RESUMO
Metformin is the first line drug in the treatment of type 2 diabetes, however, little is known about its therapeutic potential to prevent or delay damage to the peripheral nerve. Thus, the aim of this study was to investigate whether metformin is able to attenuate the neuroinflammatory response in sciatic nerve of insulin-dependent diabetic mice. Swiss Webster mice were divided into four groups: Control, Diabetic (STZ), Diabetic +100â¯mg/kg/day of metformin (STZâ¯+â¯M100) and Diabetic +200â¯mg/kg/day of metformin. Diabetes was induced by streptozotocin (90â¯mg/kg, i.p.). Only animals with glycemia ≥270â¯mg/dl were considered diabetics. Metformin prevented atrophy of myelinated axons, and reduced expression of inflammatory mediators (interleukin-1ß, inducible nitric oxide synthase and nitric oxide). However, treatment with 200â¯mg of metformin was more effective in increasing neurotrophic (myelin basic protein and neural growth factor), angiogenic (vascular endothelial growth factor) and anti-inflammatory (inhibitor kappa B-alpha and interleukin 10) factors. Thus, metformin treatment, especially at the dose of 200â¯mg, protected the nerve from damages related to chronic hyperglycemia.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Camundongos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismoRESUMO
BACKGROUND AND AIM: While diethylcarbamazine citrate (DEC) displays important anti-inflammatory effects in experimental models of liver injury, the mechanisms of its action remain poorly understood. The aim of the present study was to investigate the fibrolytic potential of DEC. METHODS: Mice receive two injections of carbon tetrachloride (CCl4) per week for 8 weeks. DEC 50 mg/kg body weight was administered through drinking water during the last 12 days of liver injury. RESULTS: The expression of hepatic stellate cells (HSCs) activation markers, including smooth muscle α-actin (α-SMA), collagen I, transforming growth factor-ß 1 (TGF-ß1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was assessed. The influence of DEC on the intracellular MAPK pathways of the HSCs (JNK and p38 MAPK) was also estimated. DEC inhibited HSCs activation measured as the production of α-SMA and collagen I. In addition, it down regulated the production of TGF-ß1 and TIMP-1, and concomitantly increased MMP-2 activity. Furthermore, DEC significantly inhibited the activation of the JNK and p38 MAPK signaling pathways. CONCLUSIONS: In conclusion, DEC significantly attenuated the severity of CCl4-induced liver injury and the progression of liver fibrosis, exerting a potential fibrolytic effect in the CCl4-induced fibrosis model.
Assuntos
Biomarcadores/metabolismo , Tetracloreto de Carbono/farmacologia , Dietilcarbamazina/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Actinas/metabolismo , Animais , Colágeno Tipo I/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The aim of this study was to investigate the antimicrobial activity of different extracts and fractions obtained from Hymenaea stigonocarpa stem barks. The cyclohexanic, ethyl acetate, ethanol, aqueous, and hydroalcoholic extracts were obtained by maceration. The hydroalcoholic extract was partitioned, which resulted in the ethyl acetate and aqueous fractions. All extracts and fractions were subjected to phytochemical screening and evaluation of total phenol and tannin contents. An HPLC-DAD and ultrastructural alterations analysis were performed. Terpenes and coumarins were detected in the cyclohexanic extract. Flavonoids and condensed tannins were present in the other extracts and fractions. The extracts with the highest contents of tannins, ethanol (EE), hydroalcoholic (HE), and aqueous fraction (AF) showed also the highest antimicrobial activity. The MIC values ranged from 64 to 526 µg/mL. The chromatographic fingerprints suggest the presence of astilbin and other flavonoids in EE and HE. Presence of the thick cell wall, undulating outer layer, abnormal septa, and leakage of the cytoplasmic contents and absence of cell wall and cell lyses were the main alterations observed on Staphylococcus aureus ATCC 33591 after treatment with the Hymenaea stigonocarpa hydroalcoholic extract. The presence of phenolic compounds like flavonoids and tannins is possibly the reason for the antimicrobial activity.