The anticarcinogenic potential of milk fat.

INTRODUCTION AND OBJECTIVE: The anticarcinogenic potential of milk fat can be attributed to its antioxidant, anti-inflammatory, immunostimulatory properties as well as the presence of compounds with antimutagenic effects. In view of the high incidence of cancer the aim of this article was to review the literature concerning the biological activity of milk fat components. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Conjugated linoleic acid (CLA), coenzyme Q10, phospholipids, ß-carotene, and vitamins A, D and E play an important role in the pro-oxidant/antioxidant homeostasis. The anti-inflammatory properties of milk fat can be attributed to the presence of phospholipids and short- and medium-chain saturated fatty acids. Conjugated linoleic acid has immunostimulatory properties, and it influences the proliferation and activity of lymphocytes and macrophages. Saturated (C10 and C12) and unsaturated (C18) fatty acids, as well as sphingolipids, exert bactericidal effects in the gastrointestinal tract. Vaccenic acid, CLA and sphingomyelin possess antimutagenic and anticarcinogenic properties. Butyric acid promotes the apoptosis of cancer cells in the liver, and delivers positive effects in the treatment of breast and colorectal cancer. Alkylglycerols activate macrophages, stimulate phagocytosis and, most importantly, the apoptosis of cancer cells. CONCLUSIONS: The health benefits of milk fat are not fully exploited due to its low consumption. Therefore, only some epidemiological studies have shown a negative correlation between the consumption of high-fat dairy products and the incidence of cancer. More research is needed involving human clinical trials to allow a better understanding of the anticancer biochemistry related with milk fat compounds.

Effect of different concentrations of oxygen on expression of sigma 1 receptor and superoxide dismutases in human colon adenocarcinoma cell lines.

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.

[The role of flavonoids in the modulation of inflammation]. / Rola flawonoidów w modulacji stanu zapalnego.

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.

[The level of superoxide dismutase expression in primary and metastatic colorectal cancer cells in hypoxia and tissue normoxia]. / Liczba zebów oraz profil hormonalny u kobiet po menopauzie z osteoporoza, osteopenia oraz prawidlowa gestoscia tkanki kostnej - badania wstepne.

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.

[Milk fat - the only existing for any reason]. / Tluszcz mlekowy - unikalny pod kazdym wzgledem.

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.

[The level of lipid peroxidation in milk replacer formulas for initial feeding of infants]. / Poziom peroksydacji lipidów w mlekozastepczych preparatach do zywienia poczatkowego niemowlat.

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).

Multiple protective functions of sigma1 receptor.

The Sigma Receptor 1 (sig-1R) is a protein present in numerous normal tissues, such as brain, retina, lens, liver, lung, heart, but also in many tumor lines. Its amino acid sequence is homologous to fungal C-8,7 sterol isomerase, but it has no known homology with mammalian proteins and does not possess sterol isomerase activity. It is localized in plasma and ER membranes, and its exact function is not clarified as of yet. Last reports point to its participation in regulation of ionic channels activity, particularly calcium channels. Application of numerous synthetic ligands of sigma1 receptor provided means to study its protective effects and metabolic functions in different tissues. This review describes influence of sigma1 receptor on various aspects of cellular metabolism, such as calcium signalling, mitochondrial functions, oxidative stress, survival and apoptotic pathways, and tumor cells proliferation.

[Calcium--essential for everybody]. / Wapn--niezbedny dla kazdego.

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.

Altered expression level of Sigma1 receptor gene in human colorectal cancer.

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.

Modulation of antioxidant defense system by the dithiocarbamate fungicides Maneb and Zineb in Chinese hamster V79 cells and the role of N-acetyl-L-cysteine.

Oxidative stress is one of the major factors leading to Maneb- and Zineb-induced disorders. The aim of this in vitro study was to examine (i) the potency of Maneb and Zineb to induce changes in antioxidant enzyme activities in Chinese hamster fibroblasts V79 cells and (ii) the role of N-acetyl-L-cysteine (NAC) in the preventing their action. Maneb increased mitochondrial superoxide dismutase (SOD2) activity but failed to affect the activity of cytoplasmic superoxide dismutase (SOD1), whereas Zineb did not change the activity of any of superoxide dismutases. The activity of catalase (CAT) was reduced only by Zineb. The activity of both glutathione peroxidases (non-Se-GPx, Se-GPx) and glutathione reductase (GR) was decreased after exposure to these agents. After NAC pre-treatment Maneb increased the activity of GR, whereas the activity of non-Se-GPx was decreased as compared to that in NAC-treated cells. On the other hand, the activity of both SODs and CAT was decreased. Zineb decreased the activity of both GPxs and SOD2 with a concomitant increase in CAT activity comparing to NAC-treated cells. The results obtained thus suggest that Zineb acts by another mechanism, than Maneb does, and that one of the mechanisms of NAC protection against Maneb or Zineb-induced effects in V79 cells is its impact on enzymatic defense. Activity of GR, SOD2, and GPxs are the most affected enzymes.

[Controversies around diet proteins]. / Kontrowersje wokól bialek diety.

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.

[Milk fat in prophylaxis of cancer diseases]. / Tluszcz mlekowy w profllaktyce chorób nowotworowych.

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.

[The food cholesterol controversy]. / Kontrowersje wokól cholesterolu pokarmowego.

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.

[Flavonoids in the prevention and treatment of cardiovascular diseases]. / Flawonoidy w prewencji i leczeniu chorób ukladu sercowo-naczyniowego.

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.

[Anticancer activity of flavonoids]. / Przeciwnowotworowe dzialanie flawonoidów.

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.

[Spuriously healthy plant fats]. / Rzekomo zdrowe tluszcze roslinne.

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.

[Evaluation of beta2-microglobuline expression level in gastrointestinal tract tumors due to usefulness as a reference gene in PCR method]. / Ocena poziomu ekspresji beta2-mikroglobuliny w nowotworach przewodu pokarmowego pod wzgledem przydatnosci jako genu referencyjnego w metodzie PCR.

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.

Hymenolepis diminuta: experimental studies on the antioxidant system with short and long term infection periods in the rats.

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.

[Spuriously unhealthy animal fats]. / Rzekomo niezdrowe tluszcze zwierzece.

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.