Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.170
Filtrar
1.
Adv Exp Med Biol ; 1182: 201-215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777020

RESUMO

As extracts from Ganoderma lucidum (G. lucidum, Lingzhi) have been reported to be an alternative adjuvant treatment for diabetes, numerous of work have been carried out on it. Among the many biologically active constituents of Ganoderma, polysaccharides, proteoglycans, proteins, and triterpenoids have been shown to have hypoglycemic effects. Based on our research and other references, this article discusses the antidiabetic effect of Ganoderma mediated by protecting pancreas islet; inhibiting protein tyrosine phosphatase 1B, a promising therapeutic target of diabetes; decreasing lymphocyte infiltration; and increasing the antibody detection of insulin in diabetic mice. This review summarizes researches about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins, and triterpenoids from Ganoderma as a guide for future research on diabetes and its complications. In addition, clinical studies with diabetic indexes are reviewed.


Assuntos
Produtos Biológicos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Reishi/química , Animais , Camundongos
2.
J Photochem Photobiol B ; 201: 111643, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31698218

RESUMO

Diabetes is a major emerging health consequence across the world which directly associated with the obesity. Contemporary anti-diabetic drugs have numeral limitations, and investigation of herbal remedies for diabetes give novel guide for the expansion of new drugs that can be used as harmonizing to present anti-diabetic allopathic medications. Gold nanoparticles (AuNPs) of 21 nm have been formerly well portrayed in vitro for their capability to intend active uptake in cell. Our present study was dealing with the synthesis of gold nanoparticles by means of Smilax glabra rhizome amend the anti-obesity constraints in high-fat diet by streptozotocin provoked obese diabetes in rat model. Characterization studies like UV -Spectroscopy, XRD analysis, SEM, TEM microscopy, Energy Dispersive X-Ray Spectroscopy, and FT-IR investigation confirms the availability of dimension, shape and size. Biochemical parameters like blood glucose and insulin sufferance and its release, lipid profile, aterogenic & coronary index, liver markers, inflammatory markers, hormones like leptin, resistin, adiponectin indicates the therapeutic effect of gold nanoparticles harvested from Smilax glabra on obese and diabetic rats. Histopathological examinations displayed the disturbed internal structures of obese and diabetic rats liver and heart tissues. Whereas, treatment with gold nanoparticles synthesized from Smilax glabra restored the internal membrane, nuclei and cytoplasm. All these findings confirmed the anti-obesity and anti-diabetic effect of synthesized gold nanoparticles from Smilax glabra.


Assuntos
Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Ouro/química , Nanopartículas Metálicas/química , Smilax/química , Animais , Glicemia/análise , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Miocárdio/metabolismo , Miocárdio/patologia , Extratos Vegetais/química , Ratos , Ratos Wistar , Rizoma/química , Rizoma/metabolismo , Smilax/metabolismo , Estreptozocina/toxicidade
3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 355-358, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701722

RESUMO

OBJECTIVE: To investigate the therapeutic effects of puerarin on rats with type 2 diabetes mellitus (T2DM). METHODS: T2DM models were established by high fat and high glucose feeding combined with a one-time intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Then the rats were randomly divided into normal group, model group, metformin group (MET, 40 mg/kg), puerarin low-dose group, medium-dose group and high-dose group (40, 80, 160 mg/kg), n=10. After the model was successfully established, rats were treated with corresponding drug intervention by intragastrical administration for 4 weeks. The body weight and fasting blood glucose (FBG) were measured per week, and blood samples were collected 24 h after the last administration, and serum levels of blood glucose, serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholestrol (HDL-C), serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine (SCr), and blood uric acid (UA) were measured. RESULTS: As compared with normal group, the body weight was decreased after 4 weeks-intervention in the model group, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were all increased,while HDL-C level was decreased (P<0.05). As compared with model group,the body weight was increased after 4 weeks-intervention in metformin group and puerarin groups, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were decreased (P<0.01); meanwhile, HDL-C level was increased significantly (P<0.05). CONCLUSION: Puerarin can reduce the weight loss of T2DM rats, decrease the blood lipid and blood glucose levels of T2DM rats, which can be used to control T2DM.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Isoflavonas/farmacologia , Animais , Glicemia , Lipídeos/sangue , Distribuição Aleatória , Ratos , Estreptozocina , Perda de Peso
4.
Int J Nanomedicine ; 14: 7743-7758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571874

RESUMO

Purpose: Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized. Materials and methods: A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles. Results: They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy. Conclusion: CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.


Assuntos
Alginatos/química , Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Vitamina B 12/química , Administração Oral , Alginatos/síntese química , Animais , Células CACO-2 , Morte Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina B 12/síntese química
5.
J Agric Food Chem ; 67(45): 12472-12480, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31642672

RESUMO

Brown macroalgae are an important source of polyphenols with multiple health functions. In this work, polyphenol extracts from Lessonia trabeculate were purified and investigated for the antidiabetic activity in vitro and in vivo. The purified polyphenol extracts exhibited good antioxidant activities, α-glucosidase and lipase inhibition activities (IC50 < 0.25 mg/mL). The HPLC-DAD-ESI-MS/MS analysis indicated that the compounds in polyphenol extracts were mainly phlorotannin derivatives, phenolic acid derivatives, and gallocatechin derivatives. In vivo, C57BL/6J rats treated with polyphenol extracts for 4 weeks had lower fasting blood glucose levels, insulin levels, as well as better serum lipid profiles and antioxidant stress parameters, compared with the diabetic control (DC) group. Histopathology revealed that polyphenol extracts preserved the architecture and function of the liver. Short-chain fatty acid contents in rats' fecal samples with polyphenols administration were significantly recovered as compared with the DC group. Furthermore, the gut microflora of rats was investigated with high-throughput 16S rRNA gene sequencing and results indicated that polyphenol extracts had a positive effect on regulating the dysbiosis of the microbial ecology in diabetic rats. All of the results from the study provided a scientific reference of the potentially beneficial effects of L. trabeculate polyphenols on diabetes management.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Feófitas/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Alga Marinha/química , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Ratos , Estreptozocina/efeitos adversos
6.
Chem Biol Interact ; 312: 108819, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499052

RESUMO

Cannabidiol (CBD), a compound obtained from Cannabis sativa, has wide range of therapeutic properties, including mitigation of diabetes and neurodegeneration. Cerebral ischemia and consequent learning disabilities are aggravated in elderly diabetic subjects. However, there are no studies showing the effect of CBD treatment in elderly diabetes patients suffering cerebral ischemia. The present work tested the hypothesis that CBD treatment improves metabolic dysfunctions in middle-aged diabetic rats submitted to chronic cerebral hypoperfusion. In this work, 350-day-old male Wistar streptozotocin-induced diabetic rats were used. To induce cerebral ischemia was used a chronic cerebral hypoperfusion (CCH), surgically, via the four-vessel occlusion/internal carotid artery (4-VO/ICA). Four diabetic groups were established: Non-CCH Treated Diabetic (DNT), CCH Treated Diabetic (DCT), Non-CCH Vehicle Diabetic (DNV), and CCH Vehicle Diabetic (DCV). Vehicle groups were not treated with CBD. The animals were treated during 30 days with 10 mg CBD/Kg bw/day. After treatment, the animals were euthanized, and blood levels of glucose, insulin, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fructosamine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. DCT group presented reduction of hyperglycemia and an increase of insulinemia. Also was observed lower fructosamine, LDL, HDL, triglycerides and total cholesterol levels. AST and ALT concentration were reduced in CBD treated groups. CBD may be used as therapeutic tool to protect metabolism against injuries from diabetes aggravated by cerebral ischemia.


Assuntos
Isquemia Encefálica/patologia , Canabidiol/uso terapêutico , Diabetes Mellitus Experimental/patologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/análise , Isquemia Encefálica/complicações , Colesterol/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Insulina/sangue , Masculino , Ratos , Ratos Wistar
7.
J Biol Regul Homeost Agents ; 33(5): 1327-1335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487982

RESUMO

The glucose transporter 4 (GLUT4) translocation is a vital link of insulin-induced glucose uptake in adipose tissue and skeletal muscle. It is an important topic in anti-diabetic research to explore novel agents to facilitate the role of insulin. The aim of this study was to verify the hypothesis that neuropeptide galanin may enhance insulin-induced GLUT4 translocation to increase glucose uptake in adipose tissue of type 2 diabetic models. Insulin and/or galanin were injected respectively or cooperatively into type 2 diabetic rats once a day for fifteen days. The results showed that administration of galanin significantly enhanced insulin-induced GLUT4 and vesicle-associated membrane protein 2 (VAMP2) translocation, Akt phosphorylation and glucose uptake, but not GLUT4 mRNA and protein expression levels in adipose cells. The beneficial roles of galanin on insulin-induced events may be blocked by MK-2206, an Akt inhibitor, indicating that the Akt phosphorylation is essential for promoting impact of galanin on the insulin-induced events. These results suggest that galanin may benefit insulin-induced GLUT4 and VAMP2 translocation, and subsequent glucose uptake via the activated Akt-VAMP2-GLUT4 pathway in adipose cells. These findings deepen our understanding of the anti-diabetic effect of galanin and its mechanism.


Assuntos
Adipócitos/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Galanina/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Insulina/farmacologia , Animais , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteína 2 Associada à Membrana da Vesícula/metabolismo
8.
Int J Nanomedicine ; 14: 4895-4909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456636

RESUMO

Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, -16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, -16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.


Assuntos
Liofilização , Insulina/administração & dosagem , Polieletrólitos/química , Polietilenoglicóis/administração & dosagem , Polietilenoimina/administração & dosagem , Administração Oral , Animais , Crioprotetores/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Ponto Isoelétrico , Masculino , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Fatores de Tempo
9.
Adv Exp Med Biol ; 1155: 87-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468388

RESUMO

The present study has investigated the effect of adding taurine (TAU) to a treatment of diabetes with metformin (MET), a hypoglycemic, and lovastatin (LOV), an antihyperlipidemic. To this end, male Sprague-Dawley rats, agent, 250-275 g in weight, were made diabetic with a single 60 mg/kg intraperitoneal (i.p.) dose of streptozocin (STZ) in 10 mM citrate buffer pH 4.5, and, after 14 days, treated daily with oral doses of MET (2.4 mM/kg), LOV (0.075 mM/kg) or TAU (2.4 mM/kg), and with binary and ternary combinations of these agents. Rats receiving only 10 mM citrate buffer pH 4.5 or only STZ served as negative and positive controls, respectively. In addition, rats receiving insulin (INS, 4 units/kg) by the subcutaneous route served as a reference treatment. All the rats were sacrificed on day 57 and their bloods collected into heparinized tubes. The corresponding plasma samples were analyzed for their glucose (GLC), insulin (INS), glycated hemoglobin (HbA1c), cholesterol (CHOL) and triglycerides (TG) contents. In comparison to normal rats, diabetic ones showed marked increases in GLC (+313%), HbA1c (+207%), CHOL (+66%) and TG (+188) and a profound decrease of INS levels (-76%) (p < 0.001 vs. control values). Among the various treatments, one with INS produced the greatest lowering effect on the plasm a GLC (+23%, p < 0.05), INS (+23%, p < 0.05) and TG (+3%), with the remaining changes being similar to those seen with MET. A treatment with MET reduced all the diabetic changes by at least threefold; and one with LOV had a significant (p < 0.001) lowering effect on the plasma CHOL and TG but was without an effect on the plasma GLC, INS and HbA1c. In common with LOV, TAU reduced the diabetic levels of both CHOL and TG and, in addition, reduced the diabetic plasma GLC and raised the corresponding INS level. Among binary combinations, one with LOV-MET provided a greater effect than MET alone only in terms of the plasma CHOL and TG; and one with LOV-TAU was only significantly better than TAU alone in lowering the TG levels. However, a treatment with LOV-MET-TAU led to reductions in all the plasma parameters examined that were much greater than those achieved with any of the individual agents or with their binary combinations (at p ≤ 0.05).


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lovastatina/farmacologia , Metformina/farmacologia , Taurina/farmacologia , Animais , Glicemia , Carboidratos/sangue , Hipolipemiantes/farmacologia , Insulina , Lipídeos/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina
10.
Adv Exp Med Biol ; 1155: 369-380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468415

RESUMO

The present study was carried out in diabetic rats to examine the effects of ethanol (EtOH) and taurine (TAU), singly and in combination, in reducing the changes of laboratory test values indicating renal dysfunction. For this purpose, male Sprague-Dawley rats, 250-280 g in weight and in groups of 6, were made diabetic with a single, 60 mg/kg intraperitoneal dose of streptozotocin in 10 mM citrate buffer pH 4.5. On day 15 and for the remaining 14 days of the study, the diabetic rats (a) started to drink 5% EtOH in place of water, (b) received a single daily 2.4 mM/kg oral dose of TAU or (c) were allowed to drink 5% EtOH after receiving a dose of TAU. Starting from day 28 and ending on day 29, a 24 h urine sample was collected, its volume was measured, and then used to measure glucose (GLC), total protein (TP) and electrolytes (Na+, K+, Ca++, Mg++). Blood samples collected immediately thereafter via cardiac puncture were processed for the plasma fractions which were analyzed for their creatinine (CRT) and urea nitrogen (UN) contents. In comparison to normal (control) rats, diabetic ones showed a higher output of urine (+5.6-fold), a massive increase in plasma GLC (+473%), passed more GLC (+73.8-fold) and TP (+8.2-fold) in the urine, showed higher plasma CRT (+241%) and UN (+74%) levels, a lower plasma UN/CRT ratio (-47%) and a greater output of electrolytes in the urine (by at least twofold). By themselves both EtOH and TAU were found to markedly lower the effects of diabetes, with EtOH generally appearing more effective than TAU. However, the concurrent availability of EtOH and TAU was found to be more protective than either treatment alone.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/farmacologia , Nefropatias/tratamento farmacológico , Taurina/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental/complicações , Nefropatias/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Urinálise
11.
Life Sci ; 233: 116728, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31386877

RESUMO

Impaired wound healing is a serious concern of uncontrolled hyperglycemia that can lead to gangrene, and even death. There is an urgent need to look for better alternative therapy because of the undesirable side effects of currently available synthetic drugs in the market. Syringic acid (SA) is a natural phenolic compound abundantly available in edible fruits and plants. In this study, wound healing activities of 2.5% and 5.0% SA were evaluated in type 2 diabetic rats using incisional wound model. SA-treated diabetic wounds showed faster rate of wound closure and epithelization with enhanced contents of hydroxyproline and protein compared to diabetic wounds. SA effectively prevents alterations in blood glucose levels, serum insulin and dyslipidemia in diabetic wound rats. The SA-treated diabetic wounds after 14 days of treatment demonstrated inhibition of pro-inflammatory response (NF-κB p65, TNF-α, IL-1ß, IL-8 and IL-2) with improvement in anti-inflammatory response (IL-10), inhibited the elevated oxidative stress and decreased the concentrations of matrix metalloproteinases (MMP-2, -8 and -9) and increased the concentrations of TIMP-1 & TIMP- 2. Furthermore, the diabetic wounds were presented with an increase in expression of CD 31 and 68, growth factors (TGF-ß1, collagen-I and α-SMA and VEGF) with significant improvement in collagen deposition, re-epithelialization and complete skin structure as revealed by histological analysis after treatment of diabetic wounds with SA for 14 days. Hence, the results of this study designate that SA significantly improves wound healing in diabetic rats and could be used as a potential therapy for treatment of diabetic wounds.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ácido Gálico/análogos & derivados , Regulação da Expressão Gênica/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Ácido Gálico/farmacologia , Insulina/sangue , Lipídeos/análise , Masculino , Ratos , Ratos Wistar
12.
Pestic Biochem Physiol ; 159: 127-135, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400774

RESUMO

Pesticides cardiotoxicity in case of diabetic-induced cardiac complications is unidentified. The probable amelioration role of propolis is gauged against the cardiotoxic effects of chlorpyrifos in the diabetic rats through paraoxonase-1 (PON1) and xanthine oxidase (XO) genes dysregulation. Fifty-six male rats were distributed (n = 7) into eight groups. The first one saved as control whereas the 2nd, 3rd, and 4th were kept for propolis aqueous extract (100 mg/kg), diabetes (60 mg/kg streptozotocin) and chlorpyrifos (2.5 mg/kg), respectively. The 5th was diabetes/chlorpyrifos combination, while 6th, 7th, and 8th were intubated with propolis for four weeks after diabetic induction, chlorpyrifos intoxication, and their combination, respectively. The plasma glucose, lipid profiles, cardiac enzymes and interleukin-6 (IL-6) significantly elevated, while insulin decreased in the diabetic and combination groups. Although the cardiac acetylcholinesterase, total thiols, and PON1 significantly reduced after diabetic and/or chlorpyrifos gavage, the protein carbonyl, superoxide dismutase, catalase, and XO significantly elevated. The mRNA genes expression of PON1 and XO have also confirmed the enzymatic activities. Interestingly, propolis significantly restored the hyperglycemia, hypoinsulinemia, hyperlipidemia, IL-6 elevations, and antioxidant defense system disorder. These records revealed that the immunomodulatory, anti-diabetic and antioxidant tasks are fine pointers for the cardiovascular defender of propolis especially during diabetes and/or pesticides exposure.


Assuntos
Arildialquilfosfatase/metabolismo , Clorpirifos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Própole/uso terapêutico , Xantina Oxidase/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Inseticidas/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos
13.
Orv Hetil ; 160(32): 1270-1278, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31387373

RESUMO

Introduction: During recent decades, the perinatal mortality of extremely low-birth weight infants has decreased. An important task is to recognize complications of prematurity. Aim: We made an attempt to explore the relationship between complications of prematurity and neonatal hyperglycemia. Method: From 1 January 2014 to 31 December 2017, 188 infants with birth weight below 1000 g were admitted. For each infant, the frequencies of hyperglycemia (blood glucose >8.5 mmol/l), retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were determined. Animal studies were performed in Sprague Dawley rats. Hyperglycemia was achieved by intraperitoneal injection of streptozotocin (100 mg/kg). On the 7th day of life, aorta sections were prepared and stained with hematoxylin eosin. Wall thickness was measured using QCapture Pro 7 image analysis software. Results: The mean ± SD gestational age and birth weight were 27.1 ± 2.2 weeks and 814.9 ± 151.9 g; 33 infants (17.5%) died. Hyperglycemia was confirmed in 62 cases (32.9%), and insulin treatment was given to 43 infants (22.8%). The gestational age and birth weight of the hyperglycemic infants were significantly lower (p<0.001), the incidence of severe retinopathy (p = 0.012) and the mortality of insulin-treated patients were higher (p = 0.02) than in normoglycemic infants. Among survivors (n = 155), we found by logistic regression analysis that hyperglycemia was a risk factor for severe retinopathy (p<0.001). In the rat model, neonatal hyperglycemia caused significant thickening of the aortic wall. Conclusion: Our studies indicate that hyperglycemia is common in extremely low birth-weight infants. Monitoring of these infants for retinopathy of prematurity, kidney dysfunction, and hypertension is recommended. Orv Hetil. 2019; 160(32): 1270-1278.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Doenças do Prematuro , Retinopatia da Prematuridade/etiologia , Animais , Peso ao Nascer , Displasia Broncopulmonar/epidemiologia , Hemorragia Cerebral Intraventricular/epidemiologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Gravidez , Ratos , Ratos Sprague-Dawley , Retinopatia da Prematuridade/epidemiologia
14.
Life Sci ; 234: 116755, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415769

RESUMO

AIMS: Vitamin D and its receptor, vitamin D receptor (VDR), have renoprotection effect against diabetic nephropathy (DN). But the exact mechanism has not been fully elucidated. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP) epoxygenase-derived metabolites of arachidonic acid, protecting against diabetes and DN. Herein, we hypothesized that activation of VDR attenuated high glucose-induced cellular injury in renal tubular epithelial cells partially through up-regulating CYP2J5 expression. MAIN METHODS: Streptozotocin (STZ) was injected to induce diabetic in wild type and Vdr-/- mice. The effects of VDR knockout and an activator of VDR, paricalcitol, on the renal injury were detected. In vitro, a murine kidney proximal tubule epithelial cell line BU.MPT induced by high glucose were treated with or without paricalcitol (30 mM) for 12 h or 24 h. KEY FINDINGS: The expression of CYP2J5 was significantly decreased both in wild type and Vdr-/- diabetic mice induced by STZ. The STZ-induced kidney architecture damage and apoptosis rate in Vdr-/- mice were more severe. In vitro, high glucose treatment strongly reduced the CYP2J5 expression and the synthesis of 14,15-EET in BU.MPT cells. Supplement of 14,15-EET significantly reduced the lactate dehydrogenase (LDH) release induced by high glucose in BU.MPT cells. Furthermore, treatment with paricalcitol attenuated cellular injury and restored the expression of CYP2J5 reduced by high glucose in BU.MPT cells. SIGNIFICANCE: We conclude that activation of VDR attenuates high glucose-induced cellular injury partially dependent on CYP2J5 in murine renal tubule epithelial cells and paricalcitol may represent a potential therapy for DN.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Ergocalciferóis/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Receptores de Calcitriol/agonistas , Animais , Linhagem Celular , Sistema Enzimático do Citocromo P-450/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Ergocalciferóis/uso terapêutico , Deleção de Genes , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Knockout , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo
15.
Biomed Khim ; 65(4): 311-315, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31436172

RESUMO

It was studed basal and ACTH-stimulated production of cyclic adenosine monophosphate (cAMP) and corticosteroid hormones (progesterone and corticosterone) in rat adrenals in vitro under streptozotocin diabetes, in conditions of mifepristone administration and their combination. It was shown that in streptozotocin diabetes animals, both the basal and adrenocorticotropic hormone (ACTH) stimulated cAMP production significantly increased; this was accompanied by the increase in basal and ACTH-stimulated progesterone and corticosterone production in rat adrenals in vitro. Repeated administration of mifepristone to control and diabetic rats caused an increase mainly in ACTH-stimulated production of the main glucocorticoid hormone, corticosterone, without additional changes in the cAMP level. The results obtained suggest activation of two mechanisms of steroidogenesis enhancement in experimental animals. In rats with streptozotocin diabetes, both basal and ACTH-stimulated activity of all stages of steroidogenesis increase, which is mediated by the increased formation of cAMP as second messenger mediating the ACTH action on adrenocortical cells. Prolonged administration of mifepristone to control and diabetic rats resulted in increased activity of only late stages of steroidogenesis with predominant elevation of synthesis of physiologically active hormone corticosterone without additional changes in cAMP production level.


Assuntos
Hiperfunção Adrenocortical/fisiopatologia , AMP Cíclico/fisiologia , Diabetes Mellitus Experimental/tratamento farmacológico , Mifepristona/farmacologia , Hiperfunção Adrenocortical/complicações , Hormônio Adrenocorticotrópico/fisiologia , Animais , Corticosterona/fisiologia , Diabetes Mellitus Experimental/complicações , Ratos
16.
DNA Cell Biol ; 38(10): 1134-1142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433203

RESUMO

Diabetes mellitus is a complicated metabolic disease characterized by hyperglycemia. Diabetic nephropathy (DN) is a progressive kidney disease, which results in mortality in diabetic patients. The present study was designed to investigate the effect of applying spironolactone (S), captopril (C), and their combination (S+C) on some renal performance indices and microRNAs' (miRNAs) expression. A total of 35 two-month-old male Wistar rats were provided for the study. Intraperitoneal injection of freshly dissolved streptozotocin (60 mg/kg) in cold citrate buffer was used to induce diabetes. Blood samples were examined through calorimetry to assess serum concentrations of glucose, blood urea nitrogen (BUN), and creatinine. To measure the microalbuminuria and transforming growth factor-ß (TGF-ß) levels and to evaluate the miRNAs expression levels of the kidney tissue, the ELISA method and the real-time PCR were used. The obtained results serve as in vivo evidence for the positive relationship between miR-192 and TGF-ß levels in the DN rats. A significant increase and decrease were found for miR-29a/b/c and the miR-192 expression of DN after treatment with S, C, and S+C. TGF-ß levels and microalbuminuria of diabetic rats also increased. The results obtained from this research study suggest that S, C, and S + C can improve DN by targeting miR-192 and miR-29 family and changing their expression. These findings suggest that miR-192 and miRs-29a/b/c can be potential targets for DN remediation.


Assuntos
Captopril/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Espironolactona/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Diuréticos/farmacologia , Combinação de Medicamentos , Reposicionamento de Medicamentos , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Hiperglicemia/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Ratos Wistar , Estreptozocina/administração & dosagem , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento
17.
Georgian Med News ; (290): 144-149, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322533

RESUMO

There have been presented the results of the histomorphological research of the effect of the beans' thick extract (BTE) on the state of the pancreas on the model of diabetes mellitus type 2 on the background of obesity in the rats in our research. The simulation of type 2 diabetes on the background of obesity in the animals has led to the development of signs of insulin's inhibition of insulin producing apparatus - some different expressions of dystrophy and degeneration of the ß-cells. The consequence of the hyperfunction has been exhaustion and even death of ß-cells, the development of the diabetic condition. The redistribution of pancreatic islet ß-content of cells has contributed to the increase of the small islands and had a compensatory nature. The treatment of the animals by the BTE has fully prevented an excessive negative impact on revenues of carbohydrates insulin producing apparatus, because it improves the morphological status of ß-cells, reduces the part of small pancreatic islets, almost restores medium and large islets to the level of the «Intact control¼ group. The comparison drug - metformin - has a positive effect on the morphological status of the pancreatic ß-cells, but this effect is obviously not enough for improving or restoring the normal % of distribution of islets.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes/uso terapêutico , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Obesidade/complicações , Extratos Vegetais/uso terapêutico , Sementes/química , Animais , Tamanho Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Metformina/administração & dosagem , Extratos Vegetais/química , Ratos , Açúcares
18.
Chem Commun (Camb) ; 55(61): 8975-8978, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290492
19.
Int J Nanomedicine ; 14: 4383-4395, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354267

RESUMO

Background: The bioactive compounds glycyrrhizin (GL) and thymoquinone (TQ) have been reported for antidiabetic activity in pure and nanoformulation (NF) form. However, the antidiabetic effect of a combined nanoformulation of these two has not been reported in the literature. Here, a combinational nanomedicine approach was investigated to enhance the antidiabetic effects of the two bioactive compounds of GL and TQ (GT), in type 2 diabetic rats in reference to metformin. Methods: Two separately prepared NFs of GL (using polymeric nanoparticles) and TQ (using polymeric nanocapsules) were mixed to obtain a therapeutic cargo of nanomedicine and then characterized with respect to particle size, stability, morphology, chemical interaction, and in vivo behavior. Additionally, NFs were evaluated for their cytotoxic effect on Vero cell lines compared to the pure form. This nanomedicine was administered orally, both independently and in combination (pure form or NF) for 21 successive days to type 2 diabetic rats and the effect assessed in term of body weight, fasting blood-glucose level, and various biochemical parameters (such as lipid-profile parameters and HbA1c). Results: When these nanomedicines were applied in combined rather than individual forms, significant decreases in blood glucose and HbA1c and significant improvements in body weight and lipid profile were observed, despite them containing lower amounts than the pure forms. The treatment of diabetic rats with GL and TQ, when administered independently in either pure or NF forms, did not lead to favorable trends in any studied parameters. Conclusion: The administration of combined GT NFs exhibited significant improvement in studied parameters. Improvements in antidiabetic activity could have been due to a synergistic effect of combined NFs, leading to enhanced absorption of NFs and lesser cytotoxic effects compared to pure bioactive compounds. Therefore, GT NFs demonstrated potential as a new medicinal agent for the management of diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Composição de Medicamentos , Hipoglicemiantes/uso terapêutico , Nanopartículas/química , Polímeros/química , Animais , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Feminino , Hemoglobina A Glicada/metabolismo , Ácido Glicirrízico/uso terapêutico , Hipoglicemiantes/administração & dosagem , Lipídeos/química , Nanopartículas/ultraestrutura , Niacinamida , Polímeros/efeitos adversos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Estreptozocina
20.
Life Sci ; 233: 116698, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356906

RESUMO

AIM: Type 1 diabetes (T1DM) is a common chronic disease in childhood. Increasing insulin resistance in puberty gives rise to higher doses of insulin usage in treatment. Of this reason new approaches in treatment are needed. Noopept researches suggest it to have anti-diabetic properties. We tried to determine the effects of noopept on pubertal diabetes. MAIN METHOD: The research was made with 60 prepubertal, 28 day-old, male, Sprague Dawley rats. The rats were divided into randomised 6 groups (n = 10/group). i) Control, ii) Diabetes Control, iii) Noopept Control, iv) Diabetes + Noopept, v) Diabetes + Insulin, vi) Diabetes + Insulin + Noopept. T1DM model was induced by streptozotocin on postnatal 28th day. 0.5 mg/kg noopept and 1 IU insulin were administered intraperitoneally for 14 days. Blood glucose and body weight measurements, puberty follow-up and MWM tests were performed. Hippocampus, hypothalamus and testis were evaluated histologically. Hypothalamic GnRH and kisspeptin were studied immunohistochemically. Serum LH, FSH and insulin, hippocampal homogenate NGF and BDNF levels were determined by ELISA. KEY FINDINGS: Delayed puberty was normalized by noopept (p < 0.05). Blood glucose levels were lower in noopept-administered diabetic groups (p < 0.05). Noopept decreased HOMA-IR in insulin administered diabetic group (p < 0.05). Number of degenerated cells in hippocampus and testis were higher in diabetes control group when compared with other groups (p < 0.05). GnRH immunoreactivity in Diabetes + Noopept group was increased when compared to insulin + noopept group (p = 0.018). There was no difference in kisspeptin, serum LH, FSH, hippocampal NGF-BDNF levels and spatial learning assessment among groups (p > 0.05). SIGNIFICANCE: Noopept may have positive effect in treatment of pubertal diabetes.


Assuntos
Cognição/fisiologia , Diabetes Mellitus Experimental/tratamento farmacológico , Dipeptídeos/farmacologia , Resistência à Insulina , Fármacos Neuroprotetores/farmacologia , Puberdade/fisiologia , Animais , Glicemia/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Insulina/metabolismo , Masculino , Fator de Crescimento Neural/metabolismo , Puberdade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA