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1.
Eur J Endocrinol ; 184(3): 423-429, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33621192

RESUMO

Context: Colonic polyps occur in 30-40% of acromegalic patients, increasing the risk of colon carcinoma. Although debated, there is emerging evidence that metformin may play a protective role in diabetic and non-diabetic patients with colonic polyps and its use in chemoprevention is currently explored. Objective: Evaluate the prevalence of colonic polyps in acromegalic patients treated or not with metformin and explore its possible protective role. Design: Exploratory cross-sectional study in two tertiary Italian referral centres. Met: hods: Out of 153 acromegalic patients, we selected 58 patients (36-82 years; f: 33) who had at least one colonoscopy performed within the first 2 years of diagnosis. Presence of colonic polyps/cancer and related risk factors, current metformin and acetylsalicylic acid intake, disease duration, therapies for acromegaly, hormonal and metabolic parameters were assessed. Results: An overall prevalence of 36% polyps was found. Based on the presence of polyps, we identified two groups, comparable for age, BMI, disease duration, glucose, insulin, HOMA-IR, HbA1c, GH and IGF-I levels. Of the patients with polyps (including three adenocarcinomas) only 24% were treated with metformin vs 57% of patients without polyps. Multivariate analysis confirmed a significant negative association between colonic polyps and metformin intake (OR: 0.22, 95% CI: 0.06-0.77, P = 0.01), whereas no significant association was found between polyps and age (P = 0.10), overweight/obesity (P = 0.54), smoking (P = 0.15), acetylsalicylic acid intake (P = 0.99), disease duration (P = 0.96), somatostatin analogues treatment (P = 0.70). Conclusions: These findings, though deriving from an exploratory study, could suggest a protective role of metformin on the development of colonic polyps in acromegaly, and need to be confirmed in an extended study population.


Assuntos
Acromegalia/complicações , Pólipos do Colo/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Pólipos do Colo/epidemiologia , Pólipos do Colo/etiologia , Colonoscopia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Risco
3.
J Assoc Physicians India ; 69(2): 25-29, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527807

RESUMO

Achieving adequate glycemic control in type 2 diabetes mellitus (T2DM) remains a difficult but achievable goal. Oral agents (OADs) are important option for management of T2DM. Most T2DM patients require more than one medication for adequate glycemic control. Metformin based combination therapy is recommended when monotherapy is insufficient. Evogliptin is a recently developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which can to be combined with metformin for treating T2DM. Combination therapy of Evogliptin and Metformin lowers blood glucose via augmentation of insulin secretion, suppression of glucagon secretion, and insulin sensitization. Co-administration of Evogliptin and Metformin showed no clinically relevant pharmacokinetic differences compared to the administration of each drug alone. Combination therapy of Evogliptin and Metformin also provides significantly better glycemic control compared to the respective monotherapies. Efficacy and safety of Evogliptin and Metformin had been demonstrated in several multicentre randomized clinical trials conducted in various countries like South Korea, Russia and India. Consequently, fixed dose combination (FDC) of Evogliptin and Metformin is approved in South Korea and India. Complexity of the treatment regimen and polypharmacy are well-known factors of poor medication adherence and FDCs have the potential to improve adherence by reducing the pill burden. Adoption of this combination therapy in clinical practice for management of T2DMs will provide a greater degree of HbA1c reduction than that observed with the use of either drug as monotherapy, and is unlikely to cause significant hypoglycemia. Combination therapy of Evogliptin and Metformin is a promising strategy in the treatment of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Quimioterapia Combinada , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/uso terapêutico , Índia , Metformina/uso terapêutico , Piperazinas , Federação Russa
4.
Ecotoxicol Environ Saf ; 208: 111623, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396143

RESUMO

Monitoring the consumption of pharmaceuticals and licit drugs is important for assessing the needs of public health owing to the impact on individuals as well as society. The present work applied wastewater-based epidemiology to profile the spatial patterns of metformin, nicotine, and caffeine use and their correlations. Influent wastewater samples were collected from 27 wastewater treatment plants in 22 typical Chinese cities that covered all geographic regions of the country. The consumption of metformin ranged from 0.02 g/d/1000 inh to 8.92 g/d/1000 inh, whereas caffeine and nicotine consumption ranged from 4.33 g/d/1000 inh to 394 g/d/1000 inh and 0.17 g/d/1000 inh to 1.88 g/d/1000 inh, respectively. There were significant regional differences in the consumption of caffeine, with the highest consumption in East China and the lowest consumption in Northeast China. The consumption and concentration of caffeine were related to the gross domestic product and per capita disposable income of urban residents, respectively. There was a correlation between the concentrations of caffeine and cotinine (a nicotine metabolite), thereby indicating that individuals that use one of these substances are likely to use the other substance. A significant relationship was found between the concentration of metformin and cotinine, thereby implying that the use of tobacco may be correlated with type 2 diabetes. Co-analysis of these substances in wastewater may provide a more accurate picture of substance use situations within different communities and provide more information on human health, human behavior, and the economy. This report describes the newest study related to the consumption of metformin among the general population in China.


Assuntos
Cafeína/análise , Metformina/análise , Nicotina/análise , Uso de Tabaco/epidemiologia , Águas Residuárias/química , Vigilância Epidemiológica Baseada em Águas Residuárias , Cafeína/química , China/epidemiologia , Cidades , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Nicotina/química , Análise Espacial , Tabaco , Águas Residuárias/análise
5.
Anticancer Res ; 41(2): 821-828, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517287

RESUMO

BACKGROUND/AIM: Preclinical studies on metformin use and endometrial cancer have been promising but epidemiological studies have reported variable results. This study aimed to assess if metformin use is associated with endometrial cancer aggressiveness and survival in women with type 2 diabetes (T2D). PATIENTS AND METHODS: This retrospective hospital-based cohort consisted of women with T2D who were treated for endometrial cancer at the Oulu University Hospital, Finland, between 2007 and 2014. RESULTS: The sample size was 121 patients: 58 metformin users and 63 metformin non-users. Intriguingly, type 2 histology, deep myometrial invasion and the presence of lymphovascular invasion were more common in the metformin user group. However, metformin use showed no association with overall survival and progression-free survival. CONCLUSION: Metformin use was associated with poorer prognostic factors in endometrial cancer patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Neoplasias do Endométrio/patologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/mortalidade , Feminino , Finlândia , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
6.
Nat Commun ; 12(1): 440, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469052

RESUMO

The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8+ T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8+ T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Micropartículas Derivadas de Células/imunologia , Portadores de Fármacos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , /uso terapêutico , Memória Imunológica , Masculino , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Células RAW 264.7 , Evasão Tumoral/efeitos dos fármacos , Evasão Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , /imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Med Case Rep ; 15(1): 17, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33472652

RESUMO

BACKGROUND: Metformin-associated lactic acidosis (MALA) is a widely documented adverse event of metformin. Despite being considered one of the main causes of metabolic acidosis, the association between an anion gap and MALA diagnosis is still uncertain. CASE PRESENTATION: Cases involving six Caucasian patients with suspected MALA who were admitted to the emergency department were analysed. All these patients presented with pH values < 7.35, lactate levels > 2 mmol/L, and estimated glomerular filtration < 30 mL/min. Metformin plasma concentrations were > 2.5 mg/L in all the patients. The highest metformin concentrations were not found in the patients with the highest lactate levels. The anion gap values ranged from 12.3 to 39.3, with only two patients exhibiting values > 14. CONCLUSIONS: In patients with MALA, there is a significant variability in the anion gap values, which is not related to the level of metformin accumulation, and therefore, it is doubtful whether measuring anion gaps is useful as an approach for MALA diagnosis.


Assuntos
Equilíbrio Ácido-Base , Acidose Láctica/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Acidose Láctica/sangue , Acidose Láctica/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Ânions/sangue , Cátions/sangue , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Metformina/sangue , Pessoa de Meia-Idade
8.
Viruses ; 13(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440724

RESUMO

Enteric symptomology seen in early-stage severe acute respiratory syndrome (SARS)-2003 and COVID-19 is evidence of virus replication occurring in the intestine, liver and pancreas. Aberrant lipid metabolism in morbidly obese individuals adversely affects the COVID-19 immune response and increases disease severity. Such observations are in line with the importance of lipid metabolism in COVID-19, and point to the gut as a site for intervention as well as a therapeutic target in treating the disease. Formation of complex lipid membranes and palmitoylation of coronavirus proteins are essential during viral replication and assembly. Inhibition of fatty acid synthase (FASN) and restoration of lipid catabolism by activation of AMP-activated protein kinase (AMPK) impede replication of coronaviruses closely related to SARS-coronavirus-2 (CoV-2). In vitro findings and clinical data reveal that the FASN inhibitor, orlistat, and the AMPK activator, metformin, may inhibit coronavirus replication and reduce systemic inflammation to restore immune homeostasis. Such observations, along with the known mechanisms of action for these types of drugs, suggest that targeting fatty acid lipid metabolism could directly inhibit virus replication while positively impacting the patient's response to COVID-19.


Assuntos
/metabolismo , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos , /fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico , /virologia , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/virologia , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/metabolismo , Humanos , Metformina/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/virologia , Orlistate/uso terapêutico , Proteínas Virais/metabolismo , Montagem de Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
9.
J Cell Mol Med ; 25(4): 2279-2284, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421348

RESUMO

Obesity increases the morbidity and severity of asthma, with poor sensitivity to corticosteroid treatment. Metformin has potential effects on improving asthma airway inflammation. Regulatory T cells (Tregs) play a key role in suppressing the immunoreaction to allergens. We built an obese asthmatic mouse model by administering a high-fat diet (HFD) and ovalbumin (OVA) sensitization, with daily metformin treatment. We measured the body weight and airway inflammatory status by histological analysis, qRT-PCR, and ELISA. The percentage of Tregs was measured by flow cytometry. Obese asthmatic mice displayed more severe airway inflammation and more significant changes in inflammatory cytokines. Metformin reversed the obese situation and alleviated the airway inflammation and remodelling with increased Tregs and related transcript factors. The anti-inflammatory function of metformin may be mediated by increasing Tregs.


Assuntos
Anti-Inflamatórios/farmacologia , Asma/tratamento farmacológico , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Obesidade/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Asma/imunologia , Asma/patologia , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Linfócito CD4 , Dieta Hiperlipídica , Modelos Animais de Doenças , Humanos , Inflamação , Interleucina-4/antagonistas & inibidores , Interleucina-4/imunologia , Interleucina-4/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos , Obesidade/imunologia , Obesidade/patologia , Ovalbumina/administração & dosagem , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Linfócitos T Reguladores/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Rev Med Suisse ; 17(723): 188-191, 2021 Jan 27.
Artigo em Francês | MEDLINE | ID: mdl-33507658

RESUMO

Diabetes is a rapidly evolving discipline, numerous new molecules and recommendations are available. However, these rapid changes are sometimes difficult to follow for general practitioners. Metformin remains the cornerstone of type 2 diabetes treatment after lifestyle modifications, which should always be encouraged before medications. Currently, the best classes to add after metformin seem to be SGLT2 inhibitors and GLP-1 receptor agonists, as these molecules showed some cardiovascular and renal beneficial effects in dedicated studies. Nevertheless, the current pharmacological plethora is paradoxically associated with clinical inertia as general practitioners may be in trouble finding the right medication. This article will highlight novelties in the field of diabetes during the year 2020.


Assuntos
Diabetes Mellitus Tipo 2 , Clínicos Gerais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipoglicemiantes/uso terapêutico , Metformina , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
11.
Medicine (Baltimore) ; 100(1): e23954, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429755

RESUMO

BACKGROUND: The incidence of gestational diabetes is increasing, which not only cause adverse pregnancy outcomes, but also increases the risk of diabetes for pregnant women and their children. Insulin is the gold standard for the treatment of gestational diabetes, but there are some disadvantages, such as poor patient compliance. Metformin has been used in the treatment of gestational diabetes, but the evaluation of its efficacy and safety is lack of reliable evidence-based medicine evidence. The purpose of this study was to systematically investigate the efficacy and safety of metformin in the treatment of diabetic gestational diabetes. METHODS: Computer searches China National Knowledge Infrastructure, Wanfang, Vipu Information Chinese Journal Service Platform and China Biomedical Database, PubMed, Embase, Web of Science, the Cochrane Library from the establishment of the database to November 2020, randomized controlled clinical trials of metformin in the treatment of gestational diabetes mellitus were conducted in English and Chinese. Two researchers independently carried out data extraction and literature quality evaluation on the quality of the included study, and the included literature was analyzed by Meta using RevMan5.3 software. RESULTS: In this study, the efficacy and safety of metformin in the treatment of diabetic gestational diabetes were investigated by evaluating the outcome indicators of pregnant women and newborn babies respectively. CONCLUSION: This study will provide reliable evidence for the clinical application of metformin in the treatment of diabetic gestational diabetes. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/ OSF.IO / 7RB95.


Assuntos
Protocolos Clínicos , Diabetes Gestacional/tratamento farmacológico , Metformina/normas , Adulto , Feminino , Humanos , Hipoglicemiantes/normas , Hipoglicemiantes/uso terapêutico , Metanálise como Assunto , Metformina/uso terapêutico , Gravidez , Revisões Sistemáticas como Assunto
12.
Adv Exp Med Biol ; 1307: 417-440, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32424494

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease globally. NAFLD patients can have a progressive phenotype, non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis, liver failure and cancer. There is a close bi-directional relationship between NAFLD and type 2 diabetes mellitus (T2DM); NAFLD increases the risk for T2DM and its complications whereas T2DM increases the severity of NAFLD and its complications. The large global impact of NAFLD and T2DM on healthcare systems requires a paradigm shift from specialty care to early identification and risk stratification of NAFLD in primary care and diabetes clinics. Approach to diagnosis, risk stratification and management of NAFLD is discussed. In addition to optimizing the control of coexisting cardiometabolic comorbidities, early referral of NAFLD patients at high risk of having NASH or significant fibrosis to hepatology specialist care may improve management and allow access for clinical trials. Lifestyle modifications, vitamin E, pioglitazone and metformin are currently available options that may benefit patients with T2DM and NAFLD. The burst of clinical trials investigating newer therapeutic agents for NAFLD and NASH offer hope for new, effective and safe therapies in the near future.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Cirrose Hepática , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia
13.
Adv Exp Med Biol ; 1307: 257-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32548833

RESUMO

Once a woman is diagnosed with gestational diabetes mellitus (GDM), two strategies are considered for management; life-style modifications and pharmacological therapy. The management of GDM aims to maintain a normoglycemic state and to prevent excessive weight gain in order to reduce maternal and fetal complications. Lifestyle modifications include nutritional therapy and exercise. Calorie restriction with a low glycemic index diet is recommended to avoid postprandial hyperglycemia and to reduce insulin resistance. Blood glucose levels, HbA1c levels, and ketonuria are monitored to analyze the efficacy of conservative management. Pharmacological treatment is initiated if conservative strategies fail to provide expected glucose levels during follow-ups.Insulin has been the first choice for the treatment of diabetes during pregnancy. Recently, metformin has been used more commonly in diabetic pregnant women in cases when insulin cannot be prescribed, after its safety has been proven. However, a high percentage of women, which may be up to 46% may require additional insulin to maintain expected blood glucose levels. The evidence on the long-term safety of other oral anti-diabetics has been lacking yet.Women with diet-controlled GDM can wait for spontaneous labor expectantly in case there are no obstetric indications for birth. However, in women with GDM under insulin therapy or with poor glycemic control, elective induction at term is recommended by authorities.The women who have GDM during pregnancy should be counseled about their increased risks of impaired glucose tolerance, type 2 diabetes mellitus, hypertensive disorders, cardiovascular diseases, and metabolic syndrome.


Assuntos
Diabetes Gestacional , Hipoglicemiantes/uso terapêutico , Glicemia , Diabetes Mellitus Tipo 2 , Diabetes Gestacional/tratamento farmacológico , Feminino , Humanos , Insulina/uso terapêutico , Metformina/uso terapêutico , Gravidez , Fatores de Risco
14.
Sci Total Environ ; 751: 142302, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33181992

RESUMO

The objective of this study was to investigate the photocatalytic removal of PPCPs using poly(3,4-ethylenedioxythiophene) (PEDOT) polymer. PEDOT is a conducting polymer that exhibits excellent photocatalytic activity and was used in this study without any additives or metal co-catalysts. The PEDOT was synthesized using chemical oxidative polymerization and characterized further for composition and morphology. PEDOT, in the presence of UV irradiation, showed >99% degradation of one of the most widely prescribed antidiabetic drugs, metformin, within 60 min. The effect of varying concentration of PEDOT, pH, and light irradiance was studied to achieve maximum photocatalytic efficiency. Two major degradation products of metformin of m/z 116 and 126 were detected using triple quadrupole LC-MS/MS, while the degradation kinetics was found to be of pseudo-first-order. Results revealed that photogenerated electrons, holes, and radical species played a role in the PPCPs' degradation. When a mixture of seven PPCPs in the ultra-pure water matrix was tested, more than 99% removal was observed for most of the PPCPs within 60 min. The removal efficiency decreased in a real wastewater effluent due to the presence of dissolved organic matter; however, still, more than 50% removal was observed for majority of the studied PPCPs. The results of PEDOT reusability revealed that the reuse contributed to the drop in the conductivity and subsequent drop in the photocatalytic activity; however, a simple acid treatment was found to be effective to recoup its conductivity. PEDOT was successfully immobilized on an electrospun fiber mat to enhance its applicability.


Assuntos
Metformina , Poluentes Químicos da Água , Compostos Bicíclicos Heterocíclicos com Pontes , Cromatografia Líquida , Polímeros , Espectrometria de Massas em Tandem , Água , Poluentes Químicos da Água/análise
15.
Sci Total Environ ; 750: 141685, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32862004

RESUMO

Human exposure to bisphenol A (BPA) is unavoidable in daily life. Recently, research has showen that BPA could induce oxidative imbalance, thereby causing reproductive toxicity and liver dysfunction. Accumulated evidence has demonstrated that metformin possesses strong anti-oxidative properties. This study aimed to study the mechanism underlying the hepatic-protective effect of metformin on liver injury induced by BPA in rats via the UPLC-MS/MS metabolomics approach. Forty-two male rats were randomly divided into six groups (n = 7), namely the saline group (control), the corn oil group (vehicle), the metformin group (Met), the bisphenol A group (BPA), the bisphenol A and metformin group (BPA + Met), and the bisphenol A and diammonium glycyrrhizinate (positive control) group (BPA + DG). Serum was collected for biochemical analysis and metabolomics, and liver tissue was collected for histopathology and metabolomics in each group. We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA. On the other hand, metformin could significantly enhance the total antioxidant capacity in BPA rats. Notably, metabolomics data indicated that the principal altered metabolic pathways based on the 26 differential metabolites in liver tissue, and 21 in serum among vehicle, BPA and BPA + Met groups, respectively, including cysteine and methionine metabolism, glutathione metabolism, and arginine biosynthesis and purine metabolism. Additionally, metformin significantly increased cystathionine ß synthase (CBS) and cystathionine γ lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats. Overall, this study's results provided new insights into the role and mechanism of metformin in BPA-induced liver injury in rats.


Assuntos
Cistationina gama-Liase , Metformina , Animais , Compostos Benzidrílicos/toxicidade , Cromatografia Líquida , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Humanos , Fígado/metabolismo , Masculino , Metformina/toxicidade , Fenóis , Ratos , Espectrometria de Massas em Tandem , Regulação para Cima
16.
Exp Gerontol ; 145: 111197, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33310152

RESUMO

Senior individuals are more susceptible to the irreversible outcomes of endothelial barrier dysfunction, the hallmark of Acute Respiratory Distress Syndrome (ARDS). The Severe Acute Respiratory Syndrome Coronovirus 2 (SARS-CoV-2) - inflicted ARDS delivers the devastating outcomes of the COVID-19 worldwide. Endothelial hyperpermeability has been associated with both the progression and establishment of the COVID-19 - related respiratory failure. In the present study we investigated the in vitro effects of Metformin in the permeability of bovine pulmonary artery endothelial cells. Our preliminary results suggest that moderate doses (0.1, 0.5, 1.0 mM) of this anti-diabetic agent enhance the vascular barrier integrity, since it produces an increase in the transendothelial resistance of endothelial monolayers. Thus, we speculate that Metformin may deliver a new therapeutic possibility in ARDS, alone or in combination with other barrier enhancers.


Assuntos
Metformina/uso terapêutico , /tratamento farmacológico , Animais , Bovinos , Células Endoteliais/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos
17.
J Ethnopharmacol ; 265: 113210, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32795501

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: One of the commonly prescribed 'anti-diabetic' polyherbal mixtures by European herbalists is made of Rubus fruticosus and Vaccinium myrtillus leaves, Potentilla erecta roots, Geum urbanum aerial parts and Phaseolus vulgaris pods. AIM OF THE STUDY: This study aimed to evaluate the phytochemical composition, antioxidant capacity, potential toxicity, hypoglycemic, hypolipidemic, nephroprotective and hepatoprotective activities of this polyherbal mixture decoction. MATERIALS AND METHODS: The phytochemical composition was evaluated using HPLC-UV. The antioxidant activity was assessed using the DPPH test. Potential toxicity was evaluated using the acute and sub-chronic oral toxicity method. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate (150 mg/kg). The animals whose blood glucose was >20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, D-10 and D-20 groups were treated with the polyherbal mixture (10 and 20 g of dry plant material/kg, respectively). I and M were control groups treated with insulin glargine (13 IU/kg) and metformin (150 mg/kg), respectively. Healthy control (HC) and diabetic control (DC) groups were treated with water. The blood glucose level was measured on days 14, 21 and 28. Lipid profile analysis was done on day 28. Pancreas, kidney and liver histopathology was evaluated using the H&E and Masson's trichrome staining. The liver tissue was additionally tested for PAS-positive cells. RESULTS: The HPLC-UV analysis revealed the presence of quinic, gallic and caftaric acid, arbutin, rutin, trifolin, astragalin, hyperoside, isoquercetin and quercitrin. The antioxidant activity of the extract was higher than the reference's one (p < 0.01). Treatment with the polyherbal mixture (10 and 20 g/kg) has shown no toxic effects. No major decline in blood sugar was recorded in I and M groups compared to the DC one (22.86 ±â€¯2.58, 28.5 ±â€¯0.42 and 27.82 ±â€¯0.9 mmol/L, respectively). The polyherbal mixture lowered the blood glucose level to the normal value (8.64 ±â€¯4.09, 5.26 ±â€¯1.3 and 6.76 ±â€¯1.54 mmol/L in D-10, D-20 and HC groups, respectively). Furthermore, it decreased the levels of total cholesterol, triglycerides, VLDL, LDL, atherogenic and cardiovascular risk indices (p < 0.001) compared to the DC group. In addition, the extract restored histopathological changes of the pancreas, kidneys and liver to the healthy animal level. CONCLUSION: Treatment with the polyherbal mixture extract was more effective than the standard drugs (insulin and metformin) in the amelioration of hyperglycemia, hyperlipidemia, and histopathological changes of the pancreas, kidney and liver tissue.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipolipemiantes/isolamento & purificação , Insulina/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Metformina/farmacologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Plantas Medicinais/química , Ratos , Ratos Wistar
18.
Biomed Pharmacother ; 133: 111085, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378981

RESUMO

Obesity is a significant global health and socio-economic challenge, and considered an important risk factor for poor health outcomes including male reproductive dysfunction and infertility. As excess adiposity causes testicular dysfunction and infertility, novel therapeutic strategies require investigation. Nigella sativa (Ns) seed oil and metformin have both demonstrated a potential positive effect on obesity, although both remain poorly investigated in male fertility. Therefore, this study aimed to determine the effect of Ns oil and metformin on total body weight (TBW), mitochondrial membrane potential (MMP), serum testosterone and semen parameters in an obese animal model. Wistar rats (n = 54) were divided into six groups: normal chow (NC), high sugar diet (HSD) only, HSD and saline, HSD and metformin (75 mg/Kg/day), HSD and Ns (200 mg/Kg/day) (NS200), HSD and Ns (400 mg/Kg/day) (NS400). Intervention was force fed for the last 8 weeks of the 14 weeks dietary exposures. Results showed that the HSD increased TBW (P = 0.001) and reduced sperm concentration (P = 0.013) and progressive motility (P = 0.009) compared to the NC group. Metformin, NS200 and NS400 improved TBW (P = 0.035, P = 0.006 and P = 0.005, respectively) and testosterone (P < 0.001) compared to the HSD saline group, where metformin and NS400 improved sperm concentration (P < 0.001 and P = 0.049, respectively) and MMP (P < 0.001). There were no changes in sperm motility and viability for all experimental exposures, although NS400 (P = 0.047) negatively affected sperm viability. Metformin and Ns may be novel treatment options in obesity-induced infertility, although a potential negative impact on viability is cautioned for high dose Ns. These results warrant further investigation of Ns and Metformin for the management of obese infertile males.


Assuntos
Fármacos Antiobesidade/farmacologia , Fármacos para a Fertilidade Masculina/farmacologia , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/prevenção & controle , Metformina/farmacologia , Obesidade/tratamento farmacológico , Óleos Vegetais/farmacologia , Espermatozoides/efeitos dos fármacos , Testosterona/sangue , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Infertilidade Masculina/sangue , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Obesidade/sangue , Obesidade/patologia , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia
19.
J Ethnopharmacol ; 266: 113444, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33027641

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Acorn obtained from the Quercus liaotungensis Koidz tree is consumed as a Chinese folk medicine for the treatment of diarrhea, abdominal pain, and inflammation, also having strong antioxidant activity and have been utilized for the treatment of diabetes in China. However, its mechanism of action on complications of diabetes and oxidative stress is unclear. AIM OF THE STUDY: The purpose of this research was to assess the effects of acorn (Quercus liaotungensis Koidz) ethanol extract (AE) on pancreatic ß-cell dysfunction through a streptozotocin (STZ)-damaged mouse normal pancreatic ß-cell (MIN6 cell) model in vitro, and by using a high-fat and high-sugar diet with STZ-induced diabetic rat model in vivo to explore the possible mechanism of action against diabetes. MATERIALS AND METHODS: MIN6 cells were pretreated with AE (20, 40, 80 µM) for 2 h and then treated with 3 mM STZ for 24 h. Cell viability was measured by MTT assay. The amount of intracellular reactive oxygen species was measured by 2,7-dichlorodi-hydrofluorescein diacetate. The activities of insulin secretion, superoxide dismutase, catalase and glutathione were determined by kits. Sprague Dawley rats were either given normal feed or a high sugar and fat diet for four weeks, followed STZ (25 mg/kg, via i. p.) was given. Rats with fasting blood glucose ≥11.1 mmol/l after one week were deemed to be diabetic. Animals were divided into 5 groups, which received saline (10 mL/kg), metformin (200 mg/kg), or AE at doses of 200 and 400 mg/kg during 4 weeks by oral gavage. Blood samples were used to evaluate hematological and biochemical indicators, and pancreas was removed for post-analysis. Body weight and fasting blood glucose were recorded weekly. The expression levels of Bax, Bcl-2, p38, p-p38, Nrf2 and HO-1 were determined by Western blot. RESULTS: Data showed that AE inhibited apoptosis and increased antioxidant level in STZ-induced MIN6 cells. In addition, the AE-administered group lowered blood glucose, increased insulin secretion, and alleviated weight loss in the diabetic rats. Histopathologically, the AE-administered group reduced pancreatic injury by significantly restoring the insulin content in ß-islets. It was observed that the anti-diabetic effects of AE were associated with the suppressed the p38 MAPK pathway and actived the Nrf2 pathway. CONCLUSIONS: The ameliorative impact of AE on diabetes may be attributed to protection of the function of pancreatic ß islets and by improving serum insulin levels, hence reducing the blood glucose, which involved in the p38 MAPK and Nrf2 pathways.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Extratos Vegetais/farmacologia , Quercus/química , Animais , Glicemia/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Heme Oxigenase-1/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Insulina/sangue , Masculino , Metformina/farmacologia , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Estreptozocina , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Vnitr Lek ; 66(7): 438-442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380123

RESUMO

Lactic acidosis is a feared complication of metformin therapy. In our article we describe 2 case reports of patients treated with metformin, who developed this complication. In the first case, which was fatal, cummulation of lactate was a result of acute kidney failure caused by diarrhea. In the second patient, lactic acidosis developed in the terrain of preexisting chronic kidney disease, when dyspepsia and decreased fluid intake caused progression into acute kidney failure. In this case, treatment of lactic acidosis was successful. Death of the first patient was probably caused by the presence of serious comorbidities and other complications which developed early after her addmission to intensive care unit. Lactic acidosis can be prevented by strict avoidance of metformin use in case of contraindications and interruption of its use during intercurrent disease.


Assuntos
Acidose Láctica , Diabetes Mellitus Tipo 2 , Metformina , Acidose Láctica/induzido quimicamente , Contraindicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos
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