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1.
Cochrane Database Syst Rev ; 5: CD007411, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506389

RESUMO

BACKGROUND: The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility. OBJECTIVES: To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men. SEARCH METHODS: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, and two trial registers were searched on 15 February 2021, together with reference checking and contact with experts in the field to identify additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment, or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included men with idiopathic infertility and normal semen parameters or fertile men attending a fertility clinic because of female partner infertility. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes. MAIN RESULTS: We included 90 studies with a total population of 10,303 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing medically assisted reproduction (MAR). Investigators compared and combined 20 different oral antioxidants. The evidence was of 'low' to 'very low' certainty: the main limitation was that out of the 67 included studies in the meta-analysis only 20 studies reported clinical pregnancy, and of those 12 reported on live birth. The evidence is current up to February 2021. Live birth: antioxidants may lead to increased live birth rates (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.07 to 1.91, P = 0.02, 12 RCTs, 1283 men, I2 = 44%, very low-certainty evidence). Results in the studies contributing to the analysis of live birth rate suggest that if the baseline chance of live birth following placebo or no treatment is assumed to be 16%, the chance following the use of antioxidants is estimated to be between 17% and 27%. However, this result was based on only 246 live births from 1283 couples in 12 small or medium-sized studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.22, 95% CI 0.85 to 1.75, 827 men, 8 RCTs, P = 0.27, I2 = 32%). Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 1.89, 95% CI 1.45 to 2.47, P < 0.00001, 20 RCTs, 1706 men, I2 = 3%, low-certainty evidence) compared with placebo or no treatment. This suggests that, in the studies contributing to the analysis of clinical pregnancy, if the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 15%, the chance following the use of antioxidants is estimated to be between 20% and 30%. This result was based on 327 clinical pregnancies from 1706 couples in 20 small studies. Adverse events Miscarriage: only six studies reported on this outcome and the event rate was very low. No evidence of a difference in miscarriage rate was found between the antioxidant and placebo or no treatment group (OR 1.46, 95% CI 0.75 to 2.83, P = 0.27, 6 RCTs, 664 men, I2 = 35%, very low-certainty evidence). The findings suggest that in a population of subfertile couples, with male factor infertility, with an expected miscarriage rate of 5%, the risk of miscarriage following the use of an antioxidant would be between 4% and 13%. Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal discomfort when compared with placebo or no treatment (OR 2.70, 95% CI 1.46 to 4.99, P = 0.002, 16 RCTs, 1355 men, I2 = 40%, low-certainty evidence). This suggests that if the chance of gastrointestinal discomfort following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 7%. However, this result was based on a low event rate of 46 out of 1355 men in 16 small or medium-sized studies, and the certainty of the evidence was rated low and heterogeneity was high. We were unable to draw conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions. AUTHORS' CONCLUSIONS: In this review, there is very low-certainty evidence from 12 small or medium-sized randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-certainty evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal discomfort, based on very low-certainty evidence. Subfertile couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials studying infertile men and reporting on pregnancy and live births are still required to clarify the exact role of antioxidants.


Assuntos
Aborto Espontâneo , Infertilidade Feminina , Infertilidade Masculina , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Idoso , Antioxidantes/efeitos adversos , Criança , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/etiologia , Nascido Vivo/epidemiologia , Masculino , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez , Adulto Jovem
2.
Oxid Med Cell Longev ; 2022: 4943965, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509836

RESUMO

Pharmacological studies revealed that cedrol, a natural sesquiterpene, has antioxidant, anti-inflammatory, and analgesic properties. This study is aimed at evaluating the potential antiarthritic activity of cedrol in a rat experimental model of arthritis induced by using complete Freund's adjuvant (CFA). Arthritis was induced in Wistar rats by CFA (0.1 ml) injection. Cedrol (10 and 20 mg/kg) and indomethacin (5 mg/kg) were orally administered from day one and continued for 21 days. The antiarthritic activity was assessed through mechanical allodynia and thermal hyperalgesia responses, paw edema assessment, and arthritis scores. Serum TNF-α and IL-1ß levels were measured for the evaluation of inflammation. Furthermore, serum oxidative stress markers, including malondialdehyde (MDA) and thiol levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were also assessed. Oral administration of cedrol and indomethacin significantly decreased paw edema and arthritis score. Besides, cedrol and indomethacin significantly decreased pain responses. In the serum of the CFA group, TNF-α, IL-1ß, and MDA were higher, while thiol and SOD and GPx were lower than the control group. Treatment by cedrol and indomethacin corrected the biochemical parameters in the serum. In this study, cedrol offers potential antiarthritic properties through its anti-inflammatory and antioxidant effects.


Assuntos
Artrite Experimental , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Adjuvante de Freund/efeitos adversos , Indometacina/efeitos adversos , Sesquiterpenos Policíclicos , Ratos , Ratos Wistar , Compostos de Sulfidrila , Superóxido Dismutase/uso terapêutico , Fator de Necrose Tumoral alfa
3.
J Ethnopharmacol ; 292: 115173, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35314418

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Waltheria viscosissima A. St.- Hil (Malvaceae) is also known as 'Malva branca', has been reported as ethnopharmacologically useful plant containing antinociceptive and anti-inflammatory properties, but scientific evidence is absent. AIM OF THE STUDY: Elucidate the antinociceptive, anti-inflammatory and antioxidant activity of the crude ethanol extract (EEBWa.v) and alkaloid fraction (FAWa.v) of aerial parts of the W. viscosissima in healthy mice with induced inflammation. MATERIALS AND METHODS: EEBWa.v and FAWa.v (50, 100 and 200 mg/kg) and morphine (10 mg/kg) were used in vivo tests of chemical nociception induced by acetic acid (0.6%; 10 mg/kg) and formalin (2.5%) in Swiss male mice. Acute inflammation was induced by carrageenan (1%) in vivo tests and there were several groups tested. The control (inflammation induced without treatment) and the groups treated with EEBWa.v (100 mg/kg), FAWa.v (100 mg/kg) and dexamethasone (2 mg/kg). After this procedure, the animals were euthanized and the peritoneal fluid was collected to evaluate cell migration and redox balance (malondialdehyde - MDA and Total Antioxidant Capacity - TAC). RESULTS: The morphine, EEBWa.v (50 and 100 mg/kg) and FAWa.v (100 mg/kg) significantly reduced the number of abdominal writhes compared to the control group. FAWa.v (100 mg/kg) was superior to FAWa.v (200 mg/kg). In the formalin-induced nociception model (neurogenic phase) EEBWa.v (50 and 200 mg/kg) significantly reduced the number of paw licks. In the inflammatory phase with peripheral action, FAWa.v (100 mg/kg) was superior to EEBWa.v (200 mg/kg). EEBWa.v and FAWa.v (100 mg/kg) proved to be significant for the next experiments. Both samples showed reduction in cell migration, as well as those treated with dexamethasone, in animals with inflammation induced by carrageenan, compared to the untreated group. The redox balance (TAC and MDA) revealed that only EEBWa.v (100 mg/kg) had higher antioxidant potential than the untreated group and the dexamethasone group, p < 0.005 and p < 0.001, respectively. FAWa.v (100 mg/kg) did not show antioxidant activity superior to EEBWa.v. It was also detected that EEBWa.v and FAWa.v (100 mg/kg) failed to inhibit lipid peroxidation. CONCLUSIONS: The W. viscosissima stimulates pain control, which can be mediated by both central and peripheral action. These bioactive compounds showed promising and potential to replace standard medicines. This bioactive effect is statistically similar to morphine and dexamethasone, standard medicines on the market, but with the advantage of antioxidant activity.


Assuntos
Alcaloides , Malvaceae , Alcaloides/uso terapêutico , Analgésicos/efeitos adversos , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Carragenina , Dexametasona/uso terapêutico , Edema/tratamento farmacológico , Etanol/química , Formaldeído , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Morfina/farmacologia , Morfina/uso terapêutico , Dor/induzido quimicamente , Dor/tratamento farmacológico , Extratos Vegetais/efeitos adversos
4.
Oxid Med Cell Longev ; 2022: 6025900, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154569

RESUMO

The use of phytochemicals is gaining interest for the treatment of metabolic syndromes over the synthetic formulation of drugs. Senna is evolving as one of the important plants which have been vastly studied for its beneficial effects. Various parts of Senna species including the root, stem, leaves, and flower are found rich in numerous phytochemicals. In vitro, in vivo, and clinical experiments established that extracts from Senna plants have diverse beneficial effects by acting as a strong antioxidant and antimicrobial agent. In this review, Senna genus is comprehensively discussed in terms of its botanical characteristics, traditional use, geographic presence, and phytochemical profile. The bioactive compound richness contributes to the biological activity of Senna plant extracts. The review emphasizes on the in vivo and in vitro antioxidant and anti-infectious properties of the Senna plant. Preclinical studies confirmed the beneficial effects of the Senna plant extracts and its bioactive components in regard to the health-promoting activities. The safety, side effects, and therapeutic limitations of the Senna plant are also discussed in this review. Additional research is necessary to utilize the phenolic compounds towards its use as an alternative to pharmacological treatments and even as an ingredient in functional foods.


Assuntos
Anti-Infecciosos/efeitos adversos , Antioxidantes/efeitos adversos , Compostos Fitoquímicos/efeitos adversos , Extratos Vegetais/efeitos adversos , Plantas Medicinais/química , Senna (Planta)/química , Animais , Etnofarmacologia/métodos , Humanos , Medicina Tradicional/efeitos adversos , Fitoterapia/efeitos adversos , Componentes Aéreos da Planta/química , Raízes de Plantas/química
5.
Chem Res Toxicol ; 35(2): 140-162, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35045245

RESUMO

The cost-effectiveness of presently used therapies is a problem in overall redox-based management, which is posing a significant financial burden on communities across the world. As a result, sophisticated treatment models that provide notions of predictive diagnoses followed by targeted preventive therapies adapted to individual patient profiles are gaining global acclaim as being beneficial to patients, the healthcare sector, and society as a whole. In this context, natural flavonoids were considered due to their multifaceted antioxidant, anti-inflammatory, and anticancer effects as well as their low toxicity and ease of availability. The aim of this review is to focus on the capacity of flavonoids to modulate the responsiveness of various diseases and ailments associated with redox toxicity. The review will also focus on the flavonoids' pathway-based redox activity and the advancement of redox-based therapies as well as flavonoids' antioxidant characteristics and their influence on human health, therapeutics, and chemical safety. Research findings indicated that flavonoids significantly exhibit various redox-based therapeutic responses against several diseases such as inflammatory, neurodegenerative, cardiovascular, and hepatic diseases and various types of cancer by activating the Nrf2/Keap1 transcription system, suppressing the nuclear factor κB (NF-κB)/IκB kinase inflammatory pathway, abrogating the function of the Hsp90/Hsf1 complex, inhibiting the PTEN/PI3K/Akt pathway, and preventing mitochondrial dysfunction. Some flavonoids, especially genistein, apigenin, amentoflavone, baicalein, quercetin, licochalcone A, and biochanin A, play a potential role in redox regulation. Conclusions of this review on the antioxidant aspects of flavonoids highlight the medicinal and folk values of these compounds against oxidative stress and various diseases and ailments. In short, treatment with flavonoids could be a novel therapeutic invention in clinical trials, as we hope.


Assuntos
Anti-Inflamatórios/efeitos adversos , Antineoplásicos/efeitos adversos , Antioxidantes/efeitos adversos , Flavonoides/efeitos adversos , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Atenção à Saúde , Flavonoides/química , Flavonoides/metabolismo , Humanos , Estrutura Molecular , Oxirredução
6.
Eur J Pharmacol ; 914: 174615, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34863994

RESUMO

In this study, the therapeutic efficacy of quercetin in combination with remdesivir and favipiravir, were evaluated in severe hospitalized COVID-19 patients. Our main objective was to assess the ability of quercetin for preventing the progression of the disease into critical phase, and reducing the levels of inflammatory markers related to SARS-Cov-2 pathogenesis. Through an open-label clinical trial, 60 severe cases were randomly divided into control and intervention groups. During a 7-day period, patients in the control group received antivirals, i.e., remdesivir or favipiravir, while the intervention group was treated with 1000 mg of quercetin daily in addition to the antiviral drugs. According to the results, taking quercetin was significantly associated with partial earlier discharge and reduced serum levels of ALP, q-CRP, and LDH in the intervention group. Furthermore, although the values were in normal range, the statistical outputs showed significant increase in hemoglobin level and respiratory rate in patients who were taking quercetin. Based on our observations, quercetin is safe and effective in lowering the serum levels of ALP, q-CRP, and LDH as critical markers involved in COVID-19 severity. However, according to the non-significant borderline results in comparing the mortality, the ICU-admission rate, and the duration of ICU-admission, further studies can be helpful to compensate the limitations of our study and clarify the therapeutic potential of quercetin in COVID-19 treatments.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Amidas , COVID-19 , Pirazinas , Quercetina , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Amidas/administração & dosagem , Amidas/efeitos adversos , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/mortalidade , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Alta do Paciente/estatística & dados numéricos , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Quercetina/administração & dosagem , Quercetina/efeitos adversos , Taxa Respiratória/efeitos dos fármacos
7.
J Oncol Pharm Pract ; 28(4): 827-835, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33861657

RESUMO

BACKGROUND: Chemotherapeutic agents, with or without other drugs and radiation, may cause indirect or direct hepatotoxicity. Doxorubicin-induced hepatotoxicity (DIH) is a major health concern in cancer patients receiving this cytotoxic drug that is mostly resulted from the production of reactive oxygen species leading to transient or permanent liver damages. Silymarin, a flavonoid extracted from the Silybum marianum, exhibits antioxidant and anti-inflammatory activities. PURPOSE: This study aimed to investigate the clinical efficacy of systemic administration of silymarin in management of chemotherapy induced hepatotoxicity in patients with non-metastatic breast cancer who received doxorubicin/cyclophosphamide-paclitaxel (AC-T) regimen.Material: In this randomized, triple blind, placebo-controlled clinical trial, 30 patients who received AC-T who fulfilled the inclusion criteria were randomly allocated to silymarin (n = 15) or placebo (n = 15) groups to receive oral silymarin 140 mg three times a day or placebo tablets, respectively. Fatty liver severity was assessed by liver ultrasound imaging and FibroScan® and also measurement of liver function tests before and after the intervention. RESULTS: There was a non-significant trend toward more severe liver involvement in placebo group comparing to the silymarin group after intervention based on ultrasonography (p = 0.083). Besides, in silymarin group, hepatic involvement grade based on ultrasonography considerably reduced after intervention (p = 0.012). However, no difference was found between two groups based on FibroScan and liver function tests. CONCLUSION: Oral administration of silymarin could significantly reduce hepatotoxicity severity after 1 month of treatment in non-metastatic breast cancer patients treated with AC-T regimen.


Assuntos
Neoplasias da Mama , Doença Hepática Induzida por Substâncias e Drogas , Silimarina , Antioxidantes/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclofosfamida , Método Duplo-Cego , Doxorrubicina/efeitos adversos , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Silimarina/farmacologia , Silimarina/uso terapêutico
8.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34850960

RESUMO

Uric acid (UA) is the final oxidation product of purine metabolism. Hyperuricemia has been previously reported to contribute to vascular endothelial dysfunction and the development of cardiovascular diseases, metabolic syndrome and chronic kidney diseases. In addition, it has been reported that fibroblast growth factor 21 (FGF21) can exert regulatory effects on UA­induced lipid accumulation. Therefore, the present study aimed to investigate the possible role of FGF21 in HUVEC cell injury induced by UA. The study used UA to induce HUVEC cell injury, inhibited sirtuin 1 (Sirt1) expression using EX527 and overexpressed FGF21 by transfection. Subsequently, reverse transcription­quantitative PCR was performed to measure the mRNA expression levels of FGF21, Sirt1 and inflammatory cytokines TNF­α, IL­1ß and IL­6, whereas western blotting was performed to measure their corresponding protein expression levels including FGF21, Sirt1, NLR family pyrin domain containing 3, pro­caspase1, apoptosis­associated speck­like protein containing a CARD, activating transcription factor 4, C/EBP homologous protein and eukaryotic initiation factor 2. Furthermore, dichloro­dihydro­fluorescein diacetate staining was performed to measure intracellular reactive oxygen species (ROS) generation in HUVECs. The levels of ROS and nitric oxide were also quantified using commercial assay kits. The results demonstrated that overexpression of FGF21 significantly inhibited UA treatment­induced endoplasmic reticulum (ER) stress, inflammation and oxidative stress in HUVECs. Furthermore, overexpression of FGF21 significantly activated Sirt1. The sirt1 inhibitor, EX527, significantly abrogated the suppressive effects of FGF21 overexpression on ER stress, inflammation and oxidative stress in UA­stimulated HUVECs. To conclude, results of the present study suggested that FGF21 may attenuate UA­induced ER stress, inflammation and vascular endothelial cell dysfunction by activating Sirt1. Therefore, FGF21 may be a potential effective target for the future treatment of vascular endothelial cell dysfunction.


Assuntos
Estresse do Retículo Endoplasmático , Endotélio Vascular/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/metabolismo , Inflamação/prevenção & controle , Estresse Oxidativo , Sirtuína 1/metabolismo , Ácido Úrico/efeitos adversos , Antioxidantes/efeitos adversos , Apoptose , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Fatores de Crescimento de Fibroblastos/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuína 1/genética
9.
J Ethnopharmacol ; 282: 114596, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492319

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The African Continent harbours approximately 26 Croton species. Many Croton species are used in traditional medicine in southern Africa to treat a variety of ailments including malaria, tuberculosis, microbial infection and inflammation. Considering the high diversity of the genus Croton, the ethnopharmacological information available on southern African species is rather limited. Furthermore, the potential for novel anti-inflammatory drug scaffolds has not previously been investigated. AIM OF THE STUDY: The aim of the study was to evaluate the potential of four South African Croton species extracts (Croton gratissimus, Croton pseudopulchellus, Croton sylvaticus, and Croton steenkampianus) for anti-inflammatory activity targeting the TLR4 signalling pathway and to assess the potential risk for hepatotoxicity and genotoxicity using an in vitro cellomics approach. MATERIAL AND METHODS: Leaf extracts of C. gratissimus, C. pseudopulchellus, C. sylvaticus and C. steenkampianus were prepared using methanol and chloroform (1:1, v/v). The anti-inflammatory activity was determined using LPS induced nitric oxide production in RAW 264.7 macrophages, while the hepatotoxicity and genotoxicity was evaluated using multi-parameter end point analysis in C3A and Vero cells, respectively. Mitochondrial membrane potential, mitochondrial mass, oxidative stress, lysosomal content and lipid accumulation were used as markers to assess the risk for hepatotoxicity. RESULTS: All four species attenuated nitric oxide production with negligible cytotoxicity. However, C. gratissimus yielded the most favorable profile. Cell density was significantly reduced in both C3A and Vero cells with the C. gratissimus extract providing a suitable toxicity profile amenable to further high content analysis. While there was no meaningful effect on mitochondrial dynamics, a strong dose dependent increase in lipid content, paralleled by an expansion of the lysosomal compartment, identifies a potential risk for steatosis. Risk for genotoxicity was investigated using the micronucleus assay which revealed a dose dependent increase in micronuclei formation. Changes in nuclear morphology and cell ploidy further strengthens the associated risk for genotoxicity and suggests the extract from C. gratissimus may function as an aneugen. Collectively, the data demonstrates that although the selected species possess anti-inflammatory components, the risk for possible hepatotoxic and genotoxic side effects may negate their prospect towards further drug development.


Assuntos
Anti-Inflamatórios , Doença Hepática Induzida por Substâncias e Drogas , Croton , Testes de Mutagenicidade/métodos , Extratos Vegetais , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacologia , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Chlorocebus aethiops , Etnofarmacologia/métodos , Técnicas In Vitro/métodos , Medicina Tradicional Africana , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Folhas de Planta , Células RAW 264.7 , Medição de Risco/métodos , Células Vero
10.
Braz. J. Pharm. Sci. (Online) ; 58: e18965, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1364419

RESUMO

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.


Assuntos
Animais , Masculino , Ratos , Preparações Farmacêuticas , Malva/metabolismo , Neglecta , Terapêutica/instrumentação , Gentamicinas , Malvaceae/classificação , Creatinina/administração & dosagem , Dosagem/métodos , Antioxidantes/efeitos adversos
11.
Eur Rev Med Pharmacol Sci ; 25(23): 7449-7459, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34919247

RESUMO

OBJECTIVE: Currently, no NASH-specific therapies are approved by the US Food and Drug Administration. This study aimed to compare the clinical effect of vitamin E (Vit. E), Ursodeoxycholic Acid (UDCA) and pentoxifylline (PTX) on Egyptian patients with NASH with exploration of their possible roles on inflammatory cytokines and chemokines mainly Interleukin 6 (IL6) and Monocyte Chemoattractant Protein-1 (CCL2/MCP-1). PATIENTS AND METHODS: We conducted a 3-month, randomized, single-blind study in 102 Egyptian NASH patients who were divided into three groups; group 1 received Vit. E 400 mg twice a day, group 2 received UDCA 250 mg twice a day and group 3 received PTX 400 mg twice daily. Liver aminotransferases (AST, ALT), IL6, CCL2/MCP-1, albumin, bilirubin, and lipid panel were measured both before and after intervention intake. RESULTS: A significant decrease was found in liver aminotransferases, serum cytokine and chemokine in participants after Vit. E, UDCA or PTX intake. Compared to the UDCA and PTX groups, liver aminotransferases, serum cytokine and chemokine showed a more statistically significant reduction after Vit. E administration (50%, 43%, 57% and 55% for ALT, AST, IL6 and CCL2/MCP-1, respectively). In contrast, other biochemical tests showed non-significant change after any drug intake. None of the tested drugs showed significant safety issues in this population. CONCLUSIONS: Treatment with Vit. E, UDCA and PTX was both safe and effective in improving hepatic aminotransferases and inflammatory markers in Egyptian NASH patients. The superior effect of Vit. E compared to UDCA and PTX may suggest that oxidative stress plays a key role in disease progression of NASH patients. Moreover, IL6 and CCL2/MCP-1 may be used with or without ALT for treatment evaluation of NASH people.


Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Pentoxifilina/uso terapêutico , Ácido Ursodesoxicólico/uso terapêutico , Vitamina E/uso terapêutico , Adulto , Antioxidantes/efeitos adversos , Antioxidantes/uso terapêutico , Colagogos e Coleréticos/efeitos adversos , Colagogos e Coleréticos/uso terapêutico , Progressão da Doença , Egito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Pentoxifilina/efeitos adversos , Inibidores de Fosfodiesterase/efeitos adversos , Inibidores de Fosfodiesterase/uso terapêutico , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Ácido Ursodesoxicólico/efeitos adversos , Vitamina E/efeitos adversos
12.
J Diabetes Res ; 2021: 1010268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926696

RESUMO

Diabetic nephropathy (DN) is a progressive microvascular diabetic complication. Growing evidence shows that persistent mitochondrial dysfunction contributes to the progression of renal diseases, including DN, as it alters mitochondrial homeostasis and, in turn, affects normal kidney function. Pharmacological regulation of mitochondrial networking is a promising therapeutic strategy for preventing and restoring renal function in DN. In this review, we have surveyed recent advances in elucidating the mitochondrial networking and signaling pathways in physiological and pathological contexts. Additionally, we have considered the contributions of nontraditional therapy that ameliorate mitochondrial dysfunction and discussed their molecular mechanism, highlighting the potential value of nontraditional therapies, such as herbal medicine and lifestyle interventions, in therapeutic interventions for DN. The generation of new insights using mitochondrial networking will facilitate further investigations on nontraditional therapies for DN.


Assuntos
Antioxidantes/uso terapêutico , Nefropatias Diabéticas/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Rim/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Comportamento de Redução do Risco , Animais , Antioxidantes/efeitos adversos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Rim/metabolismo , Rim/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Resultado do Tratamento
13.
Toxins (Basel) ; 13(11)2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34822553

RESUMO

Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = -3.52, 95% confidence interval = -5.63 to -1.41, p = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, p = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease.


Assuntos
Antioxidantes/efeitos adversos , Prurido/tratamento farmacológico , Tiossulfatos/efeitos adversos , Uremia/tratamento farmacológico , Vasodilatadores/efeitos adversos , Antioxidantes/farmacologia , Humanos , Prurido/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiossulfatos/farmacologia , Uremia/complicações , Vasodilatadores/farmacologia
14.
Oxid Med Cell Longev ; 2021: 5577541, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707777

RESUMO

Mitochondrial dysfunction and oxidative stress are extensively linked to Parkinson's disease (PD) pathogenesis. Melatonin is a pleiotropic molecule with antioxidant and neuroprotective effects. The aim of this study was to evaluate the effect of melatonin on oxidative stress markers, mitochondrial complex 1 activity, and mitochondrial respiratory control ratio in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial study was conducted in 26 patients who received either 25 mg of melatonin or placebo at noon and 30 min before bedtime for three months. At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.


Assuntos
Antioxidantes/uso terapêutico , Antiparkinsonianos/uso terapêutico , Melatonina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Antioxidantes/efeitos adversos , Antiparkinsonianos/efeitos adversos , Biomarcadores/sangue , Respiração Celular/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Complexo I de Transporte de Elétrons/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Melatonina/efeitos adversos , México , Mitocôndrias/metabolismo , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Fatores de Tempo , Resultado do Tratamento
15.
Biomed Pharmacother ; 144: 112328, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34653753

RESUMO

Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.


Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cisplatino/efeitos adversos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Anti-Infecciosos/uso terapêutico , Antioxidantes/efeitos adversos , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Humanos , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Extratos Vegetais/efeitos adversos
16.
Biomed Pharmacother ; 142: 112004, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34388527

RESUMO

The pharmacological characteristics of phytochemicals have prompted a lot of interest in their application in disease management. Due to the high incidence of cancer related mortality and morbidity throughout the world; experiments have concentrated on identifying the anticancer potential of natural substances. Many phytochemicals such as flavonoids and their derivatives produced from food offer a variety of new anti-cancer agents which prevent the cancer progression. Taxifolin, a unique bioactive flavonoid, is a dietary component that has grabbed the interest of dietitians and medicinal chemists due to its wide range of health benefits. It is a powerful antioxidant with a well-documented effect in the prevention of several malignancies in humans. Taxifolin has shown promising inhibitory activity against inflammation, malignancies, microbial infection, oxidative stress, cardiovascular disease, and liver disease. Anti-cancer activity has been shown to be relatively significant than other activities investigated in vitro and in vivo with a little or no side effects to the normal healthy cells. In summary this review offers the synopsis of recent breakthroughs in the use of taxifolin as a cancer treatment, as well as mechanisms of action. However, to develop a medicine for human usage, more study on pharmacokinetic profile, profound molecular mechanisms, and drug safety criteria should be conducted utilizing well-designed randomized clinical trials.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Quercetina/análogos & derivados , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/efeitos adversos , Antioxidantes/isolamento & purificação , Humanos , Neoplasias/tratamento farmacológico , Quercetina/efeitos adversos , Quercetina/isolamento & purificação , Quercetina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443483

RESUMO

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Compostos Fitoquímicos/farmacologia , Polifenóis/farmacologia , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antioxidantes/efeitos adversos , Antioxidantes/química , Antioxidantes/uso terapêutico , Humanos , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Polifenóis/efeitos adversos , Polifenóis/química , Polifenóis/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
18.
Mol Biol Rep ; 48(9): 6539-6550, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34420148

RESUMO

Lipoic acid (LA) is globally known and its supplements are widely used. Despite its importance for the organism it is not considered a vitamin any more. The multiple metabolic forms and the differences in kinetics (absorption, distribution and excretion), as well as the actions of its enantiomers are analysed in the present article together with its biosynthetic path. The proteins involved in the transfer, biotransformation and activity of LA are mentioned. Furthermore, the safety and the toxicological profile of the compound are commented, together with its stability issues. Mechanisms of lipoic acid intervention in the human body are analysed considering the antioxidant and non-antioxidant characteristics of the compound. The chelating properties, the regenerative ability of other antioxidants, the co-enzyme activity and the signal transduction by the implication in various pathways will be discussed in order to be elucidated the pleiotropic effects of LA. Finally, lipoic acid integrating analogues are mentioned under the scope of the multiple pharmacological actions they acquire towards degenerative conditions.


Assuntos
Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Antipsicóticos/metabolismo , Quelantes/metabolismo , Hipnóticos e Sedativos/metabolismo , Hipoglicemiantes/metabolismo , Ácido Tióctico/análogos & derivados , Ácido Tióctico/metabolismo , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/química , Antioxidantes/efeitos adversos , Antioxidantes/química , Antipsicóticos/efeitos adversos , Antipsicóticos/química , Quelantes/efeitos adversos , Quelantes/química , Suplementos Nutricionais , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/química , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/química , /química , Cinética , Oxirredução , Transdução de Sinais , Ácido Tióctico/efeitos adversos , Ácido Tióctico/química
19.
BMC Pulm Med ; 21(1): 268, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404358

RESUMO

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .


Assuntos
Asma , COVID-19 , Curcumina , Eosinófilos , Imunoglobulina E/sangue , Administração Oral , Adulto , Assistência Ambulatorial/métodos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Asma/sangue , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/fisiopatologia , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Ensaios Clínicos Fase II como Assunto , Curcumina/administração & dosagem , Curcumina/efeitos adversos , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Contagem de Leucócitos/métodos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
20.
Oxid Med Cell Longev ; 2021: 3617042, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34373764

RESUMO

Since its discovery in 1905 and its employment in everyday medical practice as a local anesthetic, to its highly controversial endorsement as an "anti-aging" molecule in the sixties and seventies, procaine is part of the history of medicine and gerontoprophylaxis. Procaine can be considered a "veteran" drug due to its long-time use in clinical practice, but is also a molecule which continues to incite interest, revealing new biological and pharmacological effects within novel experimental approaches. Therefore, this review is aimed at exploring and systematizing recent data on the biochemical, cellular, and molecular mechanisms involved in the antioxidant and potential geroprotective effects of procaine, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature within the last 30 years, describing the positive, as well as the negative reports; (2) the experimental data supporting the beneficial effects of procaine in preventing or alleviating age-related pathology; and (3) the multifactorial pathways procaine impacts oxidative stress, inflammation, atherogenesis, cerebral age-related pathology, DNA damage, and methylation. According to reviewed data, procaine displayed antioxidant and cytoprotective actions in experimental models of myocardial ischemia/reperfusion injury, lipoprotein oxidation, endothelial-dependent vasorelaxation, inflammation, sepsis, intoxication, ionizing irradiation, cancer, and neurodegeneration. This analysis painted a complex pharmacological profile of procaine: a molecule that has not yet fully expressed its therapeutic potential in the treatment and prevention of aging-associated diseases. The numerous recent reports found demonstrate the rising interest in researching the multiple actions of procaine regulating key processes involved in cellular senescence. Its beneficial effects on cell/tissue functions and metabolism could designate procaine as a valuable candidate for the well-established Geroprotectors database.


Assuntos
Envelhecimento/efeitos dos fármacos , Anestésicos Locais/farmacologia , Antioxidantes/farmacologia , Procaína/farmacologia , Anestésicos Locais/efeitos adversos , Animais , Antioxidantes/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Humanos , Procaína/efeitos adversos
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