Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.314
Filtrar
1.
Postepy Biochem ; 65(3): 224-230, 2019 10 01.
Artigo em Polonês | MEDLINE | ID: mdl-31643170

RESUMO

Berberine (BRB) is a compound belonging to the group of isoquinoline alkaloids of plant origin that has long been used in traditional chinese medicine (TMC). Due to, among others anti-inflammatory properties BRB is a potential therapeutic in the treatment of acute pancreatitis (OZT). In a study in the mouse model of L-arginine-induced acute pancreatitis, we showed that BRB administered by the intravenous route at 0.1 and 0.5 mg / kg body weight significantly reduces the level of myeloperoxidase activity (an indicator of inflammation) in the pancreas and lungs. Promising results point to the need for larger, randomized studies to assess the long-term efficacy and side effects of BRB therapy.


Assuntos
Berberina/uso terapêutico , Pancreatite/tratamento farmacológico , Doença Aguda/terapia , Animais , Berberina/farmacologia , Modelos Animais de Doenças , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia
2.
Anticancer Res ; 39(10): 5339-5344, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570427

RESUMO

BACKGROUND/AIM: Gemcitabine is standard first-line treatment for patients with advanced pancreatic cancer, however the efficacy is limited. Although acquired drug resistance and side-effects are known to limit efficacy, opposite effects of a drug, which enhance the malignancy of treated cancer, have been observed but are not well understood. The aim of the present study was to determine whether gemcitabine has such opposite effects on the BxPC-3 human pancreatic cancer cell line expressing green fluorescent protein (BxPC-3-GFP) in an orthotopic mouse model. MATERIALS AND METHODS: BxPC-3-GFP tumors grown subcutaneously in nude mice were harvested. Tumor fragments were orthotopically implanted in the tail of the pancreas of nude mice using the technique of surgical orthotopic implantation. The BxPC-3-GFP orthotopic models were divided randomly into three groups: Group 1: untreated control; Group 2: low-dose gemcitabine (weekly intraperitoneal injection at 25 mg/kg for 6 weeks); Group 3: high-dose gemcitabine (weekly intraperitoneal injection at 125 mg/kg for 6 weeks). Each group comprised eight mice. Tumor size, fluorescent area of metastases, and body weight were measured. RESULTS: Low- and high-dose gemcitabine inhibited primary tumor growth in a dose-dependent manner, and to the greatest extent by high-dose gemcitabine compared to the untreated control (p=0.0134). In contrast, the extent of metastasis on the peritoneum was significantly increased by low-dose gemcitabine compared to the untreated control (p=0.0112). The extent of metastasis showed no significant difference between the untreated control and mice treated with high-dose gemcitabine. Body weight of the treated mice was not significantly different from that of the untreated mice. CONCLUSION: The use of very bright GFP expressing of BxPC-3 cells and the orthotopic model demonstrated an unexpected increase in metastasis by low-dose gemcitabine. Future experiments will investigate the mechanism of this phenomenon.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Metástase Neoplásica/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Camundongos Nus , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo
3.
Anticancer Res ; 39(10): 5369-5374, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570431

RESUMO

BACKGROUND/AIM: Cytokine-induced killer (CIK) cells are ex vivo expanded major histocompatibility complex (MHC)-unrestricted cytotoxic cells with promising effects against a variety of cancer types. Regulatory T-cells (T-reg) have been shown to reduce the effectiveness of CIK cells against tumor cells. Peptide P60 has been shown to inhibit the immunosuppressive functions of T-regs. This study aimed at examining the effect of p60 on CIK cells efficacy against renal and pancreatic cancer cells. MATERIALS AND METHODS: The effect of P60 on CIK cytotoxicity was examined using flow cytometry, WST-8-based cell viability assay and interferon γ (IFNγ) ELISA. RESULTS: P60 treatment resulted in a significant decrease in the viability of renal and pancreatic cancer cell lines co-cultured with CIK cells. No increase in IFNγ secretion from CIK cells was detected following treatment with P60. P60 caused no changes in the distribution of major effector cell populations in CIK cell cultures. CONCLUSION: P60 may potentiate CIK cell cytotoxicity against tumor cells.


Assuntos
Células Matadoras Induzidas por Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Fatores de Transcrição Forkhead/antagonistas & inibidores , Neoplasias Renais/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura/métodos , Células Matadoras Induzidas por Citocinas/metabolismo , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Interferon gama/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Neoplasias Renais/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
4.
Anticancer Res ; 39(10): 5821-5830, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570487

RESUMO

BACKGROUND/AIM: The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC). PATIENTS AND METHODS: A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed. RESULTS: The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005). CONCLUSION: The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival.


Assuntos
Jejuno/patologia , Neoplasias Pancreáticas/patologia , Veia Porta/patologia , Idoso , Quimiorradioterapia/métodos , Feminino , Humanos , Jejuno/efeitos dos fármacos , Jejuno/efeitos da radiação , Masculino , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/efeitos da radiação , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Veia Porta/efeitos dos fármacos , Veia Porta/efeitos da radiação , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 140-144, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250605

RESUMO

OBJECTIVE: To investigate the therapeutic effects of the black buckwheat leaf (BBL) in type 2 diabetes mellitus mice and its effects on pancreas and spleen. METHODS: Forty male C57 / B16 mice (SPF) were randomly divided into normal control (NC) group (n=10) and the experimental group (n=30), the experimental group were fed with high sugar and high fat, combined with intraperitoneal injection of streptozotocin in small dose to establish the model of type 2 diabetes mellitus (T2DM). Those thirty model mice were randomly divided into 3 groups (n=10), diabetes mellitus group (DM), low dose of BBL (DM+L) treated group, high dose of BBL (DM+H) treated group. The mice in the NC group and the DM group were given normal saline per day, and the DM+L group and DM+H group were treated with black tartary buckwheat at the doses of 0.21g/kg·d-1 and 0.42g/kg·d-1 respectively. After 14 days. All mice were executed by cervical dislocation, then blood samples were collected, pancreas and spleen were removed for subsequent experiments. The serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TCH) and insulin were detected. TNF-α protein in spleen tissue was detected by ELISA kit. The morphology of pancreas tissue was observed by HE staining, and the spleen coefficient was calculated. The expression levels of insulin receptor substrate-1(IRS-1) mRNA and IRS-1 protein in pancreatic tissue were detected. RESULTS: Compared with the control group, the serum levels of FBG, TC and TCH in the model group were increased significantly, while the serum level of insulin was decreased significantly (P<0.05), the expression of TNF-α protein in spleen tissues was obviously raised, the expressions of IRS-1 mRNA and IRS-1 protein in pancreatic tissue in model group were decreased significantly (P<0.05). Compared with the model group, the serum levels of FBG, TC and TCH were decreased significantly in the BBL treated groups. The serum insulin level, spleen coefficient, TNF-α protein expression level in spleen tissue, IRS-1 mRNA expression and IRS-1 protein expression levels in pancreatic tissue in BBL treated group were increased significantly (P< 0.05). High-dose black tartary buckwheat leaves (0.42g/kg·d-1) exerted a more significant effect. CONCLUSION: Stem and leaf of black bitter buckwheat has significant therapeutic effects on reducing blood sugar and blood fat in type 2 diabetic mice, and has certain protective effects on pancreas and spleen of diabetic mice.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Fagopyrum/química , Pâncreas/efeitos dos fármacos , Baço/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Folhas de Planta/química , Caules de Planta/química , Distribuição Aleatória , Estreptozocina
6.
World J Emerg Surg ; 14: 18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31007709

RESUMO

Background: Severe acute pancreatitis is associated with high morbidity and mortality. Melatonin is known as the activator of antioxidant enzymes. The main purpose of this study was to evaluate the clinical effect of melatonin treatment in a pig model with induced acute pancreatitis. Methods: In this study, acute pancreatitis was induced in 38 German domestic pigs (German Hybrid). After induction of acute pancreatitis, 18 animals were treated with melatonin. Intraoperative clinical data, postoperative blood parameters, fitness, and Porcine Well-being (PWB) score, and post-mortal histopathological data were analyzed in both study groups. Results: The matching procedure created two groups (melatonin group and control group) which were very similar. The fitness and PWB score were postoperative significantly enhanced in the melatonin group as compared to the control group (p = 0.005 and p = 0.003). Additionally, histological analysis revealed that acinar necrosis, fat tissue necrosis, and edema were significantly reduced in the melatonin group as compared to the non-melatonin group (p = 0.025, p = 0.003, and p = 0.028). Conclusions: Pigs, which were treated with melatonin, were characterized by higher fitness and PWB scores than those of the control group. Moreover, melatonin treatment reduces the acinar necrosis, fat tissue necrosis, and edema of pancreatic tissue. Thus, melatonin might be a useful therapeutic option in severe acute pancreatitis.


Assuntos
Melatonina/farmacologia , Pancreatite/tratamento farmacológico , Animais , Modelos Animais de Doenças , Alemanha , Melatonina/uso terapêutico , Pâncreas/efeitos dos fármacos , Pâncreas/lesões , Aptidão Física/fisiologia , Análise de Sobrevida , Suínos , Resultado do Tratamento
7.
Food Chem Toxicol ; 128: 280-285, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004718

RESUMO

Carvacrol (5-isopropyl-2-methylphenol) is a biologically active monoterpene phenol abundantly present in the essential oils of many Lamiaceae aromatic/ethnomedicinal plants. Herein, we aimed to evaluate the damaging effect of carvacrol to rat pancreatic tissue, but also to assess its possible ameliorative impact on pancreatic damage induced by L-arginine. The toxic and beneficial (in a dose of 10 mg/kg) properties of carvacrol were assessed by measuring serum α-amylase and lipase activities, tissue malondialdehyde (MDA) content, and pathohistological changes in pancreatic tissue. Application of 100/500 mg/kg of carvacrol produced a significant increase in α-amylase activity, followed by inflammatory-cell infiltration and patchy interlobular edema in the pancreas. In the L-arginine-induced pancreatitis model, a dose of 10 mg/kg of carvacrol prevented an increase in α-amylase and lipase activities, and MDA formation, when compared to the animals that received L-arginine only. Animals treated with carvacrol prior to L-arginine administration displayed mild edema and inflammatory infiltration with few necrotic areas. Contrary to that, animals that received only L-arginine showed a massive leukocyte infiltrate with edema and substantial necrotic areas. In our study carvacrol showed significant protective effects and a potential to modulate leukocyte recruitment in pancreatic tissue after L-arginine injection.


Assuntos
Arginina/toxicidade , Monoterpenos/farmacologia , Monoterpenos/toxicidade , Pâncreas/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Lipase/sangue , Masculino , Malondialdeído/metabolismo , Monoterpenos/administração & dosagem , Tamanho do Órgão/efeitos dos fármacos , Pancreatite/enzimologia , Pancreatite/metabolismo , Pancreatite/patologia , Ratos , Ratos Wistar , alfa-Amilases/sangue
8.
Pancreas ; 48(4): 488-495, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30946233

RESUMO

OBJECTIVES: This study aimed to compare the clinical course of 5-aminosalicylic acid-derived, drug-induced acute pancreatitis (5-ASA-DIAP) to acute pancreatitis (AP) caused by other etiologies. METHODS: A cohort of patients with 5-ASA-DIAP was established through literature search. As a control AP (CAP) group, a cohort was generated from a registry. Data on the diagnostic procedure, symptoms, enzyme elevation, imaging, severity, and recovery parameters were collected. Causality was assessed using the Naranjo algorithm. RESULTS: Twenty-nine articles were included, which describe 36 patients with fifty-one 5-ASA-DIAP episodes (60.78% female, 39.22% male). There were 88.2% mild, 3.92% moderate, and 7.84% severe cases of AP in the 5-ASA-DIAP group, and 70.6%, 25.5%, and 3.92% such cases in the CAP population, respectively. Symptoms improved significantly faster (mean ± SE, 2.5 ± 0.34 vs 3.74 ± 0.42 days; P = 0.018); however, pancreatic enzyme levels normalized significantly more slowly (6.27 ± 1.53 vs 3.63 ± 0.61 days, P = 0.008) in the 5-ASA-DIAP cohort compared with the CAP group. This study confirms that there are no diagnostic differences between 5-ASA-DIAP and AP of other etiologies. CONCLUSIONS: Fewer moderate but more severe cases were found in the 5-ASA-DIAP group; therefore, 5-ASA-DIAP must be taken as seriously as AP of other etiologies.


Assuntos
Mesalamina/efeitos adversos , Pâncreas/efeitos dos fármacos , Pancreatite/diagnóstico , Índice de Gravidade de Doença , Doença Aguda , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Criança , Feminino , Humanos , Masculino , Mesalamina/química , Pessoa de Meia-Idade , Pâncreas/patologia , Pancreatite/induzido quimicamente , Estudos Retrospectivos , Adulto Jovem
11.
Molecules ; 24(7)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959759

RESUMO

Guava (Psidium guajava L., Myrtaceae) leaves have been used as a folk herbal tea to treat diabetes for a long time in Asia and North America. In this study, we isolated polysaccharides from guava leaves (GLP), and evaluated its antioxidant activity in vitro and anti-diabetic effects on diabetic mice induced by streptozotocin combined with high-fat diet. The results indicated that GLP exhibited good DPPH, OH, and ABTS free-radical scavenging abilities, and significantly lowered fasting blood sugar, total cholesterol, total triglycerides, glycated serum protein, creatinine, and malonaldehyde. Meanwhile, it significantly increased the total antioxidant activity and superoxide dismutase (SOD) enzyme activity in diabetic mice, as well as ameliorated the damage of liver, kidney, and pancreas. Thus, polysaccharides from guava leaves could be explored as a potential antioxidant or anti-diabetic agents for functional foods or complementary medicine.


Assuntos
Antioxidantes/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Polissacarídeos/administração & dosagem , Psidium/química , Animais , Antioxidantes/química , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica/efeitos adversos , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/química , Humanos , Insulina/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Pâncreas/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Folhas de Planta/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Superóxido Dismutase/genética
12.
BMC Cancer ; 19(1): 394, 2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31029111

RESUMO

BACKGROUND: Locally advanced pancreatic cancer (LAPC) represents more than one third of pancreatic cancers and owns poor survival after the standard chemotherapy. Irreversible electroporation (IRE) is a novel method and has been recently used in LAPC. The aim of this study was to compare the efficacy of IRE and radiotherapy after induction chemotherapy for patients with LAPC. METHODS: From August 2015 to August 2017, a total of 76 patients with biopsy proven LAPC and who had received IRE or radiotherapy after chemotherapy were included. Thirty-two pairs of patients were selected through propensity score matching (PSM) analysis and the efficacy of two treatments was compared. RESULTS: Before PSM analysis, after induction chemotherapy, patients with LAPC benefited more in terms of overall survival (OS) and progression free survival (PFS) from IRE, compared with radiotherapy (2-year OS rates, 53.5% vs 26.9%, p = 0.039; 2-year PFS rates, 28.4% vs 13.3%, p = 0.045). After PSM analysis, the survival benefits of OS and PFS of patients after induction chemotherapy followed by IRE were more obvious than those of patients treated with radiotherapy (2-year OS rates, 53.5% vs 20.7%, p = 0.011; 2-year PFS rates, 28.4% vs 5.6%, p = 0.004). Multivariate Cox regression analysis indicated that IRE after induction chemotherapy was identified as a significant favourable factor for both OS and PFS in both the whole and matched cohort. CONCLUSIONS: Induction chemotherapy followed by IRE is superior to induction chemotherapy followed by radiotherapy for treating LAPC. A randomized clinical trial comparing the efficacy of IRE and radiotherapy after the induction chemotherapy is therefore considerable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eletroporação/métodos , Neoplasias Pancreáticas/terapia , Radioterapia/métodos , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/efeitos da radiação , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Pontuação de Propensão
13.
Ann Clin Lab Sci ; 49(2): 193-203, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31028064

RESUMO

Our aims were to evaluate N-acetyl-beta-D-glucosaminidase (NAG) activity in an experimental rat model of chronic exposure to cadmium and its response to ozone therapy. Forty male Wistar rats were divided into five groups: control, cadmium only, cadmium and oxygen, cadmium and ozone, and ozone only. Cadmium concentration (ASA method) and NAG activity (by the Maruhn method) were determined in the supernatants of the kidneys, liver, and pancreas. The histopathological alterations were evaluated in tissue sections.The highest concentration of cadmium and NAG activity was observed in rats intoxicated with cadmium. Ozone therapy led to a decrease in cadmium accumulation in the kidneys and liver. An examination of renal, hepatic and pancreatic tissues revealed severe histopathological lesions in Cadmium group (Cd) treated animals. The histopathological changes in animals treated with ozone were similar, but with slightly decreased intensity. Positive correlations between histochemical lesions, NAG activity and cadmium concentration in the study groups were observed. It has been shown that chronic cadmium intoxication has cytotoxic activity in the kidneys, liver, and pancreas, causing an increase in NAG activity. Ozone therapy significantly reduces NAG activity and the severity of histopathological lesions in the kidneys and liver, confirming its beneficial effects.


Assuntos
Acetilglucosaminidase/metabolismo , Cádmio/farmacologia , Ozônio/toxicidade , Animais , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Ratos Wistar , Distribuição Tecidual/efeitos dos fármacos
14.
J Diabetes Res ; 2019: 1649279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30956991

RESUMO

Lacking the initial contact between the immune system and microbial-associated molecular patterns (MAMPs), such as lipopolysaccharides (LPS), early in life, may be regarded as one of the causal factors of the increasing global increase in the incidence of autoimmune diseases, such as type 1 diabetes (T1D). Previously, a reduced incidence of T1D accompanied by dramatically increased abundances of both the mucin-metabolising bacterium Akkermansia muciniphila, and LPS-carrying Proteobacteria was observed, when vancomycin was given to pups of nonobese diabetic (NOD) mice. While the T1D incidence reducing effect of A. muciniphila has been shown in further studies, little is known as to whether the increased abundance of LPS-carrying bacteria also has a protective effect. Therefore, we fed NOD pups with Eschericia coli LPS orally from birth to weaning, which decreased the gene expressions of TNFα, IL-10, IL-6, IFNγ, IL-1ß, IL-2, IL-4, and FoxP3 in the pancreatic lymph nodes, while the same gene expression profile in the spleen was unaffected. However, no significant difference in the incidence of T1D, gut microbiota composition, or ileum expression of the genetic markers of gut permeability, Claudin8, Occludin, Zonulin-1 (Tjp1), Claudin15, Muc1, and Muc2 were observed in relation to LPS ingestion. It is, therefore, concluded that early life oral E. coli LPS has an impact on the local immune response, which, however, did not influence T1D incidence in NOD mice later in life.


Assuntos
Lipopolissacarídeos/administração & dosagem , Linfonodos/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Administração Oral , Animais , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/imunologia , Esquema de Medicação , Escherichia coli , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Incidência , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Pâncreas/imunologia
15.
Molecules ; 24(5)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818888

RESUMO

Curcumin (CC) is known to have anti-inflammatory and anti-oxidative properties and has already been tested for its efficiency in different diseases including diabetes mellitus (DM). New formulations and route administration were designed to obtain products with higher bioavailability. Our study aimed to test the effect of intraperitoneal (i.p.) administration of liposomal curcumin (lCC) as pre-treatment in streptozotocin(STZ)-induced DM in rats on oxidative stress, liver, and pancreatic functional parameters. Forty-two Wistar-Bratislava rats were randomly divided into six groups (seven animals/group): control (no diabetes), control-STZ (STZ-induced DM -60 mg/100g body weight a single dose intraperitoneal administration, and no CC pre-treatment), two groups with DM and CC pre-treatment (1mg/100g bw-STZ + CC1, 2 mg/100g bw-STZ + CC2), and two groups with DM and lCC pre-treatment (1 mg/100g bw-STZ + lCC1, 2 mg/100g bw-STZ + lCC1). Intraperitoneal administration of Curcumin in diabetic rats showed a significant reduction of nitric oxide, malondialdehyde, total oxidative stress, and catalase for both evaluated formulations (CC and lCC) compared to control group (p < 0.005), with higher efficacy of lCC formulation compared to CC solution (p < 0.002, excepting catalase for STZ + CC2vs. STZ + lCC1when p = 0.0845). The CC and lCC showed hepatoprotective and hypoglycemic effects, a decrease in oxidative stress and improvement in anti-oxidative capacity status against STZ-induced DM in rats (p < 0.002). The lCC also proved better efficacy on MMP-2, and -9 plasma levels as compared to CC (p < 0.003, excepting STZ + CC2 vs. STZ + lCC1 comparison with p = 0.0553). The lCC demonstrated significantly better efficacy as compared to curcumin solution on all serum levels of the investigated markers, sustaining its possible use as adjuvant therapy in DM.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lipossomos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Curcumina/administração & dosagem , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Hipoglicemiantes/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Ratos , Ratos Wistar
16.
Eur J Med Chem ; 170: 28-44, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878830

RESUMO

Pancreatic cancer is one of the most deadly neoplasm with a 5-year survival rate of less than 6% owing to its remarkable tolerance to nutrient starvation, and new drugs and treatment strategies are urgently needed. During a project aiming at discovery of anticancer agents, we performed a structure modification on polycyclic polyprenylated acylphloroglucinols (PPAPs) skeleton, and discovered that PPAP rearranged to a tetrahydroquinolin-2(1H)-one feature. Here, series of tetrahydroquinolin-2(1H)-one derivatives were designed, synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (PANC-1), and the structure-activity relationship was also discussed. Among them, derivative 11k showed the most potent inhibitory activity with an IC50 value of 4.9 µM under nutrient-deprived condition. In contrast, all these derivatives exhibited low cytotoxicity against PANC-1 cells under normal nutrient condition, suggesting that the derivatives appeared to allow alternative tumor cell death mechanisms, and led to less toxicity. Further evaluations demonstrated that 11k decreased colony formation and induced the apoptosis of PANC-1 under nutrient-deprived condition in a concentration dependent manner. In in vivo study, 11k significantly suppressed the tumor development and weight in nude mice. Preliminary mechanism research revealed that 11k clearly downregulated LC3-II expression and increased the level of p62, two key autophagy markers and critical signals for pancreatic tumor growth and progression. Our current findings demonstrated that 11k might be a promising candidate for the new chemotherapeutic molecule of pancreatic cancer, and deserve further study.


Assuntos
Antineoplásicos/química , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Quinolinas/química , Quinolinas/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos Nus , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Quinolinas/síntese química , Quinolinas/farmacologia
17.
Biomed Pharmacother ; 113: 108702, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844658

RESUMO

Rhinacanthus nasutus has traditionally been used in the treatment of various disorders including diabetes mellitus. Rhinacanthins-rich extract (RRE) is a semipurified R. nasutus leaf extract that contains 60% w/w of rhinacanthin-C (RC) obtained by a green extraction process. The purpose of this study was to investigate the anti-hyperglycemic and anti-hyperlipidemic activity of RRE (15 mg/kg equivalent to RC content) in comparison to its marker compound RC (15 mg/kg) and the standard drug glibenclamide (Glb) (600 µg/kg) in nicotinamide-streptozotocin induced diabetic rats for 28 days. In addition, the in silico pharmacokinetic and toxicity analysis of RC was also performed. RRE, RC and Glb significantly reduced the FBG, HbA1c and food/water intake while increasing the insulin level and body weight in diabetic rats without affecting the normal rats. The serum lipid, liver and kidney biomarkers were markedly normalized by RRE, RC and Glb in diabetic rats without affecting the normal rats. Moreover, the histopathology of the pancreas revealed that RRE, RC and Glb evidently restored the islets of Langerhans in diabetic rats. The overall results indicated that RRE has equivalent antidiabetic potential to that of RC. Moreover, the in silico pharmacokinetic and toxicity analysis predicts that RC is orally non-toxic, non-carcinogenic and non-mutagenic with a decent bioavailability. The undertaken study suggests that RRE could be used as an effective natural remedy in the treatment of diabetes.


Assuntos
Acanthaceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Naftoquinonas/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Simulação por Computador , Diabetes Mellitus Experimental/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Hemoglobina A Glicada/análise , Química Verde , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/toxicidade , Hipolipemiantes/farmacocinética , Hipolipemiantes/toxicidade , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Naftoquinonas/farmacocinética , Naftoquinonas/toxicidade , Niacinamida , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Extratos Vegetais/farmacocinética , Folhas de Planta/química , Ratos Wistar , Estreptozocina
18.
Ann Endocrinol (Paris) ; 80(2): 128-133, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30833018

RESUMO

In the modern world, type-2 diabetes mellitus has become a leading public healthcare problem, due to major risks of morbidity and mortality. Prevalence has increased significantly in recent decades. Treatment involves oral hypoglycemic agents or insulin replacement therapy. Development is ongoing for cell-based diabetes therapies using stem cells with the potential to differentiate into insulin-producing cells (IPCs): embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and stem cells from adult pancreas, liver, central nervous system, bone marrow and adipose tissue. Successful induction of iPSCs, however, depends on the quantity and quality of available stem cells and the development of adapted protocols determining the environment of extrinsic factors and involvement of small molecules. Validating such new cell therapies must be founded on this experimental rationale.


Assuntos
Fatores Biológicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células-Tronco Pluripotentes/efeitos dos fármacos , Animais , Fatores Biológicos/análise , Fatores Biológicos/isolamento & purificação , Técnicas de Cultura de Células , Reprogramação Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Pâncreas/citologia , Pâncreas/efeitos dos fármacos , Pâncreas/fisiologia , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/fisiologia , Bibliotecas de Moléculas Pequenas/análise
19.
J Ethnopharmacol ; 237: 159-170, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30902747

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Raffia palm (Raphia hookeri) wine (RPW) is amongst the natural products from plants, utilized singly or in combination with other medicinal plants for the treatment of several ailments including Diabetes Mellitus (DM). However, there is a scientific dearth on its antidiabetic activity. AIM: The antidiabetic effect of RPW and its possible mechanism of actions were investigated in diabetic rats. METHODS: Four groups of male SD rats were first supplied with 10% fructose solution ad libitum for 2 weeks instead of drinking water followed by an intraperitonial injection of streptozotocin (40 mg/kg) to induce diabetes. Two diabetic groups were administered RPW at 150 and 300 mg/kg bodyweight (BW) respectively; a group was administered with metformin, while the other one was served as a negative control. Two groups of normal rats were administered with water and RPW (300 mg/kg BW) and served as normal control and normal toxicology group, respectively. RESULTS: Five weeks treatment of RPW led to significant (p < 0.05) increase in serum insulin and HDL-c levels with concomitant reduction in blood glucose, fructosamine, ALT, uric acid, triglycerides and LDL-c levels in diabetic rats. Rats treated with RPW had elevated levels of GSH, SOD, catalase, ATPase and α-amylase activities, while reduced NO level and myeloperoxidase activity was observed in their serum and pancreatic tissues. RPW also improved pancreatic ß-cell function and restored ß- and acinar cells morphology, and capillary networks. The activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose-6-phosphatase, and acetylcholinesterase were also inhibited in RPW-treated diabetic rats, with concomitant down regulation of Nrf2 gene expression. CONCLUSION: The data of this study suggest that RPW modulates glucose homeostasis by enhancing insulin secretion as well as inhibiting redox imbalance in diabetic rats, which may be attributed to the synergetic effects of its phytochemical constituents as identified by GC-MS analysis.


Assuntos
Arecaceae , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Vinho , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Frutose , Secreção de Insulina/efeitos dos fármacos , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Ratos Sprague-Dawley , Estreptozocina
20.
J Cancer Res Ther ; 15(1): 231-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880783

RESUMO

Aim: The effect of acetylsalicylic acid (ASA) on thiol levels was studied in a rat model of azaserine carcinogenesis. Materials and Methods: ASA and azaserine were applied to the animals to research changes in cellular sulfhydryl (-SH) content and variations in free and protein-bound molecules containing the -SH group. Such effects in rats injected with azaserine were investigated at low (200 ppm) and high (400 ppm) concentrations of ASA over a relatively short (6 months) and a relatively long (12 months) period. Results: Changes in the hepatic, pancreatic, and renal -SH contents were also determined. Conclusion: Compared to the other tissues studied, the liver contained the highest levels of both free and protein-bound -SH.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Azasserina/toxicidade , Carcinógenos/toxicidade , Neoplasias/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Humanos , Rim/química , Rim/efeitos dos fármacos , Rim/patologia , Fígado/química , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Neoplasias/induzido quimicamente , Neoplasias/patologia , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Pâncreas/química , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Ratos , Ratos Wistar , Compostos de Sulfidrila/análise , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA