoxins is ingestion, but it may also involve dermal, respiratory, and parenteral routes, the last being associated with drug abuse. Apart from acute and chronic toxic effects on human health called mycotoxicosis, some mycotoxins are proved or suspected human carcinogens. This paper describes various human diseases caused by ergot, aflatoxin, ochratoxin A, 3-nitropropionic acid, trichothecene, zearalenone, and fumonisin. It also gives a quick review of human carcinogenicity evaluations of the International Agency for Research on Cancer and of regulatory limits of mycotoxin concentrations in various commodities.

Research paper thumbnail of Contamination of food with mycotoxins and human health

Archives of Industrial Hygiene and Toxicology

Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They a... more Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They are produced by various strains of moulds, particularly in tropical countries. Due to significant trade of cereals, humans in temperate countries can also be exposed to mycotoxins. The most common route of exposure to mycotoxins is ingestion, but it may also involve dermal, respiratory, and parenteral routes, the last being associated with drug abuse. Apart from acute and chronic toxic effects on human health called mycotoxicosis, some mycotoxins are proved or suspected human carcinogens. This paper describes various human diseases caused by ergot, afflatoxin, ochratoxin A, 3-nitropropionic acid, trichothecene, zearalenone, and fumonisin. It also gives a quick review of human carcinogenicity evaluations of the international Agency for Research on Cancer and of regulatory limits of mycotoxin concentrations in various commodities.

Research paper thumbnail of Ochratoxin A in wine

Archives of Industrial Hygiene and Toxicology

A high-performance liquid chromatography (HPLC) method for determination of ochratoxin A (OTA) in... more A high-performance liquid chromatography (HPLC) method for determination of ochratoxin A (OTA) in wine was developed and checked on 14 samples of wine produced in the Republic of Croatia. OTA detection in red and white wine was validated checking the linearity of the method (r2=0.997 and 0.999, respectively), recovery (88 and 95 %, respectively), and precision (RSD=3.1 and 1.4 %, respectively). The detection limit of OTA in both red and white wine was 10 ng L(-1). The OTA concentration in all red wines was above the detection limit (mean 22+/-11 ng L(-1)), while only 4 of 7 white wines contained OTA (mean 10+/-9 ng L(-1)). Three OTA-free white wines were from the north of Croatia (inland), while all wines produced in the south (Adriatic coast) were OTA-positive. However, the concentrations were too low to present a risk for a moderate wine consumer.

Research paper thumbnail of Kontaminiranost kukuruza u Hrvatskoj plijesnima i nekim mikotoksinima

Maize grain samples (n = 15) collected during the autumn of 2002 were analyzed for the presence o... more Maize grain samples (n = 15) collected during the autumn of 2002 were analyzed for the presence of moulds and mycotoxins fumonisin B1 (FB1), fumonisin B2 (FB2), zearalenone (ZEA), and ochratoxin A (OTA). Mycological analysis showed that all samples were contaminated with Fusarium spp. and Penicillium spp., while Aspergillus spp. were found in 5 samples. F. proliferatum and F. verticilloides, the producers of fumonisins, were found in 14 and 8 samples, respectively, while F. graminearum, the producer of ZEA, was present in all samples. The most frequent mycotoxins were FB1 (15/15) and ZEA (12/15), followed by OTA (7/15), while FB2 was found in only two samples. Seven samples were contaminated with two mycotoxins, seven with three, and one sample with only one mycotoxin. The concentrations (mean ± SD) of FB1, ZEA, and OTA in positive samples were 459.5 ± 314.6, 1.70 ± 0.80, and 1.40 ± 0.55 microgram kg-1, respectively, and the concentrations of FB2 in two samples were 68.4 and 3084.0 ...

Research paper thumbnail of Reduction of ochratoxin A in dry-cured meat products using gamma-irradiation

Food Additives & Contaminants: Part A, 2015

The aim of this study was to investigate the efficiency of gamma (γ) irradiation in the reduction... more The aim of this study was to investigate the efficiency of gamma (γ) irradiation in the reduction of ochratoxin A (OTA) present in dry-cured meat products prepared from intentionally contaminated raw materials from OTA-treated pigs. OTA concentrations determined in the samples (n=24) ranged from 25.8 μg/kg in bacon to 17.8 μg/kg in smoked ham. After γ-irradiation at doses of 3, 7 and 10 kGy (i.e. the doses used in the food industry), a dose-depended OTA reduction was observed, however not statistically significant. The Downloaded by [Croatian Veterinary Institute] at 04:25 25 May 2015

Research paper thumbnail of Malondialdehyde and 8-oxo-7.8-dihydro-2'deoxyguanosine in the urine of residents from Balkan endemic nephropathy area in Croatia--a pilot study

Collegium antropologicum, 2013

Balkan endemic nephropathy (BEN) is a human chronic tubulointerstitial renal disease that occurs ... more Balkan endemic nephropathy (BEN) is a human chronic tubulointerstitial renal disease that occurs in rural areas of some Balkan countries. The disease is insidious and fatal, and mostly affects persons in their sixties or seventies. BEN areas have unusually high rates of otherwise rare upper urinary tract tumors (UTT). Since extensive production of reactive oxygen species leading to oxidative stress has been implicated in tumor development, the aim of this study was to see whether oxidative stress is involved in the development of BEN and UTT. Urine samples were collected from a BEN village (N = 22) and a control village (N = 16) residents and analyzed for malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG). The levels of both oxidative stress parameters were significantly higher in the BEN village residents than controls. However, there was no correlation between MDA and 8-oxodG results. Our results confirm that oxidative stress could be implicated in developm...

Research paper thumbnail of Prevention of exposure to mycotoxins from food and feed

Arhiv za higijenu rada i toksikologiju, 2002

Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origi... more Mycotoxins are metabolites of moulds that may be found in food and feed of plant and animal origin. This paper gives a short review of the agronomical methods and food and feed storage recommendations for the prevention of mould contamination. It describes the practical methods of feed decontamination and the use of feed additives where mycotoxin contamination prevention has failed. However, these methods should be avoided as much as possible because they may increase the cost of production, reduce the nutritional value of feed, and leave residues of mycotoxins or their toxic metabolites. Since there is no universal and reliable method of feed decontamination for all mycotoxins, the paper stresses the importance of preventive measures.