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1.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361786

RESUMO

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.


Assuntos
Antioxidantes/farmacologia , Betula/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Acetaldeído/antagonistas & inibidores , Acetaldeído/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Betula/classificação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Malondialdeído/antagonistas & inibidores , Camundongos , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Casca de Planta/classificação , Extratos Vegetais/química , Polônia , Superóxidos/antagonistas & inibidores , Triterpenos/química , Triterpenos/isolamento & purificação
2.
Acta Biochim Pol ; 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314132

RESUMO

Matrix metalloproteinases (MMPs) play an important role in many physiological and pathological processes, including neoplastic processes. They belong to a group of enzymes called endopeptidases and have the ability to hydrolyze all proteins in the extracellular matrix (ECM). They are produced in most connective tissue cells, macrophages, leukocytes, endothelial cells, microglial cells and in cancer cells. Neoplastic diseases are one of the main causes of death in Poland and in the world, therefore learning about the process of carcinogenesis seems to be particularly important. The process of carcinogenesis is currently widely studied and MMPs play one of the key roles in the development of cancer. They do this by regulating local tumor growth, stromal invasion, stimulating angiogenesis and metastasis formation. Bladder cancer is the 7th most common cancer in the male population and the 11th most common cancer in the world. In bladder cancer, most studies have been devoted to MMP-2 and MMP-9, that are enzymes responsible for the degradation of type IV collagen in the first place, which through the destruction of basement membranes and ECM, play an essential role in the tumor invasion process. Since bladder cancer is characterized by the ability to relapse, from the point of view of clinical practice it seems particularly important to develop a marker of early bladder tumor recurrence. MMPs detected in the urine and serum of patients with bladder cancer are potential factors that could play such a role.

3.
Pestic Biochem Physiol ; 174: 104812, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33838712

RESUMO

Skin acts as a mechanical barrier between human body and environment. Epidermal cells are regularly exposed to many physiological and environmental stressors, such as pesticides, like chlorpyrifos (CPS). It is recognised that CPS may affect metabolism of other exo- and endogenous substances by affecting enzyme activity and expression. This study aims to investigate the effect of CPS on expression of CYP27A1, CYP27B1 and CYP24A1, the enzymes involved in synthesis and metabolism of vitamin D3, in human keratinocytes HaCaT and human fibroblasts BJ. Synthesis of vitamin D3 in cells was initiated by irradiating with UVB. Expression of CYP27A1, CYP27B1 and CYP24A1 was evaluated by RT-qPCR and Western blot. Our experiments revealed that expression of all tested cytochrome P450 isoforms in cells exposed to CPS changed significantly. Exposure of HaCaT keratinocytes to CPS decreased CYP27A1 mRNA levels, but increased CYP27B1 and CYP24A1 mRNA levels. This was confirmed at the protein level, except for the CYP27A1 expression. Outcome for the BJ cells was however less conclusive. Though exposure to CPS decreased CYP27A1 and CYP27B1 mRNA levels, at protein level increasing concentration of CPS and UVB intensity induced expression of CYP27A1 and CYP24A1. The expression of CYP27B1 isoform decreased in line with mRNA level. Nevertheless, it can be concluded that CPS may therefore interrupt vitamin D3 metabolism in skin cells, but further studies are required to better understand such mechanisms.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase , Clorpirifos , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Clorpirifos/toxicidade , Colecalciferol , Pele , Vitamina D , Vitamina D3 24-Hidroxilase/genética
4.
Ir J Med Sci ; 190(1): 255-259, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32594304

RESUMO

BACKGROUND: Increased blood pressure in the varicose veins (VV) can contribute to the overexpression of matrix metalloproteinases (MMPs), affecting the endothelium, smooth muscle, and extracellular matrix of the vein wall. Gelatinases (MMP-2 and MMP-9), hypoxia, and inflammation occurring in the VV wall contribute to the increased expression of vascular endothelial growth factor (VEGF). AIMS: Our objective was to analyze the concentration of gelatinases and VEGF in the great saphenous VV wall and plasma of patients. METHODS: In total, 65 patients (2nd degree according to clinical state classification, etiology, anatomy, and pathophysiology-CEAP classification) aged 22 to 70 were enrolled. Control veins (n = 10) were collected from the patients who underwent coronary artery bypass graft surgery. Control plasma (n = 20) was obtained from healthy individuals. Gelatinases and VEGF levels were measured with the usage of ELISA method. RESULTS: A significant increase in MMP-9 (11.2 vs. 9.98 ng/mg of protein) and VEGF (41.06 vs. 26 ng/g of protein) concentration in VV wall compared with control veins was observed. A positive correlation between VEGF versus MMP-2 (p = 0.03, r = 0.27) was found in the VV wall. However, no correlation was found between the concentration of VEGF and MMP-9 (p = 0.4, r = 0.11) in the VV wall. In addition, no statistical differences between MMP-9, MMP-2, and VEGF levels in plasma of VV patients compared with controls were noticed. CONCLUSIONS: The results of the present study confirm that VV's patients have altered expression of MMPs and VEGF. Overexpression of MMP-9 and VEGF in the VV wall may contribute to the spreading of inflammatory process and suggests the intense remodeling of extracellular tissue within the VV wall.


Assuntos
Matriz Extracelular/metabolismo , Gelatinases/metabolismo , Varizes/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Front Neurosci ; 14: 730, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903765

RESUMO

Bergapten is a furanocoumarin naturally occurring in the Apiaceae family and it is a well-known photosensitizing agent used in photochemotherapy. In this study, we investigated the influence of bergapten on cognitive function and mechanism underlying these effects in scopolamine-induced memory impairment in male Swiss mice. The passive avoidance test was used to evaluate the efficiency of memory acquisition and consolidation. The results demonstrated that both single and repeated administration of bergapten improved not only the acquisition but also consolidation of memory. The behavioral tests showed that bergapten prevented memory impairment induced by administration of scopolamine. Observed effects may result from the inhibition of acetylcholinesterase activity in the hippocampus and prefrontal cortex. Also, bergapten caused significant anti-oxidative effects. These new findings provide pharmacological and biochemical support for the development of the coumarin's potential in cognitive deficits.

6.
Oxid Med Cell Longev ; 2020: 7140496, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908636

RESUMO

In an infant's body, all the systems undergo significant changes in order to adapt to the new, extrauterine environment and challenges which it poses. Fragile homeostasis can be easily disrupted as the defensive mechanisms are yet imperfect. The activity of antioxidant enzymes, i.e., superoxide dismutase, catalase, and glutathione peroxidase, is low; therefore, neonates are especially vulnerable to oxidative stress. Free radical burden significantly contributes to neonatal illnesses such as sepsis, retinopathy of premature, necrotizing enterocolitis, bronchopulmonary dysplasia, or leukomalacia. However, newborns have an important ally-an inducible heme oxygenase-1 (HO-1) which expression rises rapidly in response to stress stimuli. HO-1 activity leads to production of carbon monoxide (CO), free iron ion, and biliverdin; the latter is promptly reduced to bilirubin. Although CO and bilirubin used to be considered noxious by-products, new interesting properties of those compounds are being revealed. Bilirubin proved to be an efficient free radicals scavenger and modulator of immune responses. CO affects a vast range of processes such as vasodilatation, platelet aggregation, and inflammatory reactions. Recently, developed nanoparticles consisting of PEGylated bilirubin as well as several kinds of molecules releasing CO have been successfully tested on animal models of inflammatory diseases. This paper focuses on the role of heme metabolites and their potential utility in prevention and treatment of neonatal diseases.


Assuntos
Bilirrubina/metabolismo , Monóxido de Carbono/metabolismo , Heme/metabolismo , Doenças do Recém-Nascido/metabolismo , Humanos , Recém-Nascido , Doenças do Recém-Nascido/terapia , Inflamação/complicações , Inflamação/patologia , Espécies Reativas de Oxigênio/metabolismo
7.
Ann Agric Environ Med ; 27(2): 290-294, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32588608

RESUMO

OBJECTIVE: The aim of this study is to evaluate neurological scales, as well as biochemical and radiological parameters measured on day 10 after ischemic stroke (IS), according to their value as predictors of the long-term outcome. MATERIAL AND METHODS: 45 patients were assessed according to the Barthel Index (BI) and National Institute of Health Stroke Scale (NIHSS) on day 10, and according to Modified Rankin Scale (mRS) 3 months after the onset of IS. On day 10 of IS, the serum level of C-reactive protein (CRP), albumin, D-dimers (DD), S100BB and Tau proteins was measured and the volume of ischemic focus assessed with the use of Computed Tomography (CT). The patients were divided into groups with good outcome (GO) and mRS 0-2, and with bad outcome (BO) and mRS 3-6. RESULTS: NIHSS and BI scores (p<0.001), the volume of ischemic focus (p<0.01), CRP (p<0.01) and albumin level (p<0.05), but not DD, S100BB and Tau protein levels evaluated on day 10, correlated with mRS after 3 months since IS onset. Patients from the BO group were observed to have lower BI (p=0.001), higher NIHSS (p<0.01) and CRP levels (p<0.05), and bigger volume of ischemic focus (p<0.05) measured on day 10 of IS. In the GO group, there were more patients with atherosclerotic etiology (p=0.02 x2=7.856). Regression analysis showed that only the BI score assessed on day 10 of IS can predict the outcome after 3 months assessed by mRS (OR=1.102, 95%, CI:1.01-1.203; p=0.001). CONCLUSIONS: BI assessed on day 10 has a predictive value for the outcome evaluated by mRS 3 months after the onset of IS.


Assuntos
Isquemia Encefálica/terapia , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Análise Química do Sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Prognóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Ann Agric Environ Med ; 27(1): 129-133, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32208591

RESUMO

INTRODUCTION: Lithium has been used in medicine for almost seventy years. Besides beneficial effects, its therapy may cause serious side-effects, with kidney and liver being the organs most vulnerable to its harmful influence. Therefore, research on protective agents against lithium toxicity has been continuing for some time. OBJECTIVE: The aim of the present study is to evaluate the influence of additional selenium supplementation on lithium content, as well as homeostasis of the essential microelements iron, zinc, copper and manganese in kidney and liver of rats undergoing lithium exposure. MATERIAL AND METHODS: The study was performed on 4 groups of male Wistar rats (6 animals each) treated with: control - saline; Li-group - Li2CO3 at a dose of 2.7 mg Li/kg b.w.; Se-group - Na2SeO3 at a dose of 0.5 mg Se/kg b.w.; Li+Se-group - both Li2CO3 and Na2SeO3 at doses of 2.7 mg Li/kg b.w. and of 0.5 mg Se/kg b.w., respectively, in the form of water solutions by stomach tube, once a day for 3 weeks. The content of the studied elements in the organ samples was determined using flame atomic absorption spectroscopy (FAAS). RESULTS: Lithium administered alone caused a significant increase in its content in liver and kidney. Additional supplementation with selenium reversed these effects, and did not markedly affect other studied microelements compared to control. CONCLUSIONS: The obtained results suggest that selenium could be regarded as an adjuvant into lithium therapy. However, considering the limitations of the present study (the short duration, using only one dose and form of selenium) the continuation of the research seems to be necessary to clarify the influence of selenium supplementation on basic microelements and lithium accumulation in organs during lithium exposure.


Assuntos
Carbonato de Lítio/toxicidade , Selênio/farmacologia , Oligoelementos/metabolismo , Animais , Homeostase/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Carbonato de Lítio/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar , Oligoelementos/antagonistas & inibidores
9.
J Neurosurg Sci ; 64(5): 452-455, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28945050

RESUMO

BACKGROUND: Nitric oxide (NO) is synthesized by the conversion of Arginine (Arg) into the NO and Citrulline (Cit). Although the NO is involved into the pathogenesis of several physiological and pathological processes, the role of NO in pituitary adenomas (PA) progression is not determined. Our purpose was to evaluate the relationship between NO and PA as well as the effect of tumor resection on NO metabolites level in serum. METHODS: The study group consisted of 21 patients with PA, 18 patients with macroadenomas and 3 with microadenomas. Venous blood samples were collected at two time-points; 1) before the surgery and 2) 3-5 days after PA resection. Arg and Cit levels were determined by the automated ion-exchange chromatography with usage of Amino Acids Analyser (AAA 400). Commercially available kit for the evaluation of nitrate/nitrite serum levels was applied for indirect assessment of serum NO level. RESULTS: Significant decrease in NO concentration after the surgery was observed in comparison with the time-point 1. Arg level did not significantly change during the study period. Cit level was ranged below the detection limit of applied method. CONCLUSIONS: The decrease of NO level after the pituitary adenoma resection indicates the relationship between NO synthesis and PA occurrence.

10.
J Pain Res ; 12: 1457-1464, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190955

RESUMO

Purpose: The aim of our research was to investigate the link between serum levels of metalloproteinase-2 (MMP-2) and MMP-9, and the degree of pain experienced before and 1 and 3 months after microdiscectomy in 70 patients with disc herniation (DH). Patients and methods: The control group (group C) consisted of 70 healthy subjects and the DH group consisted of 70 patients with sciatica pain caused by lumbar DH. Before (DH0) and 1 and 3 months after surgery, the patients were assessed in terms of the following biochemical parameters: MMP-2, tissue inhibitors of metalloproteinases-2 (TIMP-2), MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP1, and the following clinical parameters: Numeric Rating Scale for the back (NRS-B) and the leg (NRS-L) and the Pain Rating Index (PRI) and Present Pain Intensity (PPI) of the McGill Pain Questionnaire. Results: No statistically significant correlations were observed following the biochemical and clinical assessments performed in group C and the DH group before surgery. After surgery (1 month), higher levels of TIMP-1 correlated with higher levels of NRS-B (rs =0.27; p<0.05). At 3 months after surgery higher levels of TIMP-2 and lower levels of MMP-2/TIMP-2 were correlated with higher levels of NRS-L (rs =0.27, p<0.05 and rs =-0.31, p<0.05, respectively) and higher levels of TIMP-2 were correlated with higher PRI scores (rs =0.27; p<0.005) and PPI scores (rs =0.35; p<0.01). Conclusion: The results showed that MMPs are involved in DH and play a significant role in the perception of pain after DH surgery. However, the value of MMPs as a potential therapeutic target in pain treatment should be considered cautiously.

11.
Medicina (Kaunas) ; 55(5)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100974

RESUMO

Background and Objective: Osteoarthritis (OA) is a disorder of the musculoskeletal system resulting in worsening of life condition. The research revealed the involvement of oxidative stress into both OA pathogenesis and the effects of therapeutic agents applied in OA cases. The activities of the most important antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant status (TAS), in blood of the knee OA patients were studied, with the aim of clarifying which enzymatic antioxidants are involved into osteoarthritis (OA)-related oxidative stress and whether any compensatory effects occur. The results were additionally analyzed with regard to gender. Methods: Whole blood SOD (U/mL), plasma GPx (U/L) and CAT (U/mL) activities as well as plasma TAS (mmol/L)) in knee OA patients were investigated. Sixty-seven patients (49 females and 18 males) with primary knee OA were enrolled. The control comprised 21 subjects (10 females and 11 males) free of osteoarthritis or inflammation. Results: TAS was decreased in OA subjects (4.39 0.53 vs. 4.70 0.60), with this effect being more significant in OA females (4.31 0.51 vs. 5.02 0.54). GPx was depressed in all OA patients (518 176 vs. 675 149). In both genders, GPx was decreased, significantly in males (482 185 vs. 715 105). SOD was decreased in all OA patients (109 32 vs. 127 42). CAT showed no difference in all OA subjects vs. control, while in OA females it was depleted (20.2 (11.6-31.6) vs. 38.5 (27.9-46.6)) and in OA men it increased (26.9 (23.3-46.5) vs. 14.0 (7.0-18.6)). Conclusions: The obtained results suggest that in men some compensatory mechanisms towards OA-related oxidative stress occurred. Based on the obtained data, the introduction of antioxidant supplements into OA therapy could be suggested with further research concerning the choice of agents.


Assuntos
Osteoartrite do Joelho/fisiopatologia , Estresse Oxidativo/fisiologia , Catalase/análise , Progressão da Doença , Feminino , Glutationa Peroxidase/análise , Humanos , Articulação do Joelho/enzimologia , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Superóxido Dismutase/análise
12.
Ann Agric Environ Med ; 26(1): 97-102, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30922037

RESUMO

INTRODUCTION AND OBJECTIVE: Osteoarthrits (OA) is a complex, chronic disorder of cartilage and bone, related to homeostasis of bioelements. The current study aimed at evaluation of correlations between plasma silicon, magnesium and ionized calcium in OA patients in consideration to gender. MATERIAL AND METHODS: The study comprised 59 patients aged 69.5±9.0 years (18 males aged 66.8±9.2; 41 females aged 70.7±8.8), admitted to the Trauma and Orthopaedic Ward of the Independent Public Health Care Centre in Leczna, Poland, due to OA and qualified to surgery. Control group consisted of 19 subjects without OA (54.5±8.6 years; 10 males aged 41.3±9.3; 9 females aged 69.1±14.9). Plasma concentrations of silicon and magnesium (spectrophotometric methods) and ionized calcium (potentiometric method) were determined. RESULTS: Silicon in OA patients was significantly increased vs. control. In OA males and OA females, silicon was enhanced vs. the respective controls, but it was statistically significant only in males. Magnesium in OA patients was not significantly different from control group. In females, a significant decrease vs. the respective control was observed. No significant differences were observed in the case of ionized calcium. Positive correlations between silicon and magnesium in healthy control, both in the whole group and in male and female subgroups, were noted, while no such effect was observed in OA subjects. CONCLUSIONS: The results might suggest some connection between higher OA incidence in women and the depleted magnesium in the organism. Silicon increase in OA patients, especially in men, may indicate its intense metabolism during the articular inflammatory process, likely dependent on sex hormones. It remains open whether the plasma Si increase is the effect or cause of OA.


Assuntos
Cálcio/sangue , Magnésio/sangue , Osteoartrite do Joelho/sangue , Silício/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/metabolismo , Fatores Sexuais
13.
Neuromodulation ; 22(3): 262-268, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30620420

RESUMO

OBJECTIVES: The impact of spinal cord stimulation (SCS) on serum levels of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was assessed in a group of patients with failed back surgery syndrome (FBSS). The study was to give new insights into the SCS mechanism of action and the role of MMP-2 and MMP-9 in the development of NP. MATERIAL AND METHODS: Clinical assessments were performed and biochemical markers were determined in two groups of patients: the control group (24 individuals) and the FBSS group (24 patients). Seventeen patients with the FBSS had SCS implanted and were examined before surgical procedure, one month after (17 patients), and three months after operation (12 patients). Clinical status was assessed with the use numeric rating scale, pain rating index of McGill pain questionnaire, Oswestry disability index and Beck depression inventory. MMP-2 and MMP-9 serum levels were determined using gelatin zymography. Immunoenzymatic method was employed to determine plasma concentrations of tissue inhibitors of metalloproteinases (TIMPs). RESULTS: Levels of MMP-2 and TIMP-2 were higher in the FBSS group compared to the control group. The difference was statistically significant (p < 0.001 and p = 0.004, respectively). The concentration of MMP-2 was significantly increased (p = 0.0135) one-month post-SCS and remained elevated but stable up to three months after implantation. TIMP-2, MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP-1 serum levels did not change significantly. CONCLUSIONS: MMPs may play a role in the development of FBSS. SCS increases the already elevated MMP-2 serum levels which are associated with neuroinflammatory processes in FBSS patients.


Assuntos
Síndrome Pós-Laminectomia/sangue , Síndrome Pós-Laminectomia/terapia , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Estimulação da Medula Espinal/tendências , Adulto , Idoso , Biomarcadores/sangue , Eletrodos Implantados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Estudos Prospectivos , Estimulação da Medula Espinal/métodos
14.
Curr Mol Pharmacol ; 12(2): 115-121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30648530

RESUMO

BACKGROUND: The use of drugs of addiction, as mephedrone, is associated with functional neuronal disorders due to remodeling of the nervous tissue. Key enzymes in remodeling are extracellular matrix (ECM) proteases like matrix metalloproteases (MMPs). Recently, MMPs have been of great interest as some studies point to a fact that the alterations in structural remodeling of synaptic connections modify learning-dependent changes, which remain active even after a prolonged period of abstinence. This entails a continuous development of dependence. OBJECTIVES: The aim of the study was to determine the influence of subchronic exposure to three different doses of mephedrone on the activity of MMP-2 and 9 in hippocampus and prefrontal cortex and how this was correlated with memory processes in mice. METHODS: The homogenates of hippocampus and cortex were assayed for MMP-2 and MMP-9 activity by gelatin zymography. Memory consolidation processes were evaluated in the passive avoidance (PA) test. RESULTS: The study confirmed the dose-dependent increase in activity of MMP-2 and -9 exerted by subchronic administration of mephedrone. Moreover, the highest dose of mephedrone attenuated consolidation of memory and learning processes. CONCLUSIONS: We could hypothesize that inhibition of MMPs can be considered as a therapeutic option for the treatment of addictive behaviors associated with cognitive processes. Moreover, further studies are required to find out if elevated activities of MMPs contribute to brain damage or recovery from brain damage caused directly by mephedrone.


Assuntos
Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Memória/efeitos dos fármacos , Metanfetamina/análogos & derivados , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Metanfetamina/toxicidade , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo
15.
Curr Med Chem ; 26(18): 3208-3224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29756562

RESUMO

Matrix metalloproteinases (MMPs) play a key role in remodeling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation, and survival. Their importance in a variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain but only some pathological ones. Numerous neurodegenerative diseases are a consequence of or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development of these diseases. In the present review, we discuss the role of metalloproteinase inhibitors, from the wellknown natural endogenous tissue inhibitors of metalloproteinases (TIMPs) to the exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplastic diseases, the knowledge about the enzymatic system in mammalian brain tissue still remains poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of the physiological function of the adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries, and others.


Assuntos
Doenças do Sistema Nervoso Central/tratamento farmacológico , Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Descoberta de Drogas/métodos , Humanos , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Inibidores de Metaloproteinases de Matriz/uso terapêutico
16.
Pharmacol Rep ; 70(6): 1168-1172, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30321806

RESUMO

BACKGROUND: Selenium is an essential element which shows protective properties against diverse harmful factors. Lithium compounds are widely used in medicine, but, in spite of undoubted beneficial effects, treatment with these compounds may lead to severe side effects, including renal, gastrointestinal, neurological, endocrine and metabolic disorders. This study was aimed at evaluating the influence of selenium and/or lithium on lithium, iron, zinc and copper content in rats' erythrocytes as well as estimate the action of additional selenium on lithium exposure effects. METHODS: The experiment was performed on four groups of rats (six animals each): control - received saline; Li - received 2.7mg Li/kg b.w. as lithium carbonate; Se - received 0.5mg Se/kg b.w. as sodium selenite; Se+Li - received simultaneously 0.5mg Se/kg b.w. and 2.7mg Li/kg b.w. (sodium selenite and lithium carbonate). The administration was performed for three weeks, once a day by stomach tube, in form of water solutions. In erythrocytes the content of lithium, iron, zinc and copper was determined using flame atomic absorption spectroscopy. RESULTS: Lithium treatment insignificantly disturbed iron and zinc homeostasis as well as markedly increased lithium accumulation and copper content in rat erythrocytes. Selenium coadministration reversed those effects. CONCLUSIONS: The beneficial effect of selenium on disturbances of studied microelements homeostasis as well as on preventing lithium accumulation in erythrocytes in Li receiving animals allows suggesting that further research on selenium application as an adjuvant in lithium therapy is worth carrying on.


Assuntos
Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Homeostase/efeitos dos fármacos , Carbonato de Lítio/toxicidade , Selênio/farmacologia , Oligoelementos/metabolismo , Animais , Homeostase/fisiologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Oligoelementos/antagonistas & inibidores
17.
Front Behav Neurosci ; 12: 149, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30116179

RESUMO

3,4-Methylenedioxy-methylamphetamine (MDMA), a synthetic substance commonly known as ecstasy, is a worldwide recreational drug of abuse. As MDMA and nicotine activate the same neuronal pathways, we examined the influence of co-administration of nicotine (0.05 mg/kg) and MDMA (1 mg/kg) on cognitive processes, nicotine-induced behavioral sensitization and on processes linked with oxidative stress and α7 nicotinic acetylcholine receptors (nAChRs) expression in the brain of male Swiss mice. For behavioral study the passive avoidance (PA) test and locomotor sensitization paradigm were used. Also, the oxidative stress parameters as well as expression levels of α7 nAChRs in prefrontal cortex and hippocampus of mice treated with MDMA alone or in combination with nicotine were assessed. The results revealed that MDMA injections as well as co-administrations of MDMA and nicotine improved memory consolidation in male Swiss mice tested in PA task. Furthermore, one of the main findings of the present study is that MDMA increased locomotor activity in nicotine-sensitized mice. Our study showed for the first time strong behavioral and biochemical interactions between nicotine and MDMA. Both drugs are very often used in combination, especially by young people, thus these results may help explaining why psychoactive substances are being co-abused and why this polydrug administration is still a social problem.

19.
Oxid Med Cell Longev ; 2018: 7074209, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854089

RESUMO

Honeybees products comprise of numerous substances, including propolis, bee pollen, and royal jelly, which have long been known for their medicinal and health-promoting properties. Their wide biological effects have been known and used since antiquity. Bee products are considered to be a potential source of natural antioxidants such as flavonoids, phenolic acids, or terpenoids. Nowadays, the still growing concern in natural substances capable of counteracting the effects of oxidative stress underlying the pathogenesis of numerous diseases, such as neurodegenerative disorders, cancer, diabetes, and atherosclerosis, as well as negative effects of different harmful factors and drugs, is being observed. Having regarded the importance of acquiring drugs from natural sources, this review is aimed at updating the current state of knowledge of antioxidant capacity of selected bee products, namely, propolis, bee pollen, and royal jelly, and of their potential antioxidant-related therapeutic applications. Moreover, the particular attention has been attributed to the understanding of the mechanisms underlying antioxidant properties of bee products. The influence of bee species, plant origin, geographic location, and seasonality as well as type of extraction solutions on the composition of bee products extracts were also discussed.


Assuntos
Antioxidantes/metabolismo , Ácidos Graxos/química , Pólen/química , Própole/química , Animais , Abelhas , Ácidos Graxos/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Pólen/metabolismo , Própole/metabolismo
20.
Phlebology ; 33(7): 464-469, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28705052

RESUMO

Objective Our objective was to evaluate the state of oxidative stress in the great saphenous varicose vein wall and blood of varicose vein patients taken from the antecubital vein. Methods The superoxide dismutase, reduced glutathione (GSH) and total antioxidant status were measured with commercially available colorimetric kits in erythrocytes, plasma and varicose vein wall of 65 patients (second degree of clinical state classification, etiology, anatomy and pathophysiology) aged 22-70 (49 women, 16 men) in comparison to normal great saphenous vein walls collected from 10 patients who underwent coronary artery bypass graft and blood collected from 20 healthy individuals. Results A statistically significant decrease (p < 0.001) in superoxide dismutase activity in erythrocytes and the increase (p < 0.05) in superoxide dismutase activity in varicose vein has been observed. There have been no significant changes in the concentration of GSH in plasma and in varicose vein. The decreased concentration of total antioxidant status in plasma (p < 0.001) and in varicose vein wall (p < 0.05) in comparison to the control has been noticed. Conclusion The varicose vein patients are affected by oxidative stress. Our results indicate impaired antioxidant defense mechanism in the blood of varicose vein patients. In contrast to the blood, an increased process of antioxidant defense in the varicose vein wall was noticed.


Assuntos
Antioxidantes/metabolismo , Eritrócitos/metabolismo , Glutationa/sangue , Estresse Oxidativo , Superóxido Dismutase/sangue , Varizes/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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