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1.
BMC Complement Altern Med ; 16(1): 399, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27769229

RESUMO

BACKGROUND: Cancer is a major disease worldwide, and many patients use complementary and alternative treatments. The purpose of this study was to identify the herbal remedies and functional foods used as complementary medicine by prostate, breast and colorectal cancer patients at speciality care facilities in Trinidad. We also sought to determine how patients rated the efficacy of these modalities compared with conventional treatment. METHODS: A descriptive, cross-sectional survey was conducted using an interviewer-administered pilot-tested de novo questionnaire during the period June to August 2012 at two speciality treatment centres on the island. Data was analysed using χ2 analyses. RESULTS: Among the 150 patients who reported use of herbal remedies/functional foods, soursop (Annona muricata L.) was the most popular; with 80.7 % using the leaves, bark, fruit and seeds on a regular basis. Other common herbal remedies/functional foods included wheatgrass (Triticum aestivum L.), saffron (Crocus sativus L.) and Aloe vera (L.) Burm. f. The most commonly used functional foods were beetroot (Beta vulgaris L.), carrots (Daucus carata L.) and papaya (Carica papaya L.) used by 43.3 % of patients; and these were mostly blended as a mixture. Herbal remedies and functional foods were used on a daily basis and patients believed that this modality was equally (32.0 %) or more efficacious (14.7 %) than conventional treatment. CONCLUSIONS: This survey identified the most common herbal remedies and functional foods used among prostate, breast and colorectal cancer patients in Trinidad. Although functional foods rarely pose a problem, herbs may interact with conventional chemotherapy and physicians need to inform patients regarding probable herb-drug interactions.


Assuntos
Antineoplásicos/uso terapêutico , Alimento Funcional/estatística & dados numéricos , Neoplasias , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/dietoterapia , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Trinidad e Tobago/epidemiologia , Adulto Jovem
2.
Maturitas ; 68(3): 256-63, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21237589

RESUMO

OBJECTIVE: Many postmenopausal women use herbal remedies and dietary supplements to counteract menopausal symptoms, including the decline in cognitive function. The aim of this systematic review is to evaluate the evidence regarding the efficacy of herbal and dietary supplements on cognition in menopause. DESIGN: Randomized clinical trials (RCTs) of herbal medicines and dietary supplements were identified using the Medline, EMBASE, AMED, PsycINFO, CINAHL and The Cochrane Library 2010 (Issue 2) electronic databases and by hand searches. Data were independently extracted and evaluated by two reviewers. Risk of bias was assessed by two independent reviewers using the Cochrane Collaboration tool. RESULTS: Twelve RCTs were included and five of these suggest that isoflavone, soy and Gingko biloba supplementation may improve cognition in postmenopausal women. However, most of the included studies had serious methodological flaws which demand a cautious interpretation of these findings. CONCLUSIONS: The evidence that herbal and dietary supplements might positively affect the cognitive decline during the menopause is not compelling.


Assuntos
Transtornos Cognitivos/prevenção & controle , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Ginkgo biloba , Fitoterapia , Extratos Vegetais/uso terapêutico , Feminino , Humanos , Isoflavonas/uso terapêutico , Menopausa , Extratos Vegetais/farmacologia , Resultado do Tratamento
4.
Artigo em Inglês | MedCarib | ID: med-17684

RESUMO

A letter to the editor is presented in response to the article regarding herbal self-medication at Primary Health Care Facilities in Trinidad, which appeared in previous issue.


Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Humanos , Masculino , Feminino , Medicina Herbária , Plantas Medicinais , Atenção Primária à Saúde , Trinidad e Tobago
5.
BMC Complement Altern Med ; 7: 4, 2007 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-17286858

RESUMO

BACKGROUND: The increasing global popularity of herbal remedies requires further investigation to determine the probable factors driving this burgeoning phenomenon. We propose that the users' perception of efficacy is an important factor and assessed the perceived efficacy of herbal remedies by users accessing primary health facilities throughout Trinidad. Additionally, we determined how these users rated herbal remedies compared to conventional allopathic medicines as being less, equally or more efficacious. METHODS: A descriptive cross-sectional study was undertaken at 16 randomly selected primary healthcare facilities throughout Trinidad during June-August 2005. A de novo, pilot-tested questionnaire was interviewer-administered to confirmed herbal users (previous or current). Stepwise multiple regression analysis was done to determine the influence of predictor variables on perceived efficacy and comparative efficacy with conventional medicines. RESULTS: 265 herbal users entered the study and cited over 100 herbs for the promotion of health/wellness and the management of specific health concerns. Garlic was the most popular herb (in 48.3% of the sample) and was used for the common cold, cough, fever, as 'blood cleansers' and carminatives. It was also used in 20% of hypertension patients. 230 users (86.8%) indicated that herbs were efficacious and perceived that they had equal or greater efficacy than conventional allopathic medicines. Gender, ethnicity, income and years of formal education did not influence patients' perception of herb efficacy; however, age did (p = 0.036). Concomitant use of herbs and allopathic medicines was relatively high at 30%; and most users did not inform their attending physician. CONCLUSION: Most users perceived that herbs were efficacious, and in some instances, more efficacious than conventional medicines. We suggest that this perception may be a major contributing factor influencing the sustained and increasing popularity of herbs. Evidence-based research in the form of randomized controlled clinical trials should direct the proper use of herbs to validate (or otherwise) efficacy and determine safety. In the Caribbean, most indigenous herbs are not well investigated and this points to the urgent need for biomedical investigations to assess the safety profile and efficacy of our popular medicinal herbs.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Fitoterapia/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Quimioterapia Combinada , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Análise de Regressão , Fatores Socioeconômicos , Resultado do Tratamento , Trinidad e Tobago
6.
BMC complementary and alternative medicine ; 7(4): [1-9], Feb. 2007. tab
Artigo em Inglês | MedCarib | ID: med-17705

RESUMO

BACKGROUND: The increasing global popularity of herbal remedies requires further investigation to determine the probable factors driving this burgeoning phenomenon. We propose that the users' perception of efficacy is an important factor and assessed the perceived efficacy of herbal remedies by users accessing primary health facilities throughout Trinidad. Additionally, we determined how these users rated herbal remedies compared to conventional allopathic medicines as being less, equally or more efficacious. METHODS: A descriptive cross-sectional study was undertaken at 16 randomly selected primary healthcare facilities throughout Trinidad during June-August 2005. A de novo, pilot-tested questionnaire was interviewer-administered to confirmed herbal users (previous or current). Stepwise multiple regression analysis was done to determine the influence of predictor variables on perceived efficacy and comparative efficacy with conventional medicines. RESULTS: 265 herbal users entered the study and cited over 100 herbs for the promotion of health/wellness and the management of specific health concerns. Garlic was the most popular herb (in 48.3% of the sample) and was used for the common cold, cough, fever, as 'blood cleansers' and carminatives. It was also used in 20% of hypertension patients. 230 users (86.8%) indicated that herbs were efficacious and perceived that they had equal or greater efficacy than conventional allopathic medicines. Gender, ethnicity, income and years of formal education did not influence patients' perception of herb efficacy; however, age did (p = 0.036). Concomitant use of herbs and allopathic medicines was relatively high at 30%; and most users did not inform their attending physician. CONCLUSION: Most users perceived that herbs were efficacious, and in some instances, more efficacious than conventional medicines. We suggest that this perception may be a major contributing factor influencing the sustained and increasing popularity of herbs. Evidence-based research in the form of randomized controlled clinical trials should direct the proper use of herbs to validate (or otherwise) efficacy and determine safety. In the Caribbean, most indigenous herbs are not well investigated and this points to the urgent need for biomedical investigations to assess the safety profile and efficacy of our popular medicinal herbs.


Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Estudos Transversais , Quimioterapia Combinada , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Relações Médico-Paciente , Medicina Herbária , Fitoterapia , Atenção Primária à Saúde , Análise de Regressão , Fatores Socioeconômicos , Resultado do Tratamento , Trinidad e Tobago
7.
BMC Complement Altern Med ; 5: 20, 2005 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-16297236

RESUMO

BACKGROUND: The unprecedented global increase in the use of herbal remedies is set to continue apace well into the foreseeable future. This raises important public health concerns, especially as it relates to safety issues including adverse effects and herb-drug interactions. Most Western-trained physicians are ignorant of the risks and benefits of this healthcare modality and assessment of acceptance and knowledge would identify appropriate intervention strategies to improve physician-patient communication in this area. METHODS: A cross-sectional survey was done using an interviewer-administered pilot tested de novo questionnaire at six public hospitals in Trinidad between May-July 2004. The questionnaire utilized weighed questions to quantify acceptance (maximum score = 14 points) and knowledge (maximum score = 52 points). Acceptance and knowledge scores were analyzed using the ANOVA and Tukey's tests. RESULTS: Of 192 physicians interviewed, most (60.4%) believed that herbal remedies were beneficial to health. Respondents had relatively high acceptance levels (mean = 5.69 +/- 0.29 points or 40% of total possible score) and poor knowledge (mean = 7.77 +/- 0.56 points or 15% of total possible score). Seventy-eight physicians (40.6%) admitted having used herbs in the past, and 60 of these (76.9%) were satisfied with the outcome. Although 52 physicians (27.1%) recommended the use of herbs to their patients only 29 (15.1%) were able to identify at least one known herb-drug interaction. CONCLUSION: The use of herbal remedies is relatively high in Trinidad, as throughout the world, and most patients self-medicate with or without the knowledge of their attending physician. Surprisingly, we demonstrated relatively high acceptance levels and use of herbs among physicians in Trinidad. This interesting scenario of high acceptance levels and poor knowledge creates a situation that demands urgent intervention. We recommend educational intervention to narrow the gap between acceptance and knowledge so that physicians would be adequately equipped to communicate with their patients on this modality. The integration of herbal medicine into the curriculum of medical schools, continuing education programs and the availability of reputable pharmacopoeias for referencing at public health institutions are useful instruments that can be used to close this gap and promote improved physician-patient communication.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Medicina Herbária/educação , Hospitais Públicos/estatística & dados numéricos , Fitoterapia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Acesso à Informação , Atitude do Pessoal de Saúde , Estudos Transversais , Currículo , Educação Continuada/tendências , Humanos , Relações Médico-Paciente , Projetos Piloto , Vigilância da População , Populus , Inquéritos e Questionários , Trinidad e Tobago
8.
BMC complementary and alternative medicine ; 5(20): 9p, 18 Nov. 2005. tab
Artigo em Inglês | MedCarib | ID: med-17423

RESUMO

BACKGROUND: The unprecedented global increase in the use of herbal remedies is set to continue apace well into the foreseeable future. This raises important public health concerns, especially as it relates to safety issues including adverse effects and herb-drug interactions. METHODS: A cross-sectional survey was done using an interviewer-administered pilot tested de novo questionnaire at six public hospitals in Trinidad between May–July 2004. The questionnaire utilized weighed questions to quantify acceptance (maximum score = 14 points) and knowledge (maximum score = 52 points). Acceptance and knowledge scores were analyzed using the ANOVA and Tukey's tests. RESULTS: Of 192 physicians interviewed, most (60.4 per cent) believed that herbal remedies were beneficial to health. Respondents had relatively high acceptance levels (mean = 5.69 ñ 0.29 points or 40 per cent of total possible score) and poor knowledge (mean = 7.77 ñ 0.56 points or 15 per cent of total possible score). Seventy-eight physicians (40.6 per cent) admitted having used herbs in the past, and 60 of these (76.9 per cent) were satisfied with the outcome. Although 52 physicians (27.1 per cent) recommended the use of herbs to their patients only 29 (15.1 per cent) were able to identify at least one known herb-drug interaction. CONCLUSION: Surprisingly, we demonstrated relatively high acceptance levels and use of herbs among physicians in Trinidad. This interesting scenario of high acceptance levels and poor knowledge creates a situation that demands urgent intervention. The integration of herbal medicine into the curriculum of medical schools, continuing education programs and the availability of reputable pharmacopoeias for referencing at public health institutions are useful instruments that can be used to close this gap and promote improved physician-patient communication.


Assuntos
Humanos , Medicina Herbária/estatística & dados numéricos , Medicina Herbária/tendências , Educação Médica/estatística & dados numéricos
9.
Mutation research ; 579(1-2): 182-188, Nov. 2005. graf
Artigo em Inglês | MedCarib | ID: med-17447

RESUMO

A synergistic depletion of glutathione has been suggested to be one critical factor in the hepatic injury in mice induced by non-toxic doses of paracetamol (APAP) when co-administered with  -adrenergic agonists. Prazosin (an  -adrenergic antagonist) could confer hepatoprotection following a toxic APAP dose (530 mg/kg) by increasing glutathione levels and enhancing bioinactivation by glucuronidation and glutathione conjugation. The effect of prazosin pre-treatment on APAP-induced gluthathione depletion and bioinactivation in vivo was assessed. Prazosin (15 mg/kg) pre-treatment provided protection against APAP-induced hepatic injury as evidenced by a significant decrease in serum transaminase (ALT) levels after 5 h (p < 0.05). Interestingly, prazosin pre-treatment did not prevent the dramatic depletion of glutathione by high dose APAP and it had no effect on the quantity of the glutathione conjugate formed. However, prazosin pre-treatment caused a significant increase in recovery of the administered dose (530 mg/kg) as the glucuronide metabolite (p < 0.05). UDP-glucuronosyltransferase (UGT) is involved in the bioinactivation of APAP by glucuronidation and we showed that prazosin had no effect on microsomal UGT kinetics. Thus, prazosin had no effect on either APAP-mediated glutathione depletion or the extent of APAP-glutathione conjugate formation and may be affecting other mechanisms to reduce oxidative stress caused by a toxic dose of APAP


Assuntos
Camundongos , Acetaminofen/efeitos adversos , Relação Dose-Resposta a Droga , Substâncias Protetoras/farmacologia , Glutationa/metabolismo , Falência Hepática/patologia , Glucuronosiltransferase/metabolismo , Iminas/metabolismo , Camundongos Endogâmicos
10.
Mutat Res ; 579(1-2): 182-8, 2005 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-16054166

RESUMO

A synergistic depletion of glutathione has been suggested to be one critical factor in the hepatic injury in mice induced by non-toxic doses of paracetamol (APAP) when co-administered with alpha-adrenergic agonists. Prazosin (an alpha-adrenergic antagonist) could confer hepatoprotection following a toxic APAP dose (530 mg/kg) by increasing glutathione levels and enhancing bioinactivation by glucuronidation and glutathione conjugation. The effect of prazosin pre-treatment on APAP-induced gluthathione depletion and bioinactivation in vivo was assessed. Prazosin (15 mg/kg) pre-treatment provided protection against APAP-induced hepatic injury as evidenced by a significant decrease in serum transaminase (ALT) levels after 5h (p<0.05). Interestingly, prazosin pre-treatment did not prevent the dramatic depletion of glutathione by high dose APAP and it had no effect on the quantity of the glutathione conjugate formed. However, prazosin pre-treatment caused a significant increase in recovery of the administered dose (530 mg/kg) as the glucuronide metabolite (p<0.05). UDP-glucuronosyltransferase (UGT) is involved in the bioinactivation of APAP by glucuronidation and we showed that prazosin had no effect on microsomal UGT kinetics. Thus, prazosin had no effect on either APAP-mediated glutathione depletion or the extent of APAP-glutathione conjugate formation and may be affecting other mechanisms to reduce oxidative stress caused by a toxic dose of APAP.


Assuntos
Acetaminofen/efeitos adversos , Hepatopatias/prevenção & controle , Prazosina/farmacologia , Substâncias Protetoras/farmacologia , Agonistas alfa-Adrenérgicos/efeitos adversos , Antagonistas Adrenérgicos alfa/farmacologia , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Analgésicos não Narcóticos/efeitos adversos , Animais , Benzoquinonas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas , Relação Dose-Resposta a Droga , Glucuronosiltransferase/efeitos dos fármacos , Glucuronosiltransferase/metabolismo , Glutationa/metabolismo , Iminas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos
11.
BMC Complement Altern Med ; 5: 3, 2005 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-15713232

RESUMO

BACKGROUND: There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. METHODS: A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. RESULTS: Fifty-eight out of 191 patients (30.4%) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5% of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6%) obtained herbs from their backyards or the supermarket; only 14 patients (24.1%) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7%), and only 10.3% consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. CONCLUSIONS: Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments.


Assuntos
Asma/terapia , Fitoterapia/estatística & dados numéricos , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Adulto , Aloe , Asma/tratamento farmacológico , Cannabis , Estudos Transversais , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Alho , Humanos , Masculino , Pessoa de Meia-Idade , Plantas Medicinais , Trinidad e Tobago
12.
BMC complementary medicine ; 5(3): 8p, 15 Feb. 2005. tab
Artigo em Inglês | MedCarib | ID: med-17425

RESUMO

Background: There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. Methods: A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. Results: Fifty-eight out of 191 patients (30.4 per cent) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5 per cent of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6 per cent) obtained herbs from their backyards or the supermarket; only 14 patients (24.1 per cent) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7 per cent), and only 10.3 per cent consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. Conclusions: Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments.


Assuntos
Humanos , Plantas Medicinais/efeitos dos fármacos , Plantas Medicinais/fisiologia , Asma/tratamento farmacológico , Trinidad e Tobago/epidemiologia
13.
BMC complementary and alternative medicine ; 5(3): 8p, Feb.15, 2005. tab
Artigo em Inglês | MedCarib | ID: med-17446

RESUMO

BACKGROUND: There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. METHODS: A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. RESULTS: Fifty-eight out of 191 patients (30.4 per cent) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5 per cent of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6 per cent) obtained herbs from their backyards or the supermarket; only 14 patients (24.1 per cent) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7 per cent), and only 10.3 per cent consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. CONCLUSIONS: Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments.


Assuntos
Humanos , Plantas Medicinais/fisiologia , Asma/tratamento farmacológico , Asma/patologia , Trinidad e Tobago/epidemiologia , Região do Caribe
14.
Hepatology ; 39(5): 1267-76, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15122755

RESUMO

The transcription factor NF-E2-related factor 2 (Nrf2) plays an essential role in the mammalian response to chemical and oxidative stress through induction of hepatic phase II detoxification enzymes and regulation of glutathione (GSH). Enhanced liver damage in Nrf2-deficient mice treated with acetaminophen suggests a critical role for Nrf2; however, direct evidence for Nrf2 activation following acetaminophen exposure was previously lacking. We show that acetaminophen can initiate nuclear translocation of Nrf2 in vivo, with maximum levels reached after 1 hour, in a dose dependent manner, at doses below those causing overt liver damage. Furthermore, Nrf2 was shown to be functionally active, as assessed by the induction of epoxide hydrolase, heme oxygenase-1, and glutamate cysteine ligase gene expression. Increased nuclear Nrf2 was found to be associated with depletion of hepatic GSH. Activation of Nrf2 is considered to involve dissociation from a cytoplasmic inhibitor, Kelch-like ECH-associated protein 1 (Keap1), through a redox-sensitive mechanism involving either GSH depletion or direct chemical interaction through Michael addition. To investigate acetaminophen-induced Nrf2 activation we compared the actions of 2 other GSH depleters, diethyl maleate (DEM) and buthionine sulphoximine (BSO), only 1 of which (DEM) can function as a Michael acceptor. For each compound, greater than 60% depletion of GSH was achieved; however, in the case of BSO, this depletion did not cause nuclear translocation of Nrf2. In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH.


Assuntos
Acetaminofen/farmacologia , Analgésicos não Narcóticos/farmacologia , Proteínas de Ligação a DNA/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transativadores/metabolismo , Animais , Northern Blotting , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Masculino , Maleatos/farmacologia , Camundongos , Camundongos Endogâmicos , Fator 2 Relacionado a NF-E2 , Transativadores/genética
15.
Hepatology ; 39(5): 1267-1276, Apr 2004. grafilus
Artigo em Inglês | MedCarib | ID: med-17556

RESUMO

The transcription factor NF-E2-related factor 2 (Nrf2) plays an essential role in the mammalian response to chemical and oxidative stress through induction of hepatic phase II detoxification enzymes and regulation of glutathione (GSH). Enhanced liver damage in Nrf2-deficient mice treated with acetaminophen suggests a critical role for Nrf2; however, direct evidence for Nrf2 activation following acetaminophen exposure was previously lacking. We show that acetaminophen can initiate nuclear translocation of Nrf2 in vivo, with maximum levels reached after 1 hour, in a dose dependent manner, at doses below those causing overt liver damage. Furthermore, Nrf2 was shown to be functionally active, as assessed by the induction of epoxide hydrolase, heme oxygenase-1, and glutamate cysteine ligase gene expression. Increased nuclear Nrf2 was found to be associated with depletion of hepatic GSH. Activation of Nrf2 is considered to involve dissociation from a cytoplasmic inhibitor, Kelch-like ECH-associated protein 1 (Keap1), through a redox-sensitive mechanism involving either GSH depletion or direct chemical interaction through Michael addition. To investigate acetaminophen-induced Nrf2 activation we compared the actions of 2 other GSH depleters, diethyl maleate (DEM) and buthionine sulphoximine (BSO), only 1 of which (DEM) can function as a Michael acceptor. For each compound, greater than 60% depletion of GSH was achieved; however, in the case of BSO, this depletion did not cause nuclear translocation of Nrf2. In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH.


Assuntos
Camundongos , Acetaminofen , Acetaminofen/farmacologia , Fator 2 Relacionado a NF-E2/farmacologia , Camundongos/fisiologia
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