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Mechanisms of aging, and cancer as one of main associated pathology are only on verge of understanding. Even in healthy aging gradually loss of function in excretion organs kidneys and liver appears. Previously, we did not find expected elevated tissue concentrations of reactive oxidative species (ROS), that are assumed to be present in old humans and experimental animals and that they can be reversed by antioxidants (AO) treatment. The new hypothesis was that the expression of ROS inducible, potent antioxidant and metal scavenging proteins, metallothioneins Mt1 and Mt2 (MTs), among others, increases in old age to maintain ROS levels and that they can be further modulated with AO. To that aim we studied male and female Wistar rats regularly aged together with these treated with melatonin and resveratrol. Starting from 3 months of age, for the next 9 or 21 months treated rats were drinking AO in water (~1 mg/kg b.w./day), whereas the control animals were drinking water or AO vehicle (0.01% ethanol). Trace elements (TE) were analysed by ICP-MS and the expression of MTs mRNA and proteins in kidneys and liver were determinate by end-point RT-PCR and immunochemical methods, respectively. AO did not change TE accumulation and expression of MTs in both sexes, but known iron accumulation in aged animals was followed by copper and toxic metal cadmium with known female domination. After 1 year, aging increased MTs expression in both sexes that did only slightly further increased after 2 years. We conclude that Fenton reactive metals accumulated in aged animals may influence MTs mRNA and protein expression to help retain physiological ROS level in old rats. (Croatian Science Foundation project IP-2013-11-1481).

Aspergilli section Nidulantes series Versicolores, producers of the mycotoxin sterigmatocystin (STC), dominated the fungi isolated from air and dust in flood-affected homes (Gunja) and control houses (Gornji Stupnik) in Croatia. The majority of isolates were able to produce STC and some isolates also produced its derivate 5- methoxysterigmatocystin (5-MET-STC). How can this affect human health? Here we present: a) Aspergilli series Versicolores species diversity in air and dust (calmodulin sequence-based methods) ; b) occurrence of STC and metabolites from the STC biosynthesis pathway in dust (LC- MS/MS) ; and c) immunomodulatory and genotoxic effects of STC and 5-MET-STC in lungs of male Wistar rats upon intratracheal instillation in concentrations found in dust. Most of the Versicolores isolates were from Gunja (91/125). Most isolates belonging to A. jensenii, A. creber, A. puulaauensis, A. tennesseensis, A. venenatus produced both STC and 5-MET-STC. A. amoenus, A. fructus, A. griseoaurantiacus, A. pepii and A. protuberus produced STC but not 5-MET-STC, while A. sydowii did not produce any of these two toxins. Among the 75 fungal compounds detected in dust, metabolites from the STC pathway including STC, 5-MET-STC, veriscolorin C, averufin and averantin were among the most abundant metabolites, which prevailed in repaired houses in Gunja. The highest concentrations of STC (0.59 µg/g) and 5-MET-STC (7.70 µg/g) in dust were detected in Gunja. In rat lungs, the immunomodulatory effects of STC (0.4 µg/mL) and 5- MET-STC (5 µg/mL) were insignificant. The levels of DNA damage were similar although STC was applied at a 10-fold lower dose. The results of combined treatment suggested possible antagonistic interactions. This work was fully supported by the Croatian Science Foundation under the project MycotoxA (IP-09-2014-5982).

Human studies on oxidative stress induced by general anaesthesia are rather scarce. It is important to study effects of anaesthetics on oxidative stress, particularly in surgical procedures with high ROS production, because their effect may be pivotal for the outcome of the surgery. In the presented study, patients with hydronephrosis underwent balanced anaesthesia or Total Intravenous Anaesthesia (TIVA) with target- controlled infusion (TCI) during surgery. Blood samples from patients (N=32) were taken before induction of anaesthesia, 30 minutes and 24 hours after beginning of the surgery. Measured parameters of oxidative stress were compared between two types of anaesthesia. Malondialdehyde (MDA) was measured using HPLC with fluorescence detector. Glutathione (GSH), reactive oxygen species (ROS), total antioxidant capacity (TOC) and protein carbonyl concentration were measured spectrophotometrically. Activity of superoxide dismutase (SOD) was measured spectrophotometrically using commercial kits. Observed data were analysed by mixed modelling with oxidative stress parameter as a dependent variable and sampling time nested within an anaesthetic group as fixed effects, and subject id as a random effect. Post-hoc were performed and the false discovery rate was controlled by the Benjamini-Hochberg method. SOD activity was significantly higher in patients that underwent balanced anaesthesia than anaesthesia with TIVA/TCI 30 minutes after beginning of the surgery. There was no statistically significant difference in other measured parameters between balanced and TIVA/TCI type of anaesthesia. Results of the majority of the measured parameters of oxidative stress were significantly different 30 minutes or 24 hours after the surgery from those measured before the anaesthesia (balanced and TIVA/ TCI). Results from this study contribute to general knowledge about oxidative stress caused by anaesthesia as an important factor in causing higher rates of postoperative complications and delayed recovery after surgery.

Sterigmatocystin (STC), a precursor of aflatoxin B1, is mycotoxin which International Agency for Research on Cancer evaluated as Group 2B. STC was isolated in 1954 from Aspergillus versicolor and afterwards from other Aspergillus species producing it as aflatoxin B1 precursor or as final mycotoxin. Due to its structural similarity to carcinogen AFB1, STC carcinogenic potential was studied much more than its toxicity. The aim of this study was to evaluate the effect of STC on antioxidative enzymes and heat shock proteins (Hsp 70 and Hsp27) as parameters of oxidative stress. Male Wistar rats (N=5 per group) were treated with single oral STC doses of 1/16, 1/8, and 1/4 of LD50 (10, 20 and 40 mg kg-1 b.w.). Control group was treated with corn oil which was used as STC vehicle. Catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in plasma, kidneys and liver were measured on a plate reader using commercial kits. Expressions of heat shock proteins Hsp70 i Hsp27 were measured in kidneys and liver using Western blot methods. CAT activity did not change in organs of treated animals. GPx activity was significantly lower in liver of rats treated with 1/8 and 1/4 LD50. Activity of SOD was significantly increased in kidneys of rats given 1/16 and 1/4 LD50. Expression of Hsp70 was significantly increased in liver samples of rats treated with 1/16 LD50 ; in kidneys the same dose augmented expression of Hsp70 but without significant difference to control group. Highest STC dose returned Hsp70 expression to control values. Expression of Hsp27 in liver and kidneys was not significantly changed at any STC dose. Taken together our findings suggest that acute oral exposure to STC causes oxidative stress both in liver and kidneys.

Water is the most abundant molecule in living cells. Aquaporin protein channels (AQPs) facilitate the passive movement of water across cell membranes. In mammalian kidneys, AQP1 and AQP2 facilitate water reabsorption from primary urine across the apical membrane of proximal and distal nephron tubules. Studies indicate that renal functional/structural changes in humans and experimental animals develop with age. Aging promotes fluid loss in tissues which was suggested to reflect changes in the expression/activity of AQPs. Here we investigated the potential age-ameliorating effects of two potential geroprotector substances, melatonin (endogenous hormone) and resveratrol (plant flavonoid), on AQP1 and AQP2 expressions in the rat model of experimental aging. During 21 months, rats of both sexes were given melatonin or resveratrol via drinking water (~1 mg/kg b.w./day), whereas control animals drank vehicle (0.01% ethanol in drinking water). The expression of both AQPs in the kidneys of control and treated animals was determined using immunofluorescence cytochemistry in tissue cryosections and Western blot analysis in isolated cell membranes. Results showed that melatonin and resveratrol treatment had no effect on renal AQP1 expression in both sexes. AQP2 expression in male and female kidneys of resveratrol-treated rats also did not change compared to controls. However, only in female rats, AQP2 expression was upregulated by melatonin in the inner stripe and papilla kidney regions. Therefore, in 24-month old rat kidneys, chronic oral intake of melatonin and resveratrol had no effect on AQP1, whereas melatonin exerted sex-dependent upregulation of AQP2. (Supported by Croatian Science Foundation project IP-2013-11-1481).

Telomeres are the main guardians of genome stability. During DNA replication, progressive shortening of telomeres takes place with each cell division. Critically short telomeres induce cell cycle arrest or apoptosis. Oxidative stress also plays an important role in telomere dynamics. Recent evidence highlights direct molecular connection between telomere attrition and mitochondrial dysfunction. Although reactive oxygen species (ROS) are normal products in intermediary metabolism, and are crucial for different intracellular signalling pathways, a disbalance resulting in ROS excess induces oxidative stress and accelerates telomere shortening. It is assumed that with ageing, production of ROS may be increased causing faster telomere shortening, and that both may be ameliorated by antioxidants. To test this hypothesis, we treated male and female Wistar rats for 9 or 21 months with melatonin and resveratrol and investigated their effect on telomere attrition rate in liver and kidney (various zones) tissues. Telomere length was assessed by Southern blotting of genomic DNA. The results in 1- and 2- year-old male and female rats showed an absence of significant differences in telomere length in the tissues from both organs after treatment with antioxidants compared to control (vehicle-treated) animals (N=4 per group). Based on obtained results, we did not observe beneficial properties of tested antioxidants towards age-dependent telomere shortening.

Levels of elements in brown bear (Ursus arctos) blood are unknown. Previously, we discovered that brown bears in Croatia have the highest tissue levels of toxic metals among hunted terrestrial wild mammals. However, associations with other related biomarkers of exposure and/or effect have not been studied. Considering that oxidative stress has been suggested as one of the pathways of toxic damage caused by metals, its biomarkers could be useful indicators of metal-related health effects. Our aim was to study biomarkers of oxidative stress (lipid peroxidation, antioxidative enzyme SOD activity) and metal exposure, (metallothionein, MT), in association with toxic metal levels in the blood of free- living brown bears from Croatia (N=8) and Poland (N=11). Metal content was measured using ICP- MS, products of lipid peroxidation (malondialdehyde, MDA) using HPLC, activity of antioxidative enzyme using spectrophotometry, and MT using differential pulse voltammetry. Median (range) mass fractions of cadmium (Cd) and mercury (Hg) in brown bear blood were 0.356 (0.110-1.34) and 7.23 (1.09-13.5) µg/kg, and showed no differences between the two populations, as well as MDA and MT. On the contrary, lead (Pb) was higher (p=0.041) in the Polish (median 145 ; range 104-192 µg/kg) compared to the Croatian (101 ; 58.9-184 µg/kg) bears, while SOD activity was lower (p=0.007) in the Polish (738 ; 21.6-2328 U/L) than in the Croatian (1428 ; 1008-2326 U/L) bears. Age, gender and season of collection had no significant influence on the measured parameters. Results present valuable contribution to toxicological studies of European brown bear and the first data describing metals and biomarkers in the blood of this species.

Statins are drugs widely used to treat hypercholesterolemia and reduce the risk of cardiovascular morbidity and mortality in patients with coronary heart disease. The mechanism of their action may be the inhibition of oxidant formation and blocking the effects of reactive oxygen species (ROS). As reported in recent studies, rosuvastatin has a beneficial effect on the plasma lipid profile and can reduce serum cholesterol and ROS formation in diabetic patients. The aim of this work was to determine the influence of rosuvastatin on the prooxidant- antioxidant balance in rat kidneys. This study was performed on male normolipidemic Wistar rats (N=36) divided into two control (treated with saline 5 mg kg-1 per day) and two experimental rosuvastatin-treated (5 and 10 mg kg-1 per day) groups. Animals were treated orally for 21 days. Malondialdehyde (MDA) – parameter of lipid peroxidation was measured in the kidney tissue homogenate of control and treated animals using the method by Drury et al. (1997). Data were analysed using t-test. Results are expressed as Mean±STD. MDA concentration was significantly lower in both experimental groups compared to controls: 0.41±0.05 vs. 0.62±0.08 µmol g-1 tissue (5 mg kg-1 per day vs. control ; p

Aging is a physiological process characterized by a reduced ability to respond to environmental stressors. Despite many aging theories, this process is still poorly understood. As evidenced in recent studies, aging may be associated with increased oxidative stress (OS), which may affect an organ’s functional and morphological characteristics. Reactive oxygen species can change the structure and function of membrane lipids, inhibit enzyme activities and oxidative phosphorylation, and oxidize nucleic acids and proteins. This study used gonadectomised rats (N=5) as an experimental model of aging and sham-operated rats as the controls to investigate if sex hormones affect OS parameters in the major internal organs. Experiments were performed on three-month old Wistar rats of both sexes six weeks after the surgical procedures. Glutathione (GSH) was measured in the kidneys, liver, brain and plasma. Significant difference in GSH concentration was observed only in plasma of sham-operated females (3.62±0.34 nmol g-1 tissue) compared to sham-operated males (4.93±0.68 nmol g-1 tissue, mean±SD ; P

Mikotoksini su toksični proizvodi plijesni koji mogu biti karcinogeni, genotoksični, mutageni i teratogeni. Pri umjerenoj klimi najčešće se u hrani za životinje nalaze aflatoksini, trihoteceni, fumonizini, zearalenon i okratoksin A, a sintetiziraju ih najčešće plijesni rodova Aspergillus, Penicillium i Fusarium. Pogodovni čimbenici za nastanak mikotoksina na žitaricama su zaraza toksinogenim plijesnima, ugljikohidratna podloga i učestale vegetacijske godine s izraženijim promjenama temperature i količine oborina. Nastanku mikotoksina na žitaricama u polju pogoduje korištenje hibrida koji daju visoke prinose uz smanjenu otpornost na stres, reducirana osnovna obrada, povećana gustoća sklopa, uzgoj u monokulturi i povećana zakorovljenost. Kontaminiranosti pogoduje mehanizirana žetva s povećanim lomom zrna, vlažnost zrna, naseljavanje štetnika tijekom skladištenja i skladištenje usjeva u velikim skladišnim prostorima što neminovno dovodi do miješanja zdravog i zaraženog usjeva. Hrvatska agencija za hranu provela je opsežno istraživanje s ciljem prikazivanja stanja zaraženosti dominantnih krmiva (sačma soje, kukuruz) koja količinski čine najveći udio u svim krmnim smjesama kako bi se procijenio rizik za životinje, a posljedično i za ljude. Uzorci sačme soje i kukuruza sakupljeni su kod 20 najvećih proizvođača hrane za životinje u Republici Hrvatskoj. Obim i intenzitet zaraženosti aflatoksinom, zearalenonom, deoksinivalenolom i fumonizinom B1 analiziran je na 300 uzoraka (181 kukuruza, 119 sačma soje) iz vegetacijske godine 2011. metodom ELISA (Enzyme-Linked Immunosorbent Assay). U kukuruzu je koncentracija aflatoksina iznad granice detekcije nađena u 23 % uzoraka (raspon 1, 0-10, 0 μg/kg), deoksinivalenola u 25 % (55- 500 μg/kg), fumonizina u 55 % (220-2000 μg/kg), a zearalenon je nađen samo u jednom uzorku. U sačmi soje aflatoksini su nađeni u 16 % uzoraka (raspon 1, 0-2, 0 μg/kg), deoksinivalenol u 30 % (55-200 μg/kg), zearalenon u 29 % (16-100 μg/kg) dok niti jedan uzorak nije bio kontaminiran fumonizinima iznad granice detekcije. Dobiveni rezultati ukazuju na učestalu kontaminaciju mikotoksinima. Koncentracije aflatoksina B1 znatno su niže od maksimalno dozvoljenih koncentracija propisanih Pravilnikom o nepoželjnim tvarima u hrani za životinje (NN 80/2010). I ostali analizirani mikotoksini nađeni su u koncentracijama koje su niže od onih koje je preporučila Europska komisija.

In order to protect European consumers from the exposure of all kinds of possible lesions and diseases of food origin the European Commission (EC) founded the independent scientific advisory board called European Food Safety Authority (EFSA). In 2003, EFSA organized Panel on Contaminants in the Food Chain (CONTAM Panel) with the mandate to deliver scientific opinions on “contaminants in food and feed, associated areas and undesirable substances such as natural toxicants, mycotoxins and residues of non-authorized substances not covered by another Panel”. CONTAM Panel receives the requests from the EC (95 %), Member States (1 %) and the European Parliament (1 %). Since 2003 CONTAM Panel produced 107 opinions (55 on contaminants in food, 43 in feed and 9 combined assessments in food and feed), 15 out of them on mycotoxins. Evaluation of risk assessment of mycotoxins is specific because of their natural origin. Mycotoxins are products of moulds that contaminate food and feed all over the world. Low concentrations of mycotoxins are unavoidable in commodities of plant and animal origin. There are about 400 known mycotoxins, but only some of them are known to be toxic, mutagen or carcinogen in animals and humans. Mycotoxins have rather different chemical structure and their metabolism, which determines their untoward effects in organisms in most cases are not elucidated. They are stable compounds, resistant to heating and food production does not destroy them although in some cases it decreases their concentration. Risk assessment is the procedure of evaluation whether or not a hazardous chemical contaminant or undesirable substance in food is likely to be associated with adverse health effects in the population. Risk assessment is based on two components: the potential of substance to cause adverse effects (hazard) and knowledge about the human exposure to the substance. In the procedure of hazard identification in case of mycotoxins all available data regarding the evaluated compound in the scientific literature are taken into account. These data include reports on the human and animal intoxication, studies on experimental animals as well as on the cell cultures. For the evaluation of human exposure CONTAM Panel relies on data on occurrence of contaminants submitted by Member States upon the calls for data. Risk assessment for animals is based on less reliable feed consumption data and therefore contains more uncertainties.

Ageing is characterized by an impaired functional and structural integrity of mammalian kidneys. A diminished handling of organic compounds, drugs, and water, as observed in the kidneys of older humans and experimental animals, indicates that ageing may affect the expression and/or activity of the renal transporters that mediate excretion and/or reabsorption of organic anions and cations, glucose, and water. We compared the expression of relevant transporters in the kidneys of 3-month- old and 24-month-old male Wistar rats, including Na/K-ATPase, organic anion transporters Oat1 (Slc22a6), Oat2 (Slc22a7), Oat3 (Slc22a8), and Oat5 (Slc22a19), organic cation transporters Oct1 (Slc22a1) and Oct2 (Slc22a2), glucose transporters Sglt1 (Slc5a1) and Sglt2 (Slc5a2), and water channels AQP1 and AQP2. These transporters/channels reside in specific cell membrane domains along the nephron. Protein expression was studied by immunofluorescence cytochemistry (IC) in tissue cryosections and Western blotting (WB) in isolated membranes, whereas expression of mRNA in the tissue was tested by RT-PCR. The protein and mRNA expression of Oat1, Oat3, Oct1, Oct2, and AQP1 was significantly weaker in senescent animals. However, the expression of Na/K-ATPase, Oat2, Oat5, Sglt1, Sglt2, and AQP2 at both protein and/or mRNA levels was not affected by age. Our findings imply that the cellular uptake and excretion of endogenous and/or exogenous compounds in the kidneys can be compromised due to the ageing-related downregulation of certain renal transporters. This can lead to an impaired ability to maintain the homeostasis of specific compounds and an increased susceptibility to drug interaction and toxicity in kidneys and other organs.

Mikotoksini su toksični proizvodi plijesni koji mogu biti karcinogeni, genotoksični, mutageni i teratogeni. Pri umjerenoj klimi najčešće se u hrani za životinje nalaze aflatoksini, trihoteceni, fumonizini, zearalenon i okratoksin A, a sintetiziraju ih najčešće plijesni rodova Aspergillus, Penicillium i Fusarium. Pogodovni čimbenici za nastanak mikotoksina na žitaricama su zaraza toksinogenim plijesnima, ugljikohidratna podloga i učestale vegetacijske godine s izraženijim promjenama temperature i količine oborina. Nastanku mikotoksina na žitaricama u polju pogoduje korištenje hibrida koji daju visoke prinose uz smanjenu otpornost na stres, reducirana osnovna obrada, povećana gustoća sklopa, uzgoj u monokulturi i povećana zakorovljenost. Kontaminiranosti pogoduje mehanizirana žetva s povećanim lomom zrna, vlažnost zrna, naseljavanje štetnika tijekom skladištenja i skladištenje usjeva u velikim skladišnim prostorima što neminovno dovodi do miješanja zdravog i zaraženog usjeva. Hrvatska agencija za hranu provela je opsežno istraživanje s ciljem prikazivanja stanja zaraženosti dominantnih krmiva (sačma soje, kukuruz) koja količinski čine najveći udio u svim krmnim smjesama kako bi se procijenio rizik za životinje, a posljedično i za ljude. Uzorci sačme soje i kukuruza sakupljeni su kod 20 najvećih proizvođača hrane za životinje u Republici Hrvatskoj. Obim i intenzitet zaraženosti aflatoksinom, zearalenonom, deoksinivalenolom i fumonizinom B1 analiziran je na 300 uzoraka (181 kukuruza, 119 sačma soje) iz vegetacijske godine 2011. metodom ELISA (Enzyme-Linked Immunosorbent Assay). U kukuruzu je koncentracija aflatoksina iznad granice detekcije nađena u 23 % uzoraka (raspon 1, 0-10, 0 μg/kg), deoksinivalenola u 25 % (55- 500 μg/kg), fumonizina u 55 % (220-2000 μg/kg), a zearalenon je nađen samo u jednom uzorku. U sačmi soje aflatoksini su nađeni u 16 % uzoraka (raspon 1, 0-2, 0 μg/kg), deoksinivalenol u 30 % (55-200 μg/kg), zearalenon u 29 % (16-100 μg/kg) dok niti jedan uzorak nije bio kontaminiran fumonizinima iznad granice detekcije. Dobiveni rezultati ukazuju na učestalu kontaminaciju mikotoksinima. Koncentracije aflatoksina B1 znatno su niže od maksimalno dozvoljenih koncentracija propisanih Pravilnikom o nepoželjnim tvarima u hrani za životinje (NN 80/2010). I ostali analizirani mikotoksini nađeni su u koncentracijama koje su niže od onih koje je preporučila Europska komisija.

Mycotoxicoses are acute or chronic diseases of humans and animals caused by mycotoxins, toxic compounds produced by moulds. Of about 400 known mycotoxins only a small number are known to cause mycotoxicoses in humans. Organs that are most targeted are those in which mycotoxins are metabolised, that is, the liver and kidneys, but the lesions may affect the neurological, respiratory, digestive, haematological, endocrine, and immune systems as well. The epidemics of mycotoxicoses are often connected with times of famine, when population consumes food that would not be consumed in normal circumstances. Mycotoxicoses have infl uenced human history, causing demographic changes, migrations, or even infl uencing the outcomes of wars. Fortunately, epidemics affecting so many persons and with so many fatalities belong to the past. Today they only appear in small communities such as schools and factory canteens. This paper presents epidemics and pandemics of mycotoxicoses that infl uenced human history.

Toksini plijesni, zvani mikotoksini, često se nalaze u hrani i krmivu u svim krajevima svijeta. Mikotoksini mogu na različite načine štetiti ljudskom zdravlju jer osim bolesti uzrokovanih njihovom toksičnošću koje se u ljudi i životinja nazivaju mikotoksikozama, mogu biti karcinogeni, genotoksični i mutageni. Akutne mikotoksikoze, koje nastaju pri izloženosti ljudi i životinja velikoj koncentraciji mikotoksina, česte su u zemljama s tropskom klimom gdje su povoljniji uvjeti za rast plijesni i sintezu mikotoksina. U zemljama s umjerenom klimom akutne su mikotoksikoze velikih razmjera danas rijetke, iako su u povijesti nekoliko puta poharale stanovništvo Europe. Kronične su mikotoksikoze posljedica dugotrajne izloženosti nekom mikotoksinu i također su češće u tropskim zemljama. Povezanost nastanka bolesti s izloženošću nekom mikotoksinu vrlo je teško dokazati jer su ljudi i životinje izloženi istovremeno različitim mikotoksinima. Ljudi su u umjerenim klimatskim zonama, pa i u Hrvatskoj, često izloženi mikotoksinima fumonizinu B1 (FB1), okratoksinu A (OTA) i zearalenonu (ZEA), dok je izloženost aflatoksinu B1 (AFB1) rjeđa. Na pokusnim je životinjama dokazano da je ciljni organ toksičnog djelovanja za AFB1 jetra, za OTA bubreg, a za ZEA reproduktivni sustav. Vrlo je vjerojatno da su to ciljni organi njihovog djelovanja i kod ljudi. FB1 pokazuje znatnu razliku ciljnog organa kod različitih životinjskih vrsta, pa je teško pretpostaviti koji je njegov ciljni organ u ljudi. Dokazano je da izloženost mikotoksinu AFB1 uzrokuje maligne tumore u ljudi, a prema istraživanjima na pokusnim životinjama pretpostavlja se da bi FB1 i OTA mogli biti karcinogeni i za ljude. U radu su opisani akutni i kronični učinci mikotoksina AFB1, FB1, OTA i ZEA jer se ti mikotoksini mogu naći u hrani i krmivu u Hrvatskoj pa su ljudi trajno izloženi tim mikotoksinima.

Tijekom 2010. nastupile su promjene u organizaciji i rukovodstvu Hrvatskoga toksikološkog društva. U ovome kratkom članku dan je kratki prikaz povijesti Društva te pregled najvažnijih aktivnosti i planova koje ono namjerava provesti u predstojećem razdoblju kako bi se ojačao položaj toksikologije kao znanstvene discipline. [In 2010, the Croatian Toxicological Society reorganised and renewed its executive staff. This article gives a brief review of the Society’s history and the most important activities and plans for the near future that would strengthen the position of toxicology as a research discipline.]

Neither positive correlation between BuChE and triglycerides nor negative correlation between BuChE and HDL was found. Changes in lipid profile during DM treatment were not sex- and time- dependent.

Oksidacijski stres nastaje kada proizvodnja ROS-a nadvlada staničnu zaštitu antioksidansima. Definira se kao pomak ravnoteže u staničnim oksidacijsko-redukcijskim reakcijama u smjeru oksidacije. Riječ je o stanju prekomjernog stvaranja slobodnih radikala kisika koji oštećuju staničnu membranu, razgrađuju višestruko nezasićene masne kiseline, pri čemu nastaju produkti lipidne peroksidacije, oksidiraju neke aminokiseline ili kidaju peptidnu vezu, depolimeriziraju polisaharide i oštećuju DNK. Opća anestezija i kirurško liječenje mogu promijeniti ravnotežu imunosnog i antioksidacijskog sustava, što povećava stopu komplikacija i odgađa oporavak nakon operacije. Važno je znati koji su učinci anestetika na oksidacijski stres, posebno u operacijama s visokom produkcijom ROS-a, jer njihov aditivni ili antagonistički učinak može biti presudan za ishod operacije. Studije in vitro i studije na životinjama na tu temu brojne su, ali pokazuju veliku varijabilnost. Nema puno studija na ljudima, a ono što znamo, temelji se na različitim operacijama i na biljezima oksidacijskog stresa koji su različito mjereni najčešće prije i nakon nje. Dosad većina intravenskih anestetika ima antioksidacijska svojstva, dok inhalacijski anestetici pri duljim operacijama privremeno povećavaju oksidacijski stres. Hipoteza je ovog istraživanja bila da anestezija vođena ciljnom koncentracijom lijeka u djece s hidronefrozom, podvrgnute operaciji po metodi Anderson-Hynes, izražava manji oksidacijski stres u odnosu na balansiranu anesteziju. Cilj je ovog istraživanja bio utvrditi anesteziološku tehniku (balansirana, TCI/TIVA) koja izaziva manji oksidacijski stres u djece s hidronefrozom podvrgnute operaciji po metodi Anderson-Hynes zbog stenoze pijeloureteričnog vrata. Osim toga, specifično je trebalo utvrditi dinamiku kretanja markera oksidacijskog stresa u perioperacijskom razdoblju: prije uvoda u anesteziju, 30 min i 24 h od početka operacije. Prikupljeni su uzorci krvi u 32 ispitanika u dobi od tri do 16 godina u trima navratima u perioperacijskom razdoblju: prije uvoda u anesteziju, 30 min i 24 h od početka operacije. Uzorci krvi pohranjeni su u zamrzivaču na -20 °C te analizirani na kraju istraživanja. Analizirani su MDA, GSH, SOD, ROS, FRAP i proteinski karbonili. Rezultati provedenog istraživanja nisu potvrdili postavljenu hipotezu da anestezija vođena ciljnom koncentracijom lijeka u djece s hidronefrozom, podvrgnute operaciji po metodi Anderson-Hynes, izražava manji oksidacijski stres u odnosu na balansiranu anesteziju. Uspoređujući sve koncentracije biljega oksidacijskog stresa mjerene u ovom istraživanju, one se nisu statistički značajno razlikovale između skupina u odnosu na vrijeme prikupljanja. Originalni rezultati ovog istraživanja omogućit će i dalje korištenje objema anesteziološkim tehnikama kod takve operacije bez dodatna povećavanja oksidacijskog stresa koji ona prouzročuje. Isto tako, rezultati ovog istraživanja proširit će saznanja o utjecaju balansirane anestezije i anestezije vođene ciljnom koncentracijom lijeka na veličinu oksidacijskog stresa u djece., Oxidative stress occurs when reactive oxygen species (ROS) production overwhelms the cell protection by antioxidants. This condition could damage the cell membrane, decompose polyunsaturated fatty acids, creating products of lipid peroxidation, cause oxidation of an amino acid, depolymerized polysaccharides and damage DNA. It is important to know what effects of anesthetics to expect in terms of oxidative stress, particularly in surgical procedures with high ROS production, because their either additive or antagonistic effect may be pivotal for the outcome of surgery. In vitro and animal studies on this topic are numerous, but show large variability. There are not many human studies and the best of our knowledge has been learned from different surgical procedures measuring different endpoints in blood samples taken mostly before and after surgery. Usually intravenous anesthetics have antioxidative properties, while volatile anesthetics temporarily increase oxidative stress in longer surgical procedures. This research is to determine the magnitude of oxidative stress between balanced anesthesia and anesthesia with Target Controlled Infusion in children subjected to Anderson-Hynes operation. Oxidative sress induced by general anesthesia is an important factor in causing higher rate of postoperative complications and delayed recovery after surgery.

Okratoksin A (OTA) i citrinin (CTN) su nefrotoksični mikotoksini koji se često zajedno nalaze u žitaricama. Mehanizam djelovanja OTA nije do kraja istražen, a CTN-a je gotovo u potpunosti nepoznat. Zbog zajedničkog pojavljivanja i pretpostavke da je u mehanizam njihove toksičnosti uključen oksidacijski stres provedena su istraživanja na muškim odraslim Wistar štakorima koji su danomice oralno tretirani s OTA (125 i 250 μg kg-1 tm x21), CTN-om (20 mg kg-1 tmx2) i resveratrolom (20 mg kg-1 tmx21). Ciljevi istraživanja bili su utvrditi: izaziva li tretman CTN-om oksidacijski stres, utječe li tretman s OTA i CTN-om na povećanje oksidacijskog stresa u pokusnim životinjima te može li tretman antioksidacijskim spojem resveratrolom smanjiti nastanak oksidacijskog stresa izazvanog djelovanjem OTA i CTN. CTN je uzrokovao smanjenje koncentracije glutationa (GSH) u plazmi i povećanje intenziteta repa kometa u bubregu. Nađeno je da CTN pojačava učinak OTA povećanjem koncentracije MDA u plazmi i jetri, a posebice u bubregu gdje se taj učinak smanjuje tretmanom resveratrolom. Zajedničkim tretmanom s OTA i CTN-om snižava se koncentracija GSH u jetri nakon niže koncentracije OTA, a u bubregu i mozgu nakon više. Učinak dodatnog tretmana s resveratrolom jest značajno niža koncentracija GSH nađena samo u bubregu. Budući da je snižena koncentracija GSH primijećena u bubregu i mozgu pri većoj koncentraciji OTA, učinak na sniženje koncentracije GSH može se pripisati tom mikotoksinu. Učinak tretmana s OTA i CTN-om nije bio jednoznačan na djelovanje antioksidacijskih enzima. Katalaza je bila najmanje osjetljiva na djelovanje mikotoksina, a superoksid dismutaza najosjetljivija. Oštećenje DNA mjereno kometskim testom bilo je izraženo kada su životinje tretirane s oba mikotoksina a intenzitet repa bio je osjetljiviji parametar oštećenja. Primjena resveratrola nije spriječila oksidacijsko oštećenje DNA. Ochratoxin A (OTA) and Citrinin (CTN) are nephrotoxic mycotoxins commonly found together in grain. The toxicity mechanism of OTA has not been fully explained, while the toxicity mechanism of CTN is all but unknown. Because they commonly appear together in nature and because it is hypothesized that oxidative stress is somehow included in their toxicity mechanisms, a research was performed on adult male Wistar rats which were treated daily with OTA (125 i 250 μg kg-1 bm x21), CTN (20 mg kg-1 bmx2) and resveratrol (20 mg kg-1 bmx21). The goals of the research were to establish whether CTN treatment induces oxidative stress, whether combined OTA and CTN treatment increases oxidative stress in tested animals and whether treatment with the antioxidant compound resveratrol can reduce the levels of oxidative stress induced by OTA and CTN. CTN treatment caused a reduction in glutathione (GSH) concentration levels in plasma samples and an increase of comet tail length in kidney samples. It has been established that CTN augments the effects of OTA by increasing malondialdehyde (MDA) concentration levels in plasma and liver tissue and especially in the kidneys where this effect is reduced by resveratrol treatment. GSH concentration levels are decreased in liver samples after treatment with both dosages of OTA, while kidney and brain samples display this reduction only after treatment with the higher dosage. The effect of resveratrol treatment is that a significant reduction in GSH concentration levels is found only in kidney samples. Since GSH concentration reduction was observed in all experiments with higher OTA dosages, the effect can be attributed to that mycotoxin. The effect of the combined OTA and CTN treatment on oxidative enzyme levels is ambiguous. Catalase activity was least sensitive to the effect of mycotoxins, while superoxide dismutase activity was most sensitive. DNA damage measured with the comet assay was prominent in animals treated with both mycotoxins with tail intensity being the better damage indicator. Treatment with resveratrol did not prevent DNA oxidative damage.