Biosynthesis and Toxicological Effects of Patulin

Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects

Allopurinol Reduces the Lethality Associated with Acute Renal Failure Induced by Crotalus durissus terrificus Snake Venom: Comparison with Probenecid

In Brazil, among registered snake bites, those by the genus Crotalus originate the highest mortality rate. The rattlesnake Crotalus durissus terrificus is the most frequently implicated in these accidents. The kidney is a particularly vulnerable organ to the venom of this rattlesnake. In fact, the most serious complication of Crotalus snake bite is the renal dysfunction, and among the fatal cases of Crotalus bites in Brazil 5% are patients treated with antivenom. The hyperuricemia has been observed in human accidents with snake venoms, but this parameter has not received any special attention as a relevant factor in the etiology of renal dysfunction caused by these venoms. This study examined the effects of treatments with low-cost and low-risk uricostatic (allopurinol) and uricosuric (probenecid) drugs on the envenomation by C. d. terrificus, showing that allopurinol and probenecid mitigated certain nephrotoxic effects, as well as the survival of envenomed mice was improved through the effects of allopurinol on reduction of oxidative stress and intracellular formation of uric acid. This new knowledge provides consistent evidences linking uric acid with the renal dysfunction induced by rattlesnake bites and that the allopurinol deserves to be clinically evaluated as an approach complementary to anti-snake venom serotherapy

Risks for public health related to the presence of furan and methylfurans in food

EFSA wishes to thank the hearing experts: Diana Doell and Ruud Woutersen and EFSA staff member: José Cortinas Abrahantes for the support provided to this scientific output. The CONTAM Panel acknowledges all European competent institutions and other stakeholders that provided occurrence data on furan and methylfurans in food, and supported the data collection for the Comprehensive European Food Consumption Database. Adopted: 20 September 2017Peer reviewedPublisher PD

Comparison Of Phototoxic Effects Of Hypericin-Mediated Photodynamic Therapy In Ht-29 And Caco-2 Colon Cancer Cells

Hypericin (HYP) is a plant-derived photosensitizer. HYP is preferentially taken up by tumor cells. We designed this study to compare HYP-mediated photodynamic therapy (PDT) in HT-29 and Caco-2 colon cell lines. Cells were treated with 0.04, 0.08, and 0.15 mu M HYP concentrations and irradiated. The effect of HYP on metabolic profiles, alterations in lactate dehydrogenase (LDH) leakage, and cell cycle progression was investigated for the first time. Changes in glucose consumption, lactate production, and LDH leakage were analyzed. HYP-induced cell death was quantified by double staining (acridine orange/propidium iodide) and alterations in cell cycle regulation were analyzed with flow cytometry (using propidium iodide). LDH leakage and the number of dead cells were elevated, and glucose consumption and lactate production decreased in a dose-and time-dependent manner. PDT resulted in an induction of apoptosis, mostly at the 0.08 mu M HYP concentration. Apoptosis and/or necrosis were increased in the 0.15 mu M HYP group. The accumulation of cells in the G2/M phase might account for the growth inhibition in HT-29 and Caco-2 cells with 0.08 mu M HYP photoactivation. The observed G2/M arrest suggested that HYP may slow down the growth of colon cancer cells by regulating the cell cycle, leading either to growth inhibition or to initiation of apoptotic pathways.WoSScopu

Efekat polena na neke reproduktivne parametre mužjaka pacova

Honeybee pollen is consumed as natural food in healthy human diet in many European and Asian countries. The aim of this study was to investigate the effect of pollen use on some reproductive parameters. In this study, mature male rats were fed on pollen of three different plant sources (Trifolium spp., Raphanus spp. and Cistus spp.) at 60 mg/per animal/ per day over a 30-day period. At the end of the treatment, testosterone levels of rats were analysed and weights of testis, epididymis, prostate and seminal vesicle were recorded. In addition, epididymal sperms were counted. There were increases in testosterone levels, sperm counts and daily sperm production of rats fed with pollen of Raphanus spp. and Cistus spp. There were no significant changes in absolute weights, except in prostate weights. Also there were no changes in relative testis, prostate and seminal vesicle weights of rats fed on pollen, but relative epididymis weights of rats in pollen groups decreased. The results of this study show that bee pollen caused an increase in testosterone level and sperm counts of male rats. We suggest that bee pollen has an androgenic effect.Pčelinji polen kao prirodna hrana predstavlja deo zdrave ishrane u mnogim evropskim i azijskim zemljama. Cilj ovog istraživanja je bio da se ispita delovanje polena na neke reproduktivne parametre. Mužjaci pacova su hranjeni polenom dobijenim iz tri različita biljna izvora (Trifolium spp., Raphanus spp. i Cistus spp.) i to u dnevnim dozama od 60 mg po životinji tokom perioda od 30 dana. Na kraju tretmana, analiziran je nivo testosterona i merena težina testisa, epididimisa i semenih kesica pacova. Pored toga, merena je brojnost epididimalnih spermatozoida. Zabeležen je porast nivoa testosterona, brojnosti spermatozoida i dnevne produkcije sperme kod pacova hranjenih polenom Raphanus spp. i Cistus spp. Nije bilo značajnih promena apsolutne težine, osim težine prostate. Takođe, nije bilo promene relativne težine testisa, prostate i semenih kesica kod pacova hranjenih polenom, ali je smanjena relativna težina epididimisa pacova u grupama koje su dobijale polen. Rezultati ovog istraživanja pokazuju da je pčelinji polen doveo do povećanja nivoa testosterona i brojnosti spermatozoida kod mužjaka pacova. Po našem mišljenju, pčelinji polen ima androgeno delovanje

In Vivo Toxicity Of A New Antifungal Agent 2,4-Dithiophenoxy-1-Iodo-4-Bromo Benzene: A Follow Up On Our In Vitro Study

Triazole fungicide fluconazole has become the most widely used antifungal agent in the world, mainly because of its ability to penetrate well into body fluids and tissues. However, it has been reported to interact with many drugs and because of its common use, the risk of resistance to fluconazole increases. This calls for new anti-fungal drugs that would be able to replace it. In 2006, a new thialo benzene derivative -2,4-dithiophenoxy-1-iodo-4-bromo benzene (C18H12S2IBr) - was synthesised with a carbon backbone similar to fluconazole, and, according to the early in vitro tests, much greater efficiency. Followed an in vitro test of its cytotoxicity, in which the new drug showed promising results as an alternative to fluconazole. The aim of this study was take the next step and test C18H12S2IBr toxicity in vivo. We opted for a four-week test on Wistar rats, in which the new antifungal agent was orally applied at doses two and a half and five times lower than those of fluconazole. There were no changes in daily food and water consumption, but weight gain in female rats and relative organ weights changed in the treated groups, pointing to sex-related differences in drug metabolism and effects. Fluconazole significantly increased leukocytes and lowered neutrophils whereas C18H12S2IBr did not, while other haematological changes in respect to the vehicle control were similar between the treated groups. Differences in cytochrome c in the liver and kidney suggested greater apoptotic effect of the new drug, but interpretation remains inconclusive, considering that other key indicators (biochemistry and histopathology) do not support greater toxicity. Considering that C18H12S2IBr is more active at lower concentrations and has comparable toxic effects to fluconazole in rats, this new compound shows some promise in the treatment of fungal infections. Future, more detailed animal studies are needed, that will include drug interactions and molecular toxicity pathways. If the results are promising, clinical studies should follow.WoSScopu

Evaluation of isoindole derivatives: Antioxidant potential and cytotoxicity in the HT‐29 colon cancer cells

Suloglu, Aysun Kilic/0000-0003-0914-1128Norcantharimides have an isoindole skeleton structure, and some isoindoline derivatives have positive effects on inflammatory pathologies, including cancers. The present study aims to evaluate the antioxidant and cytotoxic potential of four synthesized isoindoline derivatives (NCTD1-4). HT-29 cells exposed to 10, 50, 100, and 200 mu M doses of each derivative were incubated for 24 and 48 h, respectively. The cytotoxicity of the new derivatives was analyzed using the cell growth inhibition assay and the cell membrane damage test. In vitro antioxidant activity studies showed that the derivatives have free radical-scavenging effects in a dose-dependent manner. NCTD3 and NCTD4 apparently have antioxidant effects when compared with the control group treated with dimethyl sulfoxide. Furthermore, NCTD4 inhibited the growth of the HT-29 cells due to membrane damage and exhibited a dose-dependent cytotoxic effect on colon adenocarcinoma cells. The findings suggest that NDTD4 has the highest potential for colon cancer treatment and may be interpreted as a candidate anticancer agent.Hacettepe University Scientific Research Project UnitHacettepe University [014 D07 301 002-664]This study was supported by Hacettepe University Scientific Research Project Unit (Project Number: 014 D07 301 002-664)