Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 43
Filter
1.
J Recept Signal Transduct Res ; 37(3): 252-258, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27829319

ABSTRACT

CONTEXT: Tumor cells due to distance from capillary vessels exist in different oxygenation conditions (anoxia, hypoxia, normoxia). Changes in cell oxygenation lead to reactive oxygen species production and oxidative stress. Sigma 1 receptor (Sig1R) is postulated to be stress responding agent and superoxide dismutases (SOD1 and SOD2) are key antioxidant enzymes. It is possible that they participate in tumor cells adaptation to different concentrations of oxygen. OBJECTIVE: Evaluation of Sig1R, SOD1, and SOD2 expression in different concentrations of oxygen (1%, 10%, 21%) in colon adenocarcinoma cell lines. MATERIALS AND METHODS: SW480 (primary adenocarcinoma) and SW620 (metastatic) cell lines were cultured in standard conditions in Dulbecco's modified Eagle's medium for 5 days, and next cultured in Hypoxic Chamber in 1% O2, 10% O2, 21% O2. Number of living cells was determined by trypan blue assay. Level of mRNA for Sig1R, SOD1, and SOD2 was determined by standard PCR method. Statistical analysis was conducted using Statistica 10.1 software. RESULTS: We observed significant changes in expression of Sig1R, SOD1, SOD2 due to different oxygen concentrations. ANOVA analysis revealed significant interactions between studied parameters mainly in hypoxia conditions in SW480 cells and between Sig1R and SOD2 in SW620 cells. It also showed that changes in expression of studied proteins depend significantly on type of the cell line. CONCLUSION: Changes of Sig1R and SOD2 expression point to mitochondria as main organelle responsible for survival of tumor cells exposed to hypoxia or oxidative stress. Studied proteins are involved in intracellular response to stress related with different concentrations of oxygen.


Subject(s)
Adenocarcinoma/genetics , Colonic Neoplasms/genetics , Receptors, sigma/biosynthesis , Superoxide Dismutase-1/biosynthesis , Superoxide Dismutase/biosynthesis , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Antioxidants/metabolism , Cell Line, Tumor , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Humans , Mitochondria/metabolism , Mitochondria/pathology , Oxygen/metabolism , Reactive Oxygen Species/metabolism , Receptors, sigma/genetics , Superoxide Dismutase/genetics , Superoxide Dismutase-1/genetics , Sigma-1 Receptor
2.
Pol Merkur Lekarski ; 40(236): 134-40, 2016 Feb.
Article in Polish | MEDLINE | ID: mdl-27000821

ABSTRACT

Chronic inflammation in the body leads to the formation and development many diseases, e.g. atherosclerosis, diabetes, neurodegenerative diseases or cancer and others. Therefore, the search for new and safe compounds of plant origin having antiinflammatory activity. They include, among others, naturally occurring in the diet of human - flavonoids. Anti-inflammatory effects of these compounds is due to their antioxidant properties, ability to inhibit enzymes involved in the metabolism of eicosanoids and proinflammatory molecules and modulate the expression of certain proinflammatory genes. Intensive studies in vitro and in vivo antiinflammatory activity of flavonoids are important not only because of the knowledge of the mechanisms of action of these compounds, but also to develop a new class of safe anti-inflammatory drugs of plant origin. This should bring prophylactic and therapeutic benefits. A diet rich in flavonoid compounds and/or supplementation with these compounds not only improve the efficiency of prevention of nutrition, but also complement the medical therapy of many diseases.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Flavonoids/pharmacology , Antioxidants/pharmacology , Diet , Dietary Supplements , Humans
3.
Pol Merkur Lekarski ; 38(225): 174-9, 2015 Mar.
Article in Polish | MEDLINE | ID: mdl-25815621

ABSTRACT

The milk fat is characterized by an unique composition (over 400 different fatty acids) and stereospecific structure of triglycerides, similar to human milk fat. Almost entirely it is encircled by envelopes made of phosphorolipids and proteins, making the fat stabile oxidatively and resistant for hydrolysis. The envelope of fatty spherule ensures stability of emulsions, as well, as very high extent of dispersion, making milk fat the most easily digested fat in human diet. Phosphorolipids, proteins, peptides and numerous enzymes present inside the envelope are characterized by very high biological activity. All - without any exception - components of milk fat, also saturated fatty acids considered as atherogenic, are extremely biologically active. Lipophylic antioxidants (conjugated linoleic acid, α-tocopherol, vitamin A and ß-carotene, coenzyme Q10, vitamin D3 and phospholipids) are efficient in inhibition of processes of lipids peroxidation within cell structures and of plasma lipoproteins. The unique components of milk fat i.e. conjugated linoleic acid and ether lipids (alkyloglyceroles and alkyloglycerophospholipids) possess the broadest spectrum of pro-health activity.


Subject(s)
Milk/chemistry , Milk/metabolism , Animals , Antioxidants/analysis , Antioxidants/metabolism , Dietary Fats , Fatty Acids/analysis , Humans , Lipid Peroxidation , Phospholipids/analysis
4.
Pol Merkur Lekarski ; 38(224): 93-9, 2015 Feb.
Article in Polish | MEDLINE | ID: mdl-25771518

ABSTRACT

UNLABELLED: The products of lipids oxidation: peroxides, hydroxides, aldehydes, ketones, esters, alcohols and others show harmful activity against human organism. Presence of the compounds in baby's and children's food creates potential health hazard. Many of them cause infant's and children's diarrhoea, also, negatively influence development of nervous system, show cytotoxic, mutagenic and cancerogenic activity (e.g. malonicdialdehyde, 4-hydroxynonenal and others). AIM: The aim of the work was to assess the level of lipids peroxidation in milk substitute preparations for initial stage baby feeding, before their end of shelf-life. MATERIALS AND METHODS: The level of lipids peroxidation measured as TBARS (thiobarbituric acid reactive substances) concentrations was determined in 6 available on the Polish market milk substitute infant formulas. The determinations was carried out before the end of the shelf-life after 1,2,3,6,9 and 12 months after purchase. The level of lipid peroxidation was also determined after 3-4 and 21 days post opening. RESULTS: TBARS content in the infants food ready to be eaten depended on the time of preparation storage. The highest level of lipids peroxidation was observed in all the studied food after 12 months of storage and after 21 days after opening of the hermetical wrapping. Various level of lipids peroxidation in milk substitutes for infant nutrition resulted from different amounts and quality of plant oils used in production (different content of mono- and polyunsaturated fatty acids, presence of lack of linoleic and α-linolenic acids).


Subject(s)
Food Analysis/methods , Infant Formula/chemistry , Thiobarbituric Acid Reactive Substances/analysis , Humans , Infant , Infant Food/analysis , Infant, Newborn , Lipid Peroxidation , Poland
5.
Pol Merkur Lekarski ; 39(233): 281-6, 2015 Nov.
Article in Polish | MEDLINE | ID: mdl-26637092

ABSTRACT

UNLABELLED: Superoxide oxidase (SOD) is a key antioxidant enzyme protecting cells against oxidative stress, which might induce cancerogenesis. In tumor cells SOD influences the level of the reactive oxygen species (ROS) allowing for survival and proliferation. High rate of cells proliferation in tumor leads to their temporary hypoxia due to lower rate of angiogenesis. Therefore during tumor development, cancer cells function in conditions of hypoxia or tissue normoxia. AIM: The aim of study was to evaluate of SOD isoenzymes (SOD1 and SOD2) expression level in cell lines of primary (SW 480) and metastatic (SW 620) colorectal cancer, cultured in hypoxia (1% oxygen), tissue normoxia (10% oxygen), and atmospheric normoxia (21% oxygen). MATERIALS AND METHODS: Cells were cultured in MEM medium in different oxygen concentrations (1%, 10%, 21%) in hypoxic chamber with oxygenation regulator. The number of living cells in lines SW 480 and 620 was determined by trypan blue method. Expression of SOD1 and SOD2 at the mRNA level was determined by RT-PCR and PCR. RESULTS: In both studied cell lines (SW 480 and SW 620), the number of living cells (viability) was increased in hypoxia and atmospheric normoxia. The expression level of SOD1 and SOD2 in studied cell lines was different. The lowest level of expression of both SOD isoenzymes was observed in hypoxia. In conditions of atmospheric normoxia the expression level of SOD1 in SW480 cell line was increased, and similar in SW620 cell line comparing to tissue normoxia. Whereas the SOD2 expression level in atmospheric normoxia conditions in both cell lines was significantly increased. Observed differences were statistically significant (p ≤ 0,05). CONCLUSIONS: The profile of expression of SOD1 and SOD2 in cell lines SW480 and SW620 indicates differentiated response of tumor cells depending on access to oxygen. Low level of SOD isoenzymes expression in SW480 and SW620 cells in hypoxia indicates decreased production of ROS. Differences of SOD isoenzymes expression level in tissue normoxia indicate their compensatory action, allowing to maintain the balance between O2- removal and H2O2production in studied tumor cells. In atmospheric normoxia conditions increased expression level of SOD1 and SOD2 observed in studied cell lines points to oxidative stress.


Subject(s)
Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Neoplasm Metastasis/pathology , Neoplasm Metastasis/physiopathology , Superoxide Dismutase/metabolism , Cell Hypoxia , Humans , Reactive Oxygen Species/metabolism , Superoxide Dismutase-1 , Tumor Cells, Cultured
6.
Pol Merkur Lekarski ; 36(216): 407-11, 2014 Jun.
Article in Polish | MEDLINE | ID: mdl-25095643

ABSTRACT

Calcium regulates majority of metabolic processes within human organism and its optimal intake decreases risk of metabolic illnesses conditioned by diet. Deficiency of calcium results in higher body max index, increase risk of insulin resistance, diabetes type 2 and osteoporosis. Diet delivering full calcium load diminished impendency of hypertension; calcium regulates tension of smooth muscles of blood vessels, limits neurotransmitters activity and also diminish hazardous activity of sodium chloride. Anticancerogenic activity of calcium results from formation insoluble bile acids and fat acids salts, and most of all, from inhibition of intestine mucosa cells hyper proliferation. Due to presence of vitamin D3, CLA, proteins and bioactive peptides emerging from them, milk is more efficient in prophylaxis of diet conditioned illnesses than calcium supplements. Efficiency of milk and dairy products in treatment of obesity, sclerosis and hypertension has been proved by DASH diet.


Subject(s)
Calcium, Dietary/administration & dosage , Calcium, Dietary/metabolism , Animals , Calcium, Dietary/analysis , Cholecalciferol/metabolism , Dairy Products , Humans , Hypertension/diet therapy , Hypertension/prevention & control , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Milk/chemistry , Milk/metabolism , Muscle, Smooth/blood supply , Muscle, Smooth/metabolism , Neoplasms/prevention & control , Obesity/diet therapy , Obesity/prevention & control , Synaptic Transmission/physiology
7.
J Recept Signal Transduct Res ; 33(5): 313-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23906352

ABSTRACT

Nonopioid Sigma1 receptor (Sig1R) influences numerous metabolism functions including regulation of ion channels, reaction on stress and response to growth signals. Due to this influence, Sigma1 receptor ligands show anti-proliferative and cytotoxic action on tumor cells. Additionally its increased level is observed in some types of tumors. Colorectal cancer is one of the most common cancers worldwide and its clinical development is well described. The aim of the study was evaluation of Sigma1 receptor mRNA expression level in human colorectal cancer and colorectal cancer liver metastases at different stages of tumor development. The mRNA was isolated from 30 patients: 18 with colorectal cancer (CRC) and 12 with colorectal cancer liver metastases (CRCLM). The cDNA of Sig1R gene was amplified by polymerase chain reaction using specific primers. The level of Sig1R mRNA expression was determined by measurement of optical density. Sig1R expression level was increased in CRC and CRCLM. The highest level of Sig1R mRNA was observed in UICC stage III. We also showed significant interactions of UICC stage and tumor localization with Sig1R expression level. There were no interactions between UICC stage and age of patients, although we observed significantly decreased level of Sig1R mRNA in older patients. Clinical advancement stage, localization of tumor and age of patients seems to be an important factors influencing Sigma1 receptor expression level. It is probably due to double nature of Sig1R action - in certain conditions it could act pro- or antiapoptotic. This action might depend on Sig1R activity resulting from its expression level.


Subject(s)
Colorectal Neoplasms/genetics , Liver Neoplasms/genetics , RNA, Messenger/genetics , Receptors, sigma/biosynthesis , Aged , Aged, 80 and over , Apoptosis/genetics , Colorectal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Receptors, sigma/genetics , Sigma-1 Receptor
8.
Pol Merkur Lekarski ; 35(210): 397-401, 2013 Dec.
Article in Polish | MEDLINE | ID: mdl-24490473

ABSTRACT

Critical theories regarding proteins of anima origin are still and still popularized, though they are ungrounded from scientific point of view. Predominance of soya proteins over the animal ones in relation to their influence on calcium metabolism, bone break risk or risk of osteoporosis morbidity has not been confirmed in any honest, reliable research experiment. Statement, that sulphur amino acids influence disadvantageously on calcium metabolism of human organism and bone status, is completely groundless, the more so as presence of sulphur amino acids in diet (animal proteins are their best source) is the condition of endogenic synthesis of glutathione, the key antioxidant of the organism, and taurine stimulating brain functioning. Deficiency of proteins in the diet produce weakness of intellectual effectiveness and immune response. There is no doubt that limitation of consumption of animal proteins of standard value is not good for health.


Subject(s)
Bone and Bones/metabolism , Calcium/metabolism , Dietary Proteins/metabolism , Animals , Diet, Vegetarian/adverse effects , Glutathione/biosynthesis , Humans , Osteoporosis/metabolism , Protein Deficiency/immunology , Protein Deficiency/metabolism
9.
Pol Merkur Lekarski ; 33(195): 168-72, 2012 Sep.
Article in Polish | MEDLINE | ID: mdl-23157137

ABSTRACT

Milk fat is characterized by extensive pro-health activity. Its unique components, such as: short chain saturated fatty acids, conjugated linoleic acid (CLA), vaccenic acid, ether lipids (alkiloglicerols and alkiloglicerophospholipids), 13-methyltetradecanic acid and bioactive components of antioxidative activity, are important in prophylaxis, and even in therapy of cancer diseases. Advantageous influence to maintain pro- and antioxidative balance of organism is revealed by the components of milk fat: conjugated linoleic acid, vitamins A and E, and coenzyme Q10. Moreover, vitamin D3, phospholipids, ether lipids, cholesterol and 13-methyltetradecanic acid also reveal antioxidative activity.


Subject(s)
Antioxidants/pharmacology , Dietary Fats/pharmacology , Milk , Neoplasms/prevention & control , Animals , Cholecalciferol/pharmacology , Humans , Linoleic Acid/pharmacology , Neoplasms/diet therapy , Phospholipids/pharmacology , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Vitamin A/pharmacology , Vitamin E/pharmacology
10.
Pol Merkur Lekarski ; 33(193): 38-42, 2012 Jul.
Article in Polish | MEDLINE | ID: mdl-22993909

ABSTRACT

Arteriosclerosis of blood vessels, the main cause of heart attack and stroke, is a disease of multifactor pathogenesis. Multiple experimental, clinical and epidemiologic studies indicate that free radicals and lipid oxidation products take part in aterogenesis process. Homocysteine possess also cytotoxic activity leading to degradation of elastine of internal membrane of blood vessels. Deficiency of vitamin folic acid, B12 and B6 cause homocysteine accumulation in human organism. Identifying the arteriosclerosis with oxidation of LDL-cholesterol results with faulty conclusions. Metabolism of cholesterol in human organism depends on content of n-6 and n-3 polyunsaturated fatty acids, phospholipids, fitosterols, food fiber, Lactobacillus and antioxidants in the diet. In aterogenesis antioxidant defficiency, especially long-lasting ones, are more important then amount of fat itself. Considering cholesterol intake with average food and its absorption amounting 25-30%, one can conclude that amount of cholesterol in intestine originates in 90% from liver synthesis, which is excreted with bile, and in more than ten percent--from food. This is why reduction of cholesterol intake with food only little improves blood lipid indexes.


Subject(s)
Arteriosclerosis/etiology , Arteriosclerosis/metabolism , Cholesterol, Dietary/adverse effects , Cholesterol, Dietary/metabolism , Homocysteine/metabolism , Cholesterol/biosynthesis , Humans , Lipids/blood , Liver/metabolism
11.
Pol Merkur Lekarski ; 32(187): 50-4, 2012 Jan.
Article in Polish | MEDLINE | ID: mdl-22400181

ABSTRACT

Flavonoids are plant components of the diet. Their daily intake is about 1 g. In Poland the main source of flavonoids is tea, apples and onions. These compounds are characterized by a variety of biological activities and pharmacological effects. Especially important for human health are their antioxidant properties. This paper presents the current state of knowledge on the role and importance of flavonoids in the prevention of the initiation and development of cardiovascular diseases. Epidemiological observations, clinical research, in vitro and in vivo experimental studies clearly show a protective effect of flavonoids on the cardiovascular system. Their beneficial effects on the cardiovascular system involve the inhibition of low density lipoprotein (LDL) oxidation, the reduction of blood vessels permeability, antiplatelet and anti-inflammatory activity, and hypotensive and direct vasodilator action. Biological potential of flavonoids (especially the antioxidant activity) indicates the possibility of their use in primary and secondary prevention of atherosclerosis and its clinical consequences (heart attack, stroke, and others) as a safe potential therapeutic agents.


Subject(s)
Antioxidants/therapeutic use , Cardiovascular Diseases/drug therapy , Flavonoids/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antihypertensive Agents/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/etiology , Atherosclerosis/prevention & control , Blood Vessels/metabolism , Cardiovascular Diseases/complications , Cardiovascular Diseases/metabolism , Humans , Lipoproteins, LDL/metabolism , Oxidation-Reduction , Vasodilator Agents/therapeutic use
12.
Pol Merkur Lekarski ; 33(198): 364-9, 2012 Dec.
Article in Polish | MEDLINE | ID: mdl-23437710

ABSTRACT

On the basis of previous in vitro, in vivo and epidemiological studies was found that flavonoids among their many biological and pharmacological properties have a great anticancer potential. High intake of foods rich in these compounds, mainly vegetables and fruits is associated with a low rate of cancer in humans. Flavonoids may act at different stages of carcinogenesis: initiation, promotion and progression. The complex mechanism of antitumor action include: antioxidant activity, carcinogens inactivation, antiproliferation, block of the cell cycle, induction of apoptosis and differentiation, inhibition of angiogenesis and elimination of drug resistance. With multidirectional action in carcinogenesis and targeting its action only on cancer cells, it is suggested that these compounds may give a new perspective of their use in prevention and therapy of cancer.


Subject(s)
Anticarcinogenic Agents/pharmacology , Flavonoids/pharmacology , Neoplasms/drug therapy , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Differentiation/drug effects , Humans , Neovascularization, Pathologic/drug therapy
13.
Exp Parasitol ; 129(2): 158-63, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21782814

ABSTRACT

Many helminths cause long-lasting infections, living for several years in mammalian hosts reflecting a well balanced coexistence between host and parasite. There are many possible explanations as to how they can survive for lengthy periods. One possibility is their antioxidant systems, which can serve as defence mechanisms against host-generated oxygen radicals. Therefore, the aim of this experimental study was to examine the antioxidant system in Hymenolepisdiminuta during short (1.5 months young tapeworms) and long (1.5 years old tapeworms) term infection in the rat small intestine. The strobilae of H. diminuta tapeworms (14 young and three old) were divided into three pieces: the anterior part, containing the genital primordiae in the immature segments; the medial part, containing the early uterus in the mature, hermaphroditic proglottids and the terminal part with the mature gravid uterus in the gravid segments. Supernatants of these fragments were used for determination of markers of oxidative stress: concentration of thiobarbiturate reactive substances (TBARS) and of reduced glutathione (GSH), and the activity of antioxidant enzymes: superoxide dismutase (SOD1 and SOD2), catalase (CAT), glutathione peroxidases (GSHPxs), glutathione transferase (GST) and glutathione reductase (GSHR). The results indicated changes in levels of oxidative stress markers and antioxidant enzyme activity in both the young and old forms of H. diminuta. Relatively high activity of SOD (particularly in the anterior part of young tapeworms) was observed, as was increased activity of total GSHPx and a relatively high concentration of GSH in all parts of the tapeworms. These are caused by exposure to increased amount of ROS, which are produced during the inflammatory state. Due to the high activity of antioxidant enzymes, the anterior section of young and old tapeworms is equipped with a very effective antioxidant system. Old organisms also effectively resist oxidative stress due to reduced levels of lipid peroxidation and the high activity of GST, all of which suggest good adaptation to the hostile environment in the host's intestine.


Subject(s)
Antioxidants/metabolism , Hymenolepiasis/metabolism , Hymenolepis diminuta/metabolism , Intestine, Small/parasitology , Animals , Biomarkers/analysis , Catalase/analysis , Glutathione/analysis , Glutathione Peroxidase/analysis , Glutathione Reductase/analysis , Hymenolepiasis/parasitology , Hymenolepis diminuta/enzymology , Lipid Peroxidation , Male , Malondialdehyde/analysis , Oxidative Stress , Rats , Rats, Inbred Lew , Superoxide Dismutase/analysis , Thiobarbituric Acid Reactive Substances/analysis , Time Factors
14.
Pol Merkur Lekarski ; 31(184): 239-43, 2011 Oct.
Article in Polish | MEDLINE | ID: mdl-22097183

ABSTRACT

Since long plant fats are considered by nutritionists, dieticians and doctors, as main source of essential unsaturated fatty acids) n-6 and n-3 in human diet. On the market there is plenty of oils that can be consumed directly or used to frying. Last four decades consumption of oils increased several times due to stimulated by advertisement popularization of their pro-health activity. Plant oils supply mostly multi unsaturated fatty acids n-6 excess of which disadvantageously influence human health. Determinations of changes of oxidative stability of plant fats (during processing and storage) proved that consumption of oxidation products of fatty acids and sterols may be a reason of various diseases. Both epidemiologic and clinic studies indicated that if plant fats (both oils except this from olives and margarines) have possessed pro-health properties, their several times increased consumption would liquidate the problem of arteriosclerosis and its clinical complications (heart attack, stroke). For the present, every second death in the industrial countries results from the cardiovascular disease. Morbidity of cancer is also increasing and of neurological and neurodegenerative diseases is growing up vigorously.


Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/metabolism , Plant Oils/administration & dosage , Plant Oils/metabolism , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Causality , Humans , Neoplasms/epidemiology , Neoplasms/prevention & control , Neurodegenerative Diseases/epidemiology , Neurodegenerative Diseases/prevention & control , Oxidation-Reduction
15.
Pol Merkur Lekarski ; 31(185): 318-22, 2011 Nov.
Article in Polish | MEDLINE | ID: mdl-22299537

ABSTRACT

Animal fats are generally considered as a source of saturated fatty acids and cholesterol, identified with arteriosclerosis and its clinical complications (cardiovascular diseases with heart attack, stroke, cerebral claudication). The real reason of arteriosclerosis are inflammation states of blood vessel endothelium caused by oxidative stress, hiperhomocysteinemia, hipertrigliceridemia, presence of artificial trans isomers and excess of eicosanoids originated from poliunsaturated fatty acids n-6. Present status of science proves that both saturated fatty acids and cholesterol present in animal food can not cause inflammation state. Moreover, animal fats are source of antioxidants active both in food and in human organism. Due to high oxidative stability animal fats do not make threat to human health. Milk fat, though high content of saturated fatty acids and cholesterol, possesses comprehensive pro-health activity--against arteriosclerosis and cancerogenesis.


Subject(s)
Atherosclerosis/etiology , Atherosclerosis/metabolism , Dietary Fats/adverse effects , Dietary Fats/metabolism , Animals , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Homeostasis/physiology , Humans
16.
Pol Merkur Lekarski ; 31(181): 24-30, 2011 Jul.
Article in Polish | MEDLINE | ID: mdl-21870705

ABSTRACT

UNLABELLED: Quantitative and semi-quantitative determination of gene expression by PCR plays an important role in studying of tumors initiation and progression mechanisms. Selection of appropriate reference gene is a critical factor influencing the results of gene expression analysis. One of the most commonly used reference genes in PCR is beta2-microglobuline (beta2-M). Recent studies showed however that expression of some common reference genes might be unstable, therefore it is necessary to verify again their usefulness. The aim of the study was to determine the level of beta2-M mRNA in normal and tumor tissues of gastrointestinal tract due to adequate selection of reference gene in gene expression studies. MATERIAL AND METHODS: Samples were taken from 253 patients operated on for gastrointestinal tract tumors: 22 with oral cavity cancer, 12 with benign and 50 with malignant liver tumors, 86 with colorectal cancer, and 83 with metachronous metastases to liver. Also 56 patients with liver cirrhosis were studied, which was treated as pre-tumor state. Together 309 patients were studied. RNA was isolated from tissues by Chomczynski method. The expression level of 12-M was determined by reverse transcriptase PCR (RT-PCR) and given in terms of optical density values. RESULTS: Expression of beta2-M was observed in all studied tissues. There were no differences between normal and tumor tissue. The level of expression of beta2-M was different due to type of studied tissue (oral cavity, liver, colon). CONCLUSIONS: The lack of significant differences in beta2-M expression level in normal and tumor tissues indicated that beta2-M can be used as reference gene in studies of gene expression in gastrointestinal tract tumors. On the other hand differences of beta2-M expression level in different types of tissues point to its tissue specificity and suggest application in PCR of more than one reference gene.


Subject(s)
Gastrointestinal Neoplasms/genetics , beta 2-Microglobulin/metabolism , Adult , Aged , Aged, 80 and over , Gene Expression Profiling/methods , Genetic Markers/genetics , Humans , Middle Aged , Polymerase Chain Reaction/methods , Reference Values
17.
Toxicol Appl Pharmacol ; 248(3): 210-6, 2010 Nov 01.
Article in English | MEDLINE | ID: mdl-20708635

ABSTRACT

This work investigated the effect of N-acetyl-L-cysteine (NAC) on disulfiram (DSF) induced oxidative stress in Chinese hamster fibroblast cells (V79). An increase in oxidative stress induced by DSF was observed up to a 200 µM concentration. It was evidenced by a statistically significant increase of both GSH(t) and GSSG levels, as well as elevated protein carbonyl (PC) content. There was no increase in lipid peroxidation (measured as TBARS). DSF increased CAT activity, but did not change SOD1 and SOD2 activities. Analysis of GSH related enzymes showed that DSF significantly increased GR activity, did not change Se-dependent GPx, but statistically significantly decreased non-Se-dependent GPx activity. DSF showed also pro-apoptotic activity. NAC alone did not produce any significant changes, besides an increase of GSH(t) level, in any of the variables measured. However, pre-treatment of cells with NAC ameliorated DSF-induced changes. NAC pre-treatment restored the viability of DSF-treated cells evaluated by Trypan blue exclusion assay and MTT test, GSSG level, and protein carbonyl content to the control values as well as it reduced pro-apoptotic activity of DSF. The increase of CAT and GR activity was not reversed. Activity of both GPx was significantly increased compared to their values after DSF treatment. In conclusion, oxidative properties are at least partially attributable to the cellular effects of disulfiram and mechanisms induced by NAC pre-treatment may lower or even abolish the observed effects. These observations illustrate the importance of the initial cellular redox state in terms of cell response to disulfiram exposure.


Subject(s)
Acetylcysteine/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Disulfiram/toxicity , Oxidative Stress/drug effects , Animals , Apoptosis/physiology , Cell Line , Cricetinae , Cricetulus , Disulfiram/antagonists & inhibitors , Dose-Response Relationship, Drug , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/physiology , Lipid Peroxidation/drug effects , Lipid Peroxidation/physiology , Oxidative Stress/physiology
18.
Postepy Hig Med Dosw (Online) ; 64: 38-49, 2010 Feb 12.
Article in Polish | MEDLINE | ID: mdl-20173219

ABSTRACT

Cadmium (Cd) is the main environmental pollutant. This metal presents a serious threat to the health of people and animals. The environmental risk can lead to the absorption of large quantities of cadmium and its toxic action on the organism. It adversely affects a number of organs in humans and animals, including the kidneys, liver, lungs, pancreas, and testis. The liver and kidneys, which are the primary organs involved in the elimination of this metal from the organism, are especially sensitive to its toxic effects. This paper presents the current state of knowledge related to the molecular mechanisms of the toxic action of cadmium in cells. Different mechanisms are discussed: the disruption of the cellular antioxidant system and decrease in thiol status, the generation of reactive oxygen species, inhibition of DNA repair and DNA methylation, the activation of cellular signals and protooncogenes, disruption of cell adhesion, cell damage leading to apoptosis, the promotion of cell proliferation, and the initiation of mutagenesis/carcinogenesis.


Subject(s)
Apoptosis/drug effects , Cadmium/toxicity , Carcinogens, Environmental/toxicity , Gene Expression Regulation/drug effects , Signal Transduction/drug effects , Environmental Pollutants , Humans , Oxidative Stress , Risk Factors
19.
Pol Merkur Lekarski ; 29(173): 309-14, 2010 Nov.
Article in Polish | MEDLINE | ID: mdl-21268915

ABSTRACT

UNLABELLED: Oxygen free radicals and their reactive derivatives participate in formation of chronic inflammation states, which facilitate development of gastrointestinal tract tumors. Oxidative stress is one of the main causes of damage to cell membranes in result of exacerbated lipid peroxidation process. End products of lipid peroxidation (aldehydes, organic peroxides) react with important biological macromolecules such as DNA and proteins, cause changes in cell membrane structure and properties leading to loss of its integrity. Intensification of the lipid peroxidation process is a factor which may also lead to a malfunction in the antioxidant barrier, which further weakens the defense of cells against oxygen free radicals and promotes the onset and development of cancer. The aim of the study was the determination of lipid peroxidation level in gastrointestinal tract tumors (stomach, liver, colon, and colorectal cancer to liver metastases). MATERIAL AND METHODS: Materials for studies were obtained from 150 patients with gastrointestinal tract tumors: 10 with stomach cancer, 30 with malignant and benign liver cancers, 60 with primary colorectal cancer, and 50 with metachronous colorectal cancer liver metastases. We also investigated 25 patients with liver cirrhosis, which was treated as a pre-cancerous condition. In total, 175 patients were examined. Tumor specimens, and normal adjacent tissues (6-7 cm from the edge of the tumor), which served as control tissue in studies, were collected from patients (with their consent) during surgery. Additionally, liver specimens were collected from patients with liver cirrhosis. Lipid peroxidation level was determined spectrophotometrically as a concentration of final lipid peroxidation products, which in reaction with tiobarbituric acid (TBA) form colour complex (thiobarbituric acid-reactive substances - TBARS). RESULTS: The study showed the highest concentration of TBARS in benign, and the lowest in malignant liver tumors. Other types of gastrointestinal tumors studied, were characterized by similar levels of lipid peroxidation. TBARS concentration in these tumors was approximately 2-fold higher than in malignant liver tumors and much lower than in benign tumors. In all cancers of the digestive tract with the exception of malignant liver tumors increased level of TBARS was found, comparing with control tissue. The concentration of TBARS in cirrhotic liver was lower than in control. The level of lipid peroxidation in liver cirrhosis and malignant liver tumors was similar. There were no significant differences in TBARS concentration in the tumors of particular sections of the intestine and normal colon. The highest concentration of TBARS was found in G1 grade of colorectal cancer. In subsequent grades of cells differentiation (G2 and G3) its concentration was lower. The highest level of lipid peroxidation, expressed as the concentration of TBARS was found in the I stage of colorectal cancer clinical advancement. The significantly lowest concentration of TBARS was shown for stage II (UICC). CONCLUSIONS: The level of lipid peroxidation in cancerous cells of gastrointestinal tract indicates increased oxidative stress. The changes of lipid peroxidation level--a marker of oxidative stress in gastrointestinal tumors appear to be closely associated with their development stages (liver cirrhosis/malignant liver cancer; colorectal cancer/colorectal cancer liver metastases) and are likely to create such conditions, in which cancerous cells may proliferate, undergo gradual dedifferentiation and malignancy, and generate metastases.


Subject(s)
Gastrointestinal Neoplasms/metabolism , Lipid Peroxidation , Liver Neoplasms/secondary , Adult , Aged , Female , Gastrointestinal Neoplasms/pathology , Humans , Liver Cirrhosis/metabolism , Liver Neoplasms/metabolism , Male , Middle Aged , Oxidative Stress
20.
Wiad Lek ; 63(3): 180-7, 2010.
Article in Polish | MEDLINE | ID: mdl-21125741

ABSTRACT

INTRODUCTION: Clinical and experimental studies indicate oxygen free radicals and their reactive derivatives participation in formation of chronic inflammation states, which facilitate gastrointestinal tract tumors development. During malignant changes formation in epithelium of gastrointestinal tract increased oxygen radicals generation initiates lipid peroxidation and DNA and proteins oxidation processes. Final lipid peroxidation products (saturated and unsaturated aldehydes) are highly reactive and characterized by greatly longer half life time than reactive oxygen species and capability to diffuse from places of their formation to distant cell areas. In cells they react with important biological macromolecules such as DNA and proteins causing their structural and functional damages. The effects of changes in cell membranes structure are increase in their permeability, depolarization, decrease of hydrophobicity and inhibition of enzymes, membrane channels and transporters. These changes lead to the loss of cell integrity. STUDY AIM: Determination of lipid peroxidation level in blood serum patients with gastrointestinal tract tumors. MATERIALS AND METHODS: Materials for studies were obtained from 170 patients with gastrointestinal tract tumors: 10 with stomach cancer, 20 with pancreatic cancer, 30 with primary liver cancer, 60 with primary colorectal cancer and 50 with metachronic colorectal cancer liver metastases. Blood was taken from patients 1 day before and 6 days after surgery. Control blood was obtained from 53 healthy blood donors. Lipid peroxidation level was determined spectrophotometrically as a concentration of final lipid peroxidation products, which in reaction with tiobarbituric acid (TBA) form colour complex (thiobarbituric acid-reactive substances, TBARS). RESULTS: Higher lipid peroxidation level was observed in pre- and postoperative blood sera patients with gastrointestinal tumors in comparison to serum from healthy blood donors. CONCLUSIONS: Increased lipid peroxidation level in peripheral blood of patients with gastrointestinal tract tumors is evidence of intensive oxidative stress and might indicate impairment of antioxidant defense mechanisms in organism.


Subject(s)
Gastrointestinal Neoplasms/blood , Lipid Peroxidation , Adult , Aged , Aged, 80 and over , Female , Humans , Liver Neoplasms/blood , Liver Neoplasms/secondary , Male , Middle Aged , Postoperative Period , Preoperative Period
SELECTION OF CITATIONS
SEARCH DETAIL