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Rui Gil M Da Costa - One of the best experts on this subject based on the ideXlab platform.

  • Ptaquiloside from bracken pteridium spp promotes oral carcinogenesis initiated by hpv16 in transgenic mice
    Food & Function, 2020
    Co-Authors: Rui Gil M Da Costa, Carlos Lopes, Tiago Neto, Rui Medeiros, Diogo Estevao, Magda S S Moutinho, Ana Felix, Margarida M S M Bastos
    Abstract:

    Bracken (Pteridium spp.) is a common weed that is consumed as food especially in Asia, and is suspected of promoting carcinogenesis induced by papillomaviruses in the digestive and urinary systems. This is particularly worrying because the incidence of head-and-neck cancers associated with the human papillomavirus (HPV) is rapidly increasing, and HPV co-carcinogens urgently need to be identified. This study tested the hypothesis that two bracken compounds, Ptaquiloside and rutin, are able to promote head-and-neck and bladder carcinogenesis in HPV16-transgenic mice. Expression of HPV16 E6 and E7 in oral and bladder tissues was confirmed using quantitative real-time PCR. Mice were exposed orally to Ptaquiloside (0.5 mg per animal per week for 10 weeks from 20 weeks-old) or rutin (413 mg kg-1 day-1 for 24 weeks from 6 weeks-old), sacrificed at 30 weeks-old and studied histologically. HPV16 E6 and E7 expression was higher in oral mucosa compared with the bladder (p 0.001). Importantly, Ptaquiloside, but not rutin, increased the incidence of oral squamous cell carcinomas (p = 1.2 × 10-8) in HPV16-transgenic mice. Also, cancers of unexposed transgenic mice were restricted to the tongue base, while Ptaquiloside-exposed mice showed multifocal lesions throughout the oral cavity. Wild-type controls showed no oral lesions. No bladder lesions were observed in any treated or untreated group. These results indicate that Ptaquiloside from bracken is able to promote oral carcinogenesis initiated by HPV16. Rutin did not show any carcinogenic effects in this model. The absence of bladder lesions may reflect an insufficient incubation period or factors related to the specific viral oncogenes present in this model.

  • Ptaquiloside from bracken pteridium spp inhibits tumour infiltrating cd8 t cells in hpv 16 transgenic mice
    Food and Chemical Toxicology, 2016
    Co-Authors: Carlos Santos, Paula A Oliveira, Margarida M S M Bastos, Pedro Ferreirinha, Hugo Sousa, Joana Ribeiro, Tiago Neto, Rui Medeiros, Manuel Vilanova, Rui Gil M Da Costa
    Abstract:

    Abstract Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as Ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of Ptaquiloside on tumour-infiltrating CD8+ T lymphocytes, which are critical players in anti-tumour immunity. HPV16+/− mice received Ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8+ T cells analysed for CD107a and CD44 surface expression. Ptaquiloside-exposed HPV16+/− mice showed a significantly decreased percentage (P

  • Ptaquiloside from bracken (Pteridium spp.) inhibits tumour-infiltrating CD8(+) T cells in HPV-16 transgenic mice
    'Elsevier BV', 2016
    Co-Authors: Carlos Santos, Paula A Oliveira, Margarida M S M Bastos, Pedro Ferreirinha, Hugo Sousa, Joana Ribeiro, Tiago Neto, Rui Medeiros, Manuel Vilanova, Rui Gil M Da Costa
    Abstract:

    Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as Ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of Ptaquiloside on tumour-infiltrating CD8(+) T lymphocytes, which are critical players in anti-tumour immunity. HPV16(+/-) mice received Ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8(+) T cells analysed for CD107a and CD44 surface expression. Ptaquilosideexposed HPV16(+/-) mice showed a significantly decreased percentage (P < 0.05) of CD8(+)CD107(+) and CD8(+)CD44 T cells when compared with untreated HPV16(+/)- animals. Histologically, 100% of ptaqui-losidetreated mice showed diffuse epidermal dysplasia, compared with 50% of the untreated mice. These findings suggest that Ptaquiloside exerts an immunosuppressive role by decreasing CD8(+) T cell activation and degranulation in HPV-induced lesions. Given the key role of CD8(+) T lymphocytes against HPV-induced lesions, this effect is likely to contribute for viral persistence, tumour progression and increased aggressiveness in patients with HPV-related malignancies

  • Ptaquiloside induced early stage urothelial lesions show increased cell proliferation and intact β catenin and e cadherin expression
    Environmental Toxicology, 2014
    Co-Authors: Rui Gil M Da Costa, Paula A Oliveira, Margarida M S M Bastos, Celia Lopes, Carlos Lopes
    Abstract:

    Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin, Ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside contaminates underground waters as well as meat and milk from bracken-grazing animals and is a suspected human carcinogen. A better understanding of the underlying mechanisms of carcinogenesis can be achieved by studying the early stages of this process. Unfortunately, most research on Ptaquiloside has focused on the late, malignant, lesions, so the early changes of Ptaquiloside-induced carcinogenesis remain largely unknown. This study aims to characterize early-stage Ptaquiloside-induced urinary bladder lesions both morphologically and immunohistochemically. 12 male CD-1 mice were administered 0.5 mg Ptaquiloside intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment. 12 control animals were administered saline. Bladders were tested immunohistochemically for antibodies against a cell proliferation marker (Ki-67), and two cell adhesion markers (E-cadherin and β-catenin). Two exposed animals died during the work. Six Ptaquiloside-exposed mice developed low-grade and two developed high grade urothelial dysplasia. No lesions were detected on control animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on dysplastic urothelium from Ptaquiloside-exposed mice, compared with controls. No differences were found concerning E-cadherin and β-catenin expression. Early-stage Ptaquiloside-induced urothelial lesions show increased cell proliferation but there is no evidence for reduced intercellular adhesiveness, though this may be a later event in tumor progression. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 763–769, 2014.

  • Ptaquiloside-induced early-stage urothelial lesions show increased cell proliferation and intact ß-catenin and e-cadherin expression
    'Wiley', 2014
    Co-Authors: Rui Gil M Da Costa, Paula A Oliveira, Margarida M S M Bastos, Bastos Mmsm, Célia C. Lopes
    Abstract:

    Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin, Ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside contaminates underground waters as well as meat and milk from bracken-grazing animals and is a suspected human carcinogen. A better understanding of the underlying mechanisms of carcinogenesis can be achieved by studying the early stages of this process. Unfortunately, most research on Ptaquiloside has focused on the late, malignant, lesions, so the early changes of Ptaquiloside-induced carcinogenesis remain largely unknown. This study aims to characterize early-stage Ptaquiloside-induced urinary bladder lesions both morphologically and immunohistochemically. 12 male CD-1 mice were administered 0.5 mg Ptaquiloside intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment. 12 control animals were administered saline. Bladders were tested immunohistochemically for antibodies against a cell proliferation marker (Ki-67), and two cell adhesion markers (E-cadherin and ß-catenin). Two exposed animals died during the work. Six Ptaquiloside-exposed mice developed low-grade and two developed high grade urothelial dysplasia. No lesions were detected on control animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on dysplastic urothelium from Ptaquiloside-exposed mice, compared with controls. No differences were found concerning E-cadherin and ß-catenin expression. Early-stage Ptaquiloside-induced urothelial lesions show increased cell proliferation but there is no evidence for reduced intercellular adhesiveness, though this may be a later event in tumor progression. © 2012 Wiley Periodicals, Inc

Margarida M S M Bastos - One of the best experts on this subject based on the ideXlab platform.

  • Ptaquiloside from bracken pteridium spp promotes oral carcinogenesis initiated by hpv16 in transgenic mice
    Food & Function, 2020
    Co-Authors: Rui Gil M Da Costa, Carlos Lopes, Tiago Neto, Rui Medeiros, Diogo Estevao, Magda S S Moutinho, Ana Felix, Margarida M S M Bastos
    Abstract:

    Bracken (Pteridium spp.) is a common weed that is consumed as food especially in Asia, and is suspected of promoting carcinogenesis induced by papillomaviruses in the digestive and urinary systems. This is particularly worrying because the incidence of head-and-neck cancers associated with the human papillomavirus (HPV) is rapidly increasing, and HPV co-carcinogens urgently need to be identified. This study tested the hypothesis that two bracken compounds, Ptaquiloside and rutin, are able to promote head-and-neck and bladder carcinogenesis in HPV16-transgenic mice. Expression of HPV16 E6 and E7 in oral and bladder tissues was confirmed using quantitative real-time PCR. Mice were exposed orally to Ptaquiloside (0.5 mg per animal per week for 10 weeks from 20 weeks-old) or rutin (413 mg kg-1 day-1 for 24 weeks from 6 weeks-old), sacrificed at 30 weeks-old and studied histologically. HPV16 E6 and E7 expression was higher in oral mucosa compared with the bladder (p 0.001). Importantly, Ptaquiloside, but not rutin, increased the incidence of oral squamous cell carcinomas (p = 1.2 × 10-8) in HPV16-transgenic mice. Also, cancers of unexposed transgenic mice were restricted to the tongue base, while Ptaquiloside-exposed mice showed multifocal lesions throughout the oral cavity. Wild-type controls showed no oral lesions. No bladder lesions were observed in any treated or untreated group. These results indicate that Ptaquiloside from bracken is able to promote oral carcinogenesis initiated by HPV16. Rutin did not show any carcinogenic effects in this model. The absence of bladder lesions may reflect an insufficient incubation period or factors related to the specific viral oncogenes present in this model.

  • Ptaquiloside from bracken pteridium spp inhibits tumour infiltrating cd8 t cells in hpv 16 transgenic mice
    Food and Chemical Toxicology, 2016
    Co-Authors: Carlos Santos, Paula A Oliveira, Margarida M S M Bastos, Pedro Ferreirinha, Hugo Sousa, Joana Ribeiro, Tiago Neto, Rui Medeiros, Manuel Vilanova, Rui Gil M Da Costa
    Abstract:

    Abstract Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as Ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of Ptaquiloside on tumour-infiltrating CD8+ T lymphocytes, which are critical players in anti-tumour immunity. HPV16+/− mice received Ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8+ T cells analysed for CD107a and CD44 surface expression. Ptaquiloside-exposed HPV16+/− mice showed a significantly decreased percentage (P

  • Ptaquiloside from bracken (Pteridium spp.) inhibits tumour-infiltrating CD8(+) T cells in HPV-16 transgenic mice
    'Elsevier BV', 2016
    Co-Authors: Carlos Santos, Paula A Oliveira, Margarida M S M Bastos, Pedro Ferreirinha, Hugo Sousa, Joana Ribeiro, Tiago Neto, Rui Medeiros, Manuel Vilanova, Rui Gil M Da Costa
    Abstract:

    Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as Ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of Ptaquiloside on tumour-infiltrating CD8(+) T lymphocytes, which are critical players in anti-tumour immunity. HPV16(+/-) mice received Ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8(+) T cells analysed for CD107a and CD44 surface expression. Ptaquilosideexposed HPV16(+/-) mice showed a significantly decreased percentage (P < 0.05) of CD8(+)CD107(+) and CD8(+)CD44 T cells when compared with untreated HPV16(+/)- animals. Histologically, 100% of ptaqui-losidetreated mice showed diffuse epidermal dysplasia, compared with 50% of the untreated mice. These findings suggest that Ptaquiloside exerts an immunosuppressive role by decreasing CD8(+) T cell activation and degranulation in HPV-induced lesions. Given the key role of CD8(+) T lymphocytes against HPV-induced lesions, this effect is likely to contribute for viral persistence, tumour progression and increased aggressiveness in patients with HPV-related malignancies

  • Ptaquiloside induced early stage urothelial lesions show increased cell proliferation and intact β catenin and e cadherin expression
    Environmental Toxicology, 2014
    Co-Authors: Rui Gil M Da Costa, Paula A Oliveira, Margarida M S M Bastos, Celia Lopes, Carlos Lopes
    Abstract:

    Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin, Ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside contaminates underground waters as well as meat and milk from bracken-grazing animals and is a suspected human carcinogen. A better understanding of the underlying mechanisms of carcinogenesis can be achieved by studying the early stages of this process. Unfortunately, most research on Ptaquiloside has focused on the late, malignant, lesions, so the early changes of Ptaquiloside-induced carcinogenesis remain largely unknown. This study aims to characterize early-stage Ptaquiloside-induced urinary bladder lesions both morphologically and immunohistochemically. 12 male CD-1 mice were administered 0.5 mg Ptaquiloside intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment. 12 control animals were administered saline. Bladders were tested immunohistochemically for antibodies against a cell proliferation marker (Ki-67), and two cell adhesion markers (E-cadherin and β-catenin). Two exposed animals died during the work. Six Ptaquiloside-exposed mice developed low-grade and two developed high grade urothelial dysplasia. No lesions were detected on control animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on dysplastic urothelium from Ptaquiloside-exposed mice, compared with controls. No differences were found concerning E-cadherin and β-catenin expression. Early-stage Ptaquiloside-induced urothelial lesions show increased cell proliferation but there is no evidence for reduced intercellular adhesiveness, though this may be a later event in tumor progression. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 763–769, 2014.

  • Ptaquiloside-induced early-stage urothelial lesions show increased cell proliferation and intact ß-catenin and e-cadherin expression
    'Wiley', 2014
    Co-Authors: Rui Gil M Da Costa, Paula A Oliveira, Margarida M S M Bastos, Bastos Mmsm, Célia C. Lopes
    Abstract:

    Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin, Ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside contaminates underground waters as well as meat and milk from bracken-grazing animals and is a suspected human carcinogen. A better understanding of the underlying mechanisms of carcinogenesis can be achieved by studying the early stages of this process. Unfortunately, most research on Ptaquiloside has focused on the late, malignant, lesions, so the early changes of Ptaquiloside-induced carcinogenesis remain largely unknown. This study aims to characterize early-stage Ptaquiloside-induced urinary bladder lesions both morphologically and immunohistochemically. 12 male CD-1 mice were administered 0.5 mg Ptaquiloside intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment. 12 control animals were administered saline. Bladders were tested immunohistochemically for antibodies against a cell proliferation marker (Ki-67), and two cell adhesion markers (E-cadherin and ß-catenin). Two exposed animals died during the work. Six Ptaquiloside-exposed mice developed low-grade and two developed high grade urothelial dysplasia. No lesions were detected on control animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on dysplastic urothelium from Ptaquiloside-exposed mice, compared with controls. No differences were found concerning E-cadherin and ß-catenin expression. Early-stage Ptaquiloside-induced urothelial lesions show increased cell proliferation but there is no evidence for reduced intercellular adhesiveness, though this may be a later event in tumor progression. © 2012 Wiley Periodicals, Inc

Miguel E Alonsoamelot - One of the best experts on this subject based on the ideXlab platform.

  • influence of bracken fern pteridium caudatum l maxon pre treatment on extraction yield of illudane glycosides and pterosins
    Phytochemical Analysis, 2013
    Co-Authors: Yamile C Cacerespena, Marlene Naya, Maria Pia Calcagnopissarelli, Miguel E Alonsoamelot
    Abstract:

    Introduction Bracken (Pteridium spp) illudane glycosidess are labile biologically active terpenoids that undergo decomposition in mild alkali or acid, heat and enzymatic reactions. Hypothetically, quantitation of these weakly chromophoric carcinogens may be challenged by plant sample preparation procedures that may alter the yield of isolates. Objective To study the influence of common plant sample pre-treatments on the recovery of Pteridium caudatum illudane glycoside carcinogens, Ptaquiloside (1a), caudatoside (1c) and Ptaquiloside Z (1d), and associated pterosins A, B and Z (2a, b, c) using HPLC–DAD. Method Bracken fronds were divided in equal left/right sections. One section was subjected to high vacuum desiccation (VD) and the other to freeze-drying (FD), air drying at room temperature (AD) for 7 days, air drying at 70 °C for 72 h (HD), or no treatment (fresh frond, FF). Quantitation was achieved by brief hot-water extraction, base-acid transformation of 1a, 1c and 1d to 2a, b, c and HPLC–DAD analysis against standards. Results Substantial differences in extraction yields were found for all illudane glycosides in the order FF > FD ≈ VD > AD > HD. Illudane instability to HD was 1c > 1d > 1a. Significant losses also were recorded in yields of Pterosins A, B and Z. Conclusion Glycoside extraction suffers from substantial yield loss of all illudane glycosides and indigenous pterosins in all sample pre-treatments studied relative to fresh frond material. Copyright © 2012 John Wiley & Sons, Ltd.

  • Ptaquiloside z a new toxic unstable sesquiterpene glucoside from the neotropical bracken fern pteridium aquilinum var caudatum
    Bioorganic & Medicinal Chemistry, 1998
    Co-Authors: Uvidelio Francisco Castillo, Miguel E Alonsoamelot, Makoto Ojika, Youji Sakagami
    Abstract:

    Abstract Reversed-phase HPLC fractionation, monitored by brine shrimp bioassay, led to the isolation of a new illudane-type sesquiterpene glucoside, Ptaquiloside Z (2), as well as the known bracken carcinogen Ptaquiloside (1), from a bioactive aqueous extract of the neotropical bracken fern Pteridium aquilinum var. caudatum (Pteridaceae). The structure of Ptaquiloside Z (2) was confirmed by spectroscopic analyses and chemical degradation. Both compounds exhibited similar toxicity (LC50 62.5 μg/ml at 24 h and LC50 7.8 μg/ml at 48 h) toward brine shrimp.

  • excretion through milk of Ptaquiloside in bracken fed cows a quantitative assessment
    Lait, 1998
    Co-Authors: Miguel E Alonsoamelot, Barry L Smith, Uvidelio F Castillo, Denis R. Lauren
    Abstract:

    The content of Ptaquiloside (ptaq), a major Pteridium aquilinum carcinogen found in milk from cows fed bracken in Venezuela, has been estimated quantitatively in ils passage through bovines into milk. Six cows were given 6 kg/animal/d of fresh bracken fronds whose ptaq content was deter- mined. Ptaq first appeared in milk 38 h after initially feeding this plant to the cows and continued to be excreted at a relatively constant level, after an induction period, for 62-70 h after the bracken diet had ceased. The average value of total ptaq excreted ((ptaq)e) from milk amounted to 8.60 ± 1.16 % of the total ptaq ingested ((ptaq)) during the entire feeding period. (ptaq)e was linearly dose depen- dent in the 2 400 to 10 000 mg/animal/d range of ptaq given to the test animais and the ratio (ptaqle/jptaq), remained relatively constant at various ptaq dosages. In a two-pulse feeding sequence with a 72-h interlude when no bracken was given, a bimodal ptaq excretion curve was obtained. The implications to human health are discussed. © InralElsevier, Paris

  • isoPtaquiloside and caudatoside illudane type sesquiterpene glucosides from pteridium aquilinum var caudatum
    ChemInform, 1997
    Co-Authors: Uvidelio F Castillo, Alistair L Wilkins, D R Lauren, Barry L Smith, N R Towers, Miguel E Alonsoamelot, Ramon Jaimesespinoza
    Abstract:

    Ptaquiloside and two new illudane-type sesquiterpene glycosides were isolated from Pteridium aquilinum var. caudatum. One- and two-dimensional NMR analyses revealed the new glucosides to be isoPtaquiloside and caudatoside. Four pterosins, A, B, K and Z, were also isolated from a base-acid treated extract.

  • comparative dynamics of Ptaquiloside and pterosin b in the two varieties caudatum and arachnoideum of neotropical bracken fern pteridium aquilinum l kuhn
    Biochemical Systematics and Ecology, 1995
    Co-Authors: Miguel E Alonsoamelot, Serbia M A Rodulfobaechler, Ramon Jaimesespinoza
    Abstract:

    Abstract Significant chemical differences have been observed among the two neotropical varieties of bracken, caudatum and arachnoideum . Trans - o -hydroxycinnamic acid and coumarin have been found only in the caudatum variety. The concentration changes of Ptaquiloside and pterosin B with blade growth were markedly different in caudatum and arachnoideum . In the newly emerged croziers where the concentration of these compounds was highest the former exhibited from 1.98 to 3.9 mg of Ptaquiloside per gram of biomass (mg/gbm) while arachnoideum possessed only between 0.032 and 0.66 mg/gbm. These concentrations decreased consistently with the unfurling of the blade. Pterosin B was found in approximately one-tenth of the Ptaquiloside concentration in most stages, suggesting that these compounds are chemically related in vivo. Caudatum , in retaining a much higher concentration of these toxins than arachnoideum in the full grown frond poses a higher risk of exposure to farm grazing animals that the latter, where Ptaquiloside and pterosin B are almost absent.

Silvana Lima Gorniak - One of the best experts on this subject based on the ideXlab platform.

  • immunosuppressive effects of pteridium aquilinum enhance susceptibility to urethane induced lung carcinogenesis
    Journal of Immunotoxicology, 2015
    Co-Authors: B D Caniceiro, Andreia Oliveira Latorre, Mitsue Haraguchi, Daniel Soares Sanches, Heidge Fukumasu, Silvana Lima Gorniak
    Abstract:

    AbstractPteridium aquilinum (bracken fern), one of the most important toxic plants in the world, contains the toxic norsequiterpene Ptaquiloside that induces cancers in humans and farm animals. Previous studies in the laboratory demonstrated immunotoxic effects produced by Ptaquiloside, which are characterized by suppression of natural killer (NK) cell activity (i.e. cytotoxicity and interferon [IFN]-γ production). However, it is unknown whether these immunosuppressive effects could contribute to carcinogenesis in situ in general because of the important function of NK cells in innate killing of tumor cells. This study assessed the impact of P. aquilinum-induced immunosuppression on urethane-induced lung cancer in C57BL/6 mice. Adult mice were treated with an extract of P. aquilinum (30 g/kg/day) by gavage once daily for 14 days, followed by gavage (5 days/week) during an 11-week period that was accompanied by treatment with urethane (1 g/kg) via once-weekly intraperitoneal injection; 20 weeks after the e...

  • Ptaquiloside reduces nk cell activities by enhancing metallothionein expression which is prevented by selenium
    Toxicology, 2013
    Co-Authors: Andreia Oliveira Latorre, B D Caniceiro, Mitsue Haraguchi, Dale R Gardner, Harry L Wysochi, Heidge Fukumasu, Fabricio Martins Lopes, Tereza Cristina Da Silva, Fabiana Fernandes Bressan, Silvana Lima Gorniak
    Abstract:

    Abstract Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans. Moreover, our previous studies showed that the immunosuppressive effects of Ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cells. We also verified that this immunosuppression facilitated development of cancer. Here, we performed gene expression microarray analysis in splenic NK cells from mice treated for 14 days with Ptaquiloside (5.3 mg/kg) and/or selenium (1.3 mg/kg) to identify gene transcripts altered by Ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium. Transcriptome analysis of Ptaquiloside samples revealed that 872 transcripts were expressed differentially (fold change > 2 and p

  • selenium reverses pteridium aquilinum induced immunotoxic effects
    Food and Chemical Toxicology, 2011
    Co-Authors: Andreia Oliveira Latorre, B D Caniceiro, H L Wysocki, Mitsue Haraguchi, Dale R Gardner, Silvana Lima Gorniak
    Abstract:

    We have previously shown that bracken fern (Pteridium aquilinum) has immunomodulatory effects on mouse natural killer (NK) cells by reducing cytotoxicity. Alternatively, it has been demonstrated that selenium can enhance NK cell activity. Therefore, the aims of the present study were to evaluate if Ptaquiloside, the main toxic component found in P. aquilinum, is responsible for the immunotoxic effects observed in mice, and if selenium supplementation could prevent or even reverse these effects. Male C57BL/6 mice were administered the P. aquilinum extract by daily gavage for 30 days, and histological analyses revealed a significant reduction in splenic white pulp area that was fully reversed by selenium treatment. In addition, mice administered Ptaquiloside by daily gavage for 14 days demonstrated the same reduction of NK cell activity as the P. aquilinum extract, and this reduction was prevented by selenium co-administration. Lastly, non-adherent splenic cells treated in vitro with an RPMI extract of P. aquilinum also showed diminished NK cell activity that was not only prevented by selenium co-treatment but also fully reversed by selenium post-treatment. The results of this study clearly show that the immunosuppressive effects of P. aquilinum are induced by Ptaquiloside and that selenium supplementation can prevent as well as reverse these effects.

Hans Christian Bruun Hansen - One of the best experts on this subject based on the ideXlab platform.

  • does the natural carcinogen Ptaquiloside degrade readily in groundwater
    Environmental Sciences Europe, 2021
    Co-Authors: Frederik Clausonkaas, Lars Holm Rasmussen, Bjarne W Strobel, Dan Nybro Lindqvist, Hans Christian Bruun Hansen
    Abstract:

    Ptaquiloside (PTA) is a natural carcinogen found in bracken ferns. PTA is released from the plants via soil to surface and groundwaters from where humans can be exposed via drinking water. Primary degradation of PTA is due to hydrolysis with formation of pterosin B (PTB). Temperature and pH determine the rate of hydrolysis under pure experimental conditions. To assess the applicability of the experimental model to natural groundwaters, PTA degradation kinetics were examined in a range of natural groundwaters at environmentally relevant conditions. PTA was quantified by UPLC-MS/MS. Over an 80-day study period, PTA half-lives ranged from 6.5 to 47 days (natural pH; 8.0 °C). The fastest degradation was observed for the most alkaline groundwaters with pH of around 8. Rates of degradation were well predicted using an existing mathematical model for hydrolysis. However, deviations from this model were found, especially at the extremes of the examined pH-range (4.7–8.2). The degree of conversion of PTA to PTB was close to unity around neutral pH. However, at slightly acidic conditions, formation of PTB could only count for 9% of the degraded PTA, indicating formation of other products. Degradation of PTA in groundwater is determined by pH and temperature, and PTA can prevail for months under slightly acid to neutral pH conditions. The existing laboratory-based model for PTA hydrolysis is generally applicable for groundwaters but needs further validation at high and low pH.

  • fate of Ptaquiloside a bracken fern toxin in cattle
    PLOS ONE, 2019
    Co-Authors: Paulo Cesar Reis Aranha, Lars Holm Rasmussen, Hans Christian Bruun Hansen, Godelind A Wolfjackel, H Jensen, Christian Friis
    Abstract:

    Ptaquiloside is a natural toxin present in bracken ferns (Pteridium sp.). Cattle ingesting bracken may develop bladder tumours and excrete genotoxins in meat and milk. However, the fate of Ptaquiloside in cattle and the link between Ptaquiloside and cattle carcinogenesis is unresolved. Here, we present the toxicokinetic profile of Ptaquiloside in plasma and urine after intravenous administration of Ptaquiloside and after oral administration of bracken. Administered intravenously Ptaquiloside, revealed a volume of distribution of 1.3 L kg-1 with a mean residence-time of 4 hours. A large fraction of Ptaquiloside was converted to non-toxic pterosin B in the blood stream. Both Ptaquiloside and pterosin B were excreted in urine (up to 41% of the dose). Oral administration of Ptaquiloside via bracken extract or dried ferns did not result in observations of Ptaquiloside in body fluids, indicating deglycosolidation in the rumen. Pterosin B was detected in both plasma and urine after oral administration. Hence, transport of carcinogenic Ptaquiloside metabolites over the rumen membrane is indicated. Pterosin B recovered from urine counted for 7% of the dose given intravenously. Heifers exposed to bracken for 7 days (2 mg Ptaquiloside kg-1) developed preneoplastic lesions in the urinary bladder most likely caused by genotoxic Ptaquiloside metabolites.

  • dissipation of pterosin b in acid soils tracking the fate of the bracken fern carcinogen Ptaquiloside
    Chemosphere, 2016
    Co-Authors: Eirini Skourtistathaki, Lars Holm Rasmussen, Frederik Clausonkaas, Kristian K Brandt, Hans Christian Bruun Hansen
    Abstract:

    Abstract Bracken ferns ( Pteridium spp.) are well-known for their carcinogenic properties, which are ascribed to the content of Ptaquiloside and Ptaquiloside-like substances. Ptaquiloside leach from the ferns and may cause contamination of drinking water. Pterosin B is formed by hydrolysis of Ptaquiloside. In soil, Pterosin B is adsorbed more strongly and it is expected to have a slower turnover than Ptaquiloside. We thus hypothesized that pterosin B may serve as an indicator for any past presence of Ptaquiloside. Pterosin B degradation was studied in acid forest soils from bracken-covered and bracken-free areas. Soil samples were incubated with pterosin B at 3 and 8 μg g −1 for 10 days, whereas sterile (autoclaved) samples were incubated for 23 days. Pterosin B showed unexpected fast degradation in soils with full degradation in topsoils in 2–5 days. Pterosin B dissipation followed the sum of two-first order reactions. The initial fast reaction with half-lives of 0.7–3.5 h contributed 11–59% of the total pterosin B degradation, while the slow reaction was 20–100 times slower than the fast reaction. Total dissipation half-lives were shorter for loamy sand (4 h) than for sandy loam soils (28 h). No degradation of pterosin B took place under sterile conditions assuming observed dissipation during the first 3 h could be attributed to irreversible sorption. Our results demonstrate that pterosin B is microbially degraded and that pterosin B is as unstable as Ptaquiloside and hence cannot be used as an indicator for former presence of Ptaquiloside in soil.

  • uplc ms ms determination of Ptaquiloside and pterosin b in preserved natural water
    Analytical and Bioanalytical Chemistry, 2016
    Co-Authors: Frederik Clausonkaas, Hans Christian Bruun Hansen, Bjarne W Strobel
    Abstract:

    The naturally occurring carcinogen Ptaquiloside and its degradation product pterosin B are found in water leaching from bracken stands. The objective of this work is to present a new sample preservation method and a fast UPLC-MS/MS method for quantification of Ptaquiloside and pterosin B in environmental water samples, employing a novel internal standard. A faster, reliable, and efficient method was developed for isolation of high purity Ptaquiloside and pterosin B from plant material for use as analytical standards, with purity verified by 1H-NMR. The chemical analysis was performed by cleanup and preconcentration of samples with solid phase extraction, before analyte quantification with UPLC-MS/MS. By including gradient elution and optimizing the liquid chromatography mobile phase buffer system, a total run cycle of 5 min was achieved, with method detection limits, including preconcentration, of 8 and 4 ng/L for Ptaquiloside and pterosin B, respectively. The use of loganin as internal standard improved repeatability of the determination of both analytes, though it could not be employed for sample preparation. Buffering raw water samples in situ with ammonium acetate to pH ∼5.5 decisively increased sample integrity at realistic transportation and storing conditions prior to extraction. Groundwater samples collected in November 2015 at the shallow water table below a Danish bracken stand were preserved and analyzed using the above methods, and PTA concentrations of 3.8 ± 0.24 μg/L (±sd, n = 3) were found, much higher than previously reported.

  • Ptaquiloside in irish bracken ferns and receiving waters with implications for land managers
    Molecules, 2016
    Co-Authors: Connie Odriscoll, Hans Christian Bruun Hansen, Carmel Ramwell, Brendan Harhen, Liam Morrison, Frederik Clausonkaas, Graeme Campbell, Jerome Sheahan, Bruce Misstear, Liwen Xiao
    Abstract:

    Ptaquiloside, along with other natural phytotoxins, is receiving increased attention from scientists and land use managers. There is an urgent need to increase empirical evidence to understand the scale of phytotoxin mobilisation and potential to enter into the environment. In this study the risk of Ptaquiloside to drinking water was assessed by quantifying Ptaquiloside in the receiving waters at three drinking water abstraction sites across Ireland and in bracken fronds surrounding the abstraction sites. We also investigated the impact of different management regimes (spraying, cutting and rolling) on Ptaquiloside concentrations at plot-scale in six locations in Northern Ireland, UK. Ptaquiloside concentrations were determined using recent advances in the use of LC-MS for the detection and quantification of Ptaquiloside. The results indicate that Ptaquiloside is present in bracken stands surrounding drinking water abstractions in Ireland, and Ptaquiloside concentrations were also observed in the receiving waters. Furthermore, spraying was found to be the most effective bracken management regime observed in terms of reducing Ptaquiloside load. Increased awareness is vital on the implications of managing land with extensive bracken stands.