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1.
Innate Immun ; 27(7-8): 543-552, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34812690

RESUMO

Acute lung injury (ALI) is associated with a high mortality due to inflammatory cell infiltration and lung edema. The development of ALI commonly involves the activation of NF-κB. Since bergamottin is a natural furanocoumarin showing the ability to inhibit the activation of NF-κB, in this study we aimed to determine the effect of bergamottin on ALI. RAW264.7 mouse macrophages were pre-treated with bergamottin and then stimulated with LPS. Macrophage inflammatory responses were examined. Bergamottin (50 mg/kg body mass) was intraperitoneally administrated to mice 12 h before injection of LPS, and the effect of bergamottin on LPS-induced ALI was evaluated. Our results showed that LPS exposure led to increased production of TNF-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which was impaired by bergamottin pre-treatment. In vivo studies confirmed that bergamottin pre-treatment suppressed LPS-induced lung inflammation and edema and reduced the levels of pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluids. Mechanistically, bergamottin blocked LPS-induced activation of NF-κB signaling in lung tissues. Additionally, bergamottin treatment reduced NF-κB p65 protein acetylation, which was coupled with induction of SIRT1 expression. In conclusion, our results reveal the anti-inflammatory property of bergamottin in preventing ALI. Induction of SIRT1 and inhibition of NF-κB underlies the anti-inflammatory activity of bergamottin.


Assuntos
Lesão Pulmonar Aguda , Furocumarinas , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Furocumarinas/efeitos adversos , Lipopolissacarídeos/farmacologia , Pulmão , Camundongos , NF-kappa B/metabolismo , Sirtuína 1
3.
J Nutr ; 150(6): 1535-1544, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32221600

RESUMO

BACKGROUND: In prior studies, higher citrus consumption was associated with higher risk of cutaneous malignant melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Furocoumarins, compounds with phototoxicity and photocarcinogenicity in citrus, may be responsible for the association. OBJECTIVES: The objective of the study was to investigate the association between furocoumarin intake and skin cancer risk. METHODS: A total of 47,453 men from the Health Professionals Follow-Up Study (HPFS) and 75,291 women from the Nurses' Health Study (NHS) with diet data collected every 2-4 y in the 2 prospective cohort studies were included. A furocoumarin food composition database for 7 common furocoumarins [bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxybergamottin (6'7'-DHB), epoxybergamottin, and bergamottin] was developed and used to calculate participants' cumulative average and energy-adjusted furocoumarin intake. Multivariate HRs and 95% CIs of the associations between furocoumarin intake and skin cancer risk were estimated using Cox proportional hazards models. Analyses were performed separately in each cohort as well as pooled using a fixed-effects model. RESULTS: Throughout follow-up (1984-2012 in the NHS and 1986-2012 in the HPFS), we identified 1593 melanoma, 4066 SCC, and 28,630 BCC cases. Higher intake of total furocoumarins was associated with an increased risk of BCC; the pooled HR comparing the top with the bottom quintile was 1.16 (95% CI: 1.11, 1.21; P-trend = 0.002). Higher intakes of bergaptol, bergapten, 6'7'-DHB, and bergamottin were also significantly associated with increased BCC risk. No significant associations were found between intake of total furocoumarins and the risks of SCC or melanoma. CONCLUSIONS: Intakes of total furocoumarins as well as some individual furocoumarins were associated with an increased risk of skin cancer, especially BCC, in 2 cohorts of US health professionals.


Assuntos
Citrus , Furocumarinas/administração & dosagem , Neoplasias Cutâneas/induzido quimicamente , Adulto , Feminino , Furocumarinas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/epidemiologia , Reino Unido , Estados Unidos/epidemiologia
6.
Nutr Cancer ; 72(1): 24-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31074648

RESUMO

Furocoumarins are a group of phototoxic compounds found in numerous edible plants. Data from cohort studies have suggested that consumption of certain furocoumarin-rich foods may increase skin cancer risk. However, no study has specifically tested this hypothesis by estimating furocoumarin intake and assessing its relationship with skin cancer. This study aimed to estimate average daily furocoumarin intake of US adults using the National Health and Nutrition Examination Survey (NHANES) 2003-2012 and to examine the relationship between furocoumarin intake and melanoma history. A database of the contents of seven furocoumarins in 29 popular foods was linked to dietary data in NHANES 2003-2012. Mean total intake of the selected furocoumarins among US adults was 81.4 µg/day (standard error = 5.5). A total of 75 participants reported a history of melanoma. Using non- and low consumers (<50th percentile) as a reference, and after adjusting for potential confounders, OR (with 95% confidence interval) of melanoma history for the top 10 percent, 80-90th percentiles, and 50-80th percentiles were 1.75 (0.43-7.20), 1.66 (0.39-7.16), and 0.90 (0.45-1.78), respectively. Furocoumarins are widely consumed among US adults, and a trend towards higher odds of melanoma history was observed among those with higher furocoumarin intake, although this relationship was not statistically significant.


Assuntos
Dieta/efeitos adversos , Furocumarinas/efeitos adversos , Melanoma/epidemiologia , Inquéritos Nutricionais/estatística & dados numéricos , Fármacos Fotossensibilizantes/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Melanoma/induzido quimicamente , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Estados Unidos/epidemiologia , Adulto Jovem
7.
Transfus Apher Sci ; 58(6): 102665, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31740165

RESUMO

BACKGROUND: Therapeutic Plasma Exchange (TPE) is the primary therapy of immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP). Efficacy and safety data for TPE of iTTP have been assessed with Quarantine and Solvent-Detergent inactivated (SD) plasma. Here, amotosalen-UVA pathogen inactivated (AI) plasma, also in routine use, was evaluated in iTTP. METHODS: We conducted a retrospective review of iTTP cases prospectively reported to the French national registry (2010-2013). Cases reviewed underwent TPE with ≥70% of either AI or SD plasma. The primary endpoint was time to platelet count recovery; secondary endpoints were related to follow-up (sustained remission, relapses, flare-ups and refractoriness). RESULTS: 30 Test patients were identified in the AI group which could be timely matched to 40 Control patients in the SD group. The groups were fairly comparable for clinical presentation. Major findings were: (i) iTTP patients were exposed to lower plasma volumes in the AI group than in the SD group; (ii) Recovery rates were comparable between the groups. Median time to platelet count recovery (>150 × 109/L) trended to be shorter in the AI group though non significantly. Tolerance of AI vs SD plasma was of comparable frequency and severity in either group. CONCLUSION: TPE with Amotosalen-inactivated plasma demonstrated therapeutic efficacy and tolerability for iTTP patients. In view of the retrospective design, confirmation of these results is required in larger prospective studies.


Assuntos
Detergentes/farmacologia , Furocumarinas/farmacologia , Plasma/metabolismo , Púrpura Trombocitopênica Trombótica/terapia , Adulto , Estudos de Coortes , Feminino , Furocumarinas/efeitos adversos , Humanos , Masculino , Troca Plasmática , Solventes , Resultado do Tratamento
8.
Biomed Pharmacother ; 120: 109401, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622950

RESUMO

Patients with cancer survivors are at increased risk of cardiovascular disease(CVD). Cardio-oncology has developed as a new discipline with the advances in cancer treatment. There are many new challenges for the clinician and a new frontier for research and investigation. There is an urgent need for further study on the prevention of cardiovascular toxicity. Imperatorin (IMP) is a natural form of coumarin and extract from several plants with diver's pharmacokinetic effects, including antioxidant and anti-inflammatory properties. This review focus on the molecular mechanisms and pharmacological effects of Imperatorin maybe provide potential cancer and cardiovascular protection that targets IMP. Further studies are required to elucidate the entire spectrum of cytotoxic activities of these compounds to validate and expand their preclinical and clinical applications and to clarify the potential role of IMP.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Furocumarinas/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Antioxidantes/uso terapêutico , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Furocumarinas/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais
12.
J Eur Acad Dermatol Venereol ; 33(1): 56-62, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29953667

RESUMO

First described in 1961, photoonycholysis (PO) is a rare nail alteration that may result from drug intake, from topical aminolevulinate photodynamic therapy or from photosensitive conditions such as porphyria or pseudoporphyria. Spontaneous PO is rare. This review updates the numerous causes of PO and highlights some new ways producing this condition. Four different types of PO are clearly recognized without relationship with the responsible drug. An updated list of potential inducing drug is provided. Some practical points on PO have been raised. The inability to reproduce photoonycholysis experimentally should be emphasized, and the pathogenesis of PO still needs to be clarified.


Assuntos
Antibacterianos/efeitos adversos , Furocumarinas/efeitos adversos , Onicólise/etiologia , Terapia PUVA/efeitos adversos , Porfirias/complicações , Humanos , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos
13.
Food Chem Toxicol ; 122: 163-171, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30316841

RESUMO

Furocoumarins are a class of compounds produced by several plant species, including some popularly consumed by humans. Furocoumarins are known to be well absorbed from food sources, and can be rapidly distributed into several tissues including the skin. In human skin, when exposed to UV radiation, furocoumarins may become photoactivated and form interstrand crosslinks with DNA, thereby disrupting DNA transcription. Because of this property, furocoumarins have been combined as topical or oral agents with UV irradiation as a phototherapy to treat multiple skin conditions, yet these treatments have been shown to increase risk of both melanoma and non-melanoma skin cancer. Whether or not dietary furocoumarin exposure may confer the same risk is not yet known. This review summarizes the current evidence regarding the activities of ingested furocoumarins, with particular focus on how dietary furocoumarins are absorbed, metabolized, and distributed throughout the body, and their interactions with various cellular components that may underlie a potential relationship with skin cancer.


Assuntos
Furocumarinas/farmacocinética , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Cutâneas/etiologia , Animais , Carcinógenos/toxicidade , Adutos de DNA/química , Replicação do DNA/efeitos dos fármacos , Exposição Dietética , Furocumarinas/efeitos adversos , Humanos , Neoplasias Induzidas por Radiação/genética , Fotoquimioterapia , Plantas Comestíveis/química , Neoplasias Cutâneas/genética , Distribuição Tecidual , Raios Ultravioleta
16.
Wounds ; 29(12): E118-E124, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29324427

RESUMO

INTRODUCTION: Phytophototoxic dermatitis is a strong phototoxic reaction to ultraviolet A (UV-A) radiation exposure after cutaneous contact with citrus fruit containing furocoumarins, leading to skin injury. At the Arizona Burn Center (Phoenix, AZ), the majority of these injuries are managed in the outpatient setting. CASE REPORT: The authors present a pediatric admission for burn-like injuries following prolonged cutaneous exposure to lemons while playing in the Arizona sunshine. A 7-year-old girl playing in her backyard squeezed lemon juice onto her skin while in the hot Arizona sunshine; within 24 hours, the child experienced pain, erythema, and blistering to multiple areas of her skin. She was admitted to the authors' burn center for wound care and pain control. She had scattered first-degree and second-degree burn-like lesions to her face, neck, and chest as well as bilateral forearms, hands, lower extremities, and feet. After blister debridement, appropriate dressing care, and pain medication, the patient was discharged home after 4 days of hospitalization with appropriate clinical follow-up. CONCLUSIONS: Burn-like lesions caused by furocoumarins after cutaneous absorption and UV-A exposure are known clinical entities in Arizona. The sequential progression from erythema to blisters equivalent to second-degree burn-like lesions to cutaneous hyperpigmentation is a well-described clinical triad. Meticulous wound care and pain control for the treatment of these burn-like lesions are essential as is the need for the wound care specialist to be well versed on this topic to quickly identify the etiology of the injury, thereby avoiding misdiagnosing the patient with nonaccidental traumatic injuries.


Assuntos
Queimaduras/etiologia , Citrus/efeitos adversos , Dermatite Fototóxica/etiologia , Furocumarinas/efeitos adversos , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Administração Tópica , Arizona , Queimaduras/patologia , Queimaduras/terapia , Criança , Maus-Tratos Infantis , Citrus/química , Desbridamento , Dermatite Fototóxica/patologia , Dermatite Fototóxica/terapia , Diagnóstico Diferencial , Feminino , Furocumarinas/química , Humanos , Resultado do Tratamento
17.
Pol Merkur Lekarski ; 41(243): 165-168, 2016 Sep 29.
Artigo em Polonês | MEDLINE | ID: mdl-27755521

RESUMO

Sosnowsky's hogweed (Heracleum sosnowskyi Manden.) is a genus of plants in the family Apiaceae which also includes Giant Hogweed (Heracleum mantegazzianum Sommier and Levier). They are both found in Central Europe, mainly in neglected green areas or riversides. Sosnowsky's hogweed was brought to Poland from the Soviet Union in the 1950s to be used in animal feed production. Intended goals couldn't be achieved and the plant spread throughout grounds distant to the primarily cultivated lands. Sosnowsky's hogweed is especially hazardous in direct contact with human skin. It results from the content of photoallergic substances called furanocoumarins in its essential oil. Clinically it is presented as burns, mainly of 2nd and 3rd degree. They mostly occur on the face, upper and lower limbs. Typical symptoms include pain, redness, swelling and heat in the area of exposure. Their extent depends on burn's depth and area and also on time of exposure to plant's toxins. In this article we present Sosnowsky's hogweed's activity and its influence on human health.


Assuntos
Furocumarinas/toxicidade , Heracleum/química , Fármacos Fotossensibilizantes/toxicidade , Queimadura Solar/etiologia , Furocumarinas/efeitos adversos , Heracleum/toxicidade , Humanos , Fármacos Fotossensibilizantes/efeitos adversos
18.
Pol Merkur Lekarski ; 40(238): 269-72, 2016 Apr.
Artigo em Polonês | MEDLINE | ID: mdl-27137831

RESUMO

Drugs with side effects affecting vision are often used in the treatment of skin disorders. The study evaluated principal groups of medicines which may negatively influence vision and the eye itself. Antimalaric drugs may cause a number of disorders of vision and a diagnosed retinophaty is an absolute contraindication. Retinoids often cause a dry eye condition, which results in intolerance to wearing contact lenses. They can also be a cause of poor nightly vision. Psoralens, used in photochemotherapy, can penetrate to the frontal part of the eye, inducing clouding of the lens and cataract. Glucocorticosteroids, often used in skin conditions, increase intraocular pressure, which may result in development of glaucoma. Methotrexate may also cause complications, such as eyelid edema, conjunctival hyperemia, increased lacrimation and photophobia. A prolonged use of tetracyclines may induce side effect in eye organs. Swelling of the optic nerve head with subsequent decreased vision, and even accumulate of metabolites of tetracycline within the conjunctival were observed. In the study a distinction was made between the medications which may lead to a temporary visual impairment and the medication with a side effect lasting beyond the treatment. It was pointed out that some of the side effects could be avoided or minimised by not combining retinoids and tetracyclines or with the use of protective eyewear during photochemotherapy. An examination by ophthalmologist is a crucial step prior to the treatment with chloroquine, hydroxychloroquine or psoralens. Regular eye exams are necessary when using, especially in a protracted fashion, most of the discussed drugs. Finally, the cooperation between dermatologist and ophthalmologist is fundamental for ensuring patient's safety.


Assuntos
Oftalmopatias/induzido quimicamente , Dermatopatias/tratamento farmacológico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Oftalmopatias/prevenção & controle , Furocumarinas/efeitos adversos , Furocumarinas/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Retinoides/efeitos adversos , Retinoides/uso terapêutico , Tetraciclinas/efeitos adversos , Tetraciclinas/uso terapêutico
20.
Transfusion ; 56(1): 41-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26358662

RESUMO

BACKGROUND: Fresh-frozen plasma (FFP) transfusion carries a risk of viral transmission from donor to recipient. Riboflavin (Mirasol) and amotosalen (Intercept) are two pathogen inactivation (PI) methods that may enhance the safety of FFP for transfusion. Our study investigated the effects of Mirasol and Intercept treatment on fibrin formation and clot structure. STUDY DESIGN AND METHODS: FFP underwent either Mirasol or Intercept treatment, and aliquots were taken before addition of the compound, before illumination (after addition of compound only), and after treatment (addition of compound plus illumination). All samples underwent turbidimetric analysis, lysis analysis, assessment of clot permeation, and analysis by laser scanning confocal microscopy. RESULTS: After treatment, there was a decrease in optical density of the fibrin network for Mirasol and Intercept, lag time to fibrin formation was prolonged for Mirasol and lysis time for Intercept, clot permeability was significantly decreased, and clot density was increased for both. CONCLUSIONS: Our study shows that plasma treated with Mirasol and Intercept produces denser clots consisting of thinner fibers and warrants further studies to evaluate the clinical significance of these structural changes in fibrin clot formation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Segurança do Sangue/efeitos adversos , Fibrina/efeitos dos fármacos , Furocumarinas/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Plasma/efeitos dos fármacos , Riboflavina/efeitos adversos , Segurança do Sangue/métodos , Humanos , Plasma/fisiologia , Plasma/virologia , Inativação de Vírus
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