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Semecarpus anacardium L. nut extract administration induces the in vivo antioxidant defence system in aflatoxin B1 mediated hepatocellular carcinoma.

The antioxidant defence system which plays a critical role in carcinogenesis is severely altered in aflatoxin B1 induced hepatocellular carcinoma conditions. In order to assess the antitumour activity of Semecarpus anacardium nut extract, a flavonoid containing drug, non-enzymic antioxidant levels were analysed in control and experimental animals. Plasma was analysed for uric acid, vitamin E and vitamin C. Glutathione, total thiols, non-protein thiols, vitamin E, vitamin C and cytochrome P450 were estimated in liver and kidney homogenates. Depletion of all these antioxidants were recorded in cancer conditions. These deleterious effects are controlled by the administration of Semecarpus anacardium nut extract. Following drug administration, there was a marked increase in antioxidant levels and a dramatic elevation in cytochrome P450 content. It can be concluded that the observed anticancer property of Semecarpus anacardium nut extract may also be explained by its strong antioxidant capacity and capability to induce the in vivo antioxidant system.

Aflatoxin B1↗

Theoretical and literary evidence for the existence of the passive antitumor defence system.

It is well documented that despite global abnormalities of the immune system in AIDS and other immune deficiency diseases or in immunosuppressed patients the incidence of only a few kinds of tumour increases and even in the development of tumours in question the degree of immunosuppression seems not to be a critical factor. It results from this that the known immune system has no significant role in the mechanism that prevents the development of tumours. Consequently, the fact that tumours do not develop in the majority of the population during their lifetime, indicates the existence of other defence systems. We assumed that the defence is made by small substances of the circulatory system. Substantial evidence exists that the uptake of the majority of these substances is increased and unregulated by tumour cells and proportional to their availability. This feature of tumour cells may be fatal when the number of cells is still low and there are abundant substances in their environment because some substances may be toxic if their concentrations can reach high level in the cells. Thus, the arising cancer cells die in the majority of the population during their lifetime if the number of cells arisen is not too high, or the concentrations of the required substances are not too low. To our hypothesis, the above effects of the physiological mixture of the given molecules in the blood form the Passive Antitumor Defence System (PADS). This hypothesis is confirmed by our experiments and supported by epidemiological, clinical observations and other literary data.

Acquired Immunodeficiency Syndrome↗

Dietary vitamin-E modulates antioxidant defence system in giant freshwater prawn, Macrobrachium rosenbergii.

The objectives of the present study were to determine the effect of supplementary vitamin-E (200, 400 and 600 mg/kg feed) on lipid peroxidation (LPX) and antioxidant defence system in gills and hepatopancreas of the freshwater prawn, Macrobrachium rosenbergii. Results indicated that vitamin-E inhibited LPX in the hepatopancreas in a comparatively lower dose than gills. Superoxide dismutase (SOD) activity was decreased significantly in gills in response to all the three supplemented diet, but in hepatopancreas decrease was observed only in response to higher doses of vitamin-E (400 and 600 mg/kg feed). Catalase (CAT) activity was reduced significantly only in gills but not in hepatopancreas. While glutathione peroxidase (GPX) activity was significantly elevated in the hepatopancreas by vitamin-E, its activity remains unaltered in gills. On the contrary, glutathione reductase (GR) activity was decreased in gills but that of hepatopancreas was constant. Glutathione (GSH) content of both gills and hepatopancreas was substantially elevated in the vitamin-E supplemented prawns. Although the ascorbic acid (ASA) content of gills was unchanged by vitamin-E, its level elevated significantly in hepatopancreas. Thus the findings of the present investigation suggest that dietary vitamin-E is capable of reducing LPX level and can modulate antioxidant defence system in gills and hepatopancreas, nevertheless, the response is highly tissue specific. It is further observed that highest dose of vitamin-E (600 mg/kg feed) could not render much additional protection in both the tissues.

Animal Feed↗

The influence of hypomagnesemia on erythrocyte antioxidant enzyme defence system in mice.

The effect of magnesium deficiency on antioxidant defence system was studied in RBC of mice suffering from hypomagnesemia. The animals were kept for 8, 15 and 22 days on magnesium-deficient diet with consequent reduction of magnesium level in plasma by 38% at the first 8 days and by 64% after 22 days of experiment. The activities of the most important antioxidant enzymes, catalase, glutathione peroxidase, superoxide dismutase, glutathione reductase, glutahione S-transferase were assayed in hemolysates. The level of reduced glutathione in erythrocytes was measured as well. Apart from catalase, the activities of antioxidant enzymes were decreasing. The activity of superoxide dismutase decreased gradually during the experiment and on the 15th and 22nd day of experiment was significantly (P < 0, 05) lowered by 30 and 32% respectively. The catalase activity was increased on each point of the experiment with the peak value up to 149% on 15th day, and by 32% on 22nd day. Glutathione peroxidase activity was insignificantly reduced. The reduction of Glutatione reductase and Glutathione S-transferase activities by 24 and 21%, respectively, were observed after 8 days of the experiment with a further downward tendency. The reduced glutathione was significantly depleted after 8 days by 33% and was kept on that level in the course of the study. These findings support previous reports on the hypomagnesemia--induced alteration in endogenous enzyme antioxidant defences and glutathione redox cycle of mice.

Animals↗

The effects of melatonin and the antioxidant defence system on apoptosis regulator proteins (Bax and Bcl-2) in experimentally induced varicocele.

Our aim was to examine the effects of melatonin on the testicular tissue of adult rats with experimentally-induced left varicocele, and to determine the relationship between melatonin and apoptosis regular proteins in the anti-oxidant defence system. Forty adult male Wistar rats were divided equally into four groups. A sham operation was performed on the rats in group I, and experimental left varicocele was created in groups II, III and IV. Melatonin was administered intraperitoneally at doses of 5 mg/kg and 10 mg/kg to rats in groups III and IV, respectively. An immunohistochemical analysis of the left testicular tissue was performed to evaluate the expression of Bax and Bcl-2, while tissue malondialdehyde (MDA) and antioxidant enzyme activities were assessed in homogenates to determine the role of the oxygen defence system. The immunohistochemical analysis revealed an increased ratio of pro-apoptotic protein Bax in groups II and III, whereas no significant activity was observed in the sham operated rats ( P<0.05). Similarly, the tissue MDA level increased and a significantly decreased level of antioxidant enzymes was observed in these groups ( P<0.05). Although rats in group IV showed a slightly increased ratio of the pro-apoptotic marker Bax, there was no significant difference between groups I and IV. Similarly, group IV showed decreased levels of MDA and increased levels of anti-oxidant enzyme activity with decreased Bax expression. The close relationship between pro-apoptotic/anti-apoptotic markers, reactive oxygen species and antioxidant agents provided a useful in vivo model for studying the pathophysiology of varicocele and evaluating the role of antioxidants in the prevention testicular damage.

Animals↗

Bacteriophage defence systems in lactic acid bacteria.

The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection.

Animals↗

Seasonal variations in the antioxidant defence systems and lipid peroxidation of the digestive gland of mussels.

1. The seasonal variations in the level of antioxidant compounds (glutathione (GSH), vitamin E, carotenoids) and in the activity of antioxidant enzymes, superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), GSH-peroxidase (EC 1.11.1.9) in the digestive gland of mussels (Mytilus sp.) were evaluated. The lipid peroxidation process was also measured by determining the tissue concentration of malondialdehyde (MDA). 2. The physiological fluctuations of the antioxidant defence systems were inversely related to the accumulation of lipid peroxidation products (MDA) in the tissue. The observed seasonal variations are presumably related to the changing metabolic status of the animals, itself dependent on such factors as gonad ripening and food availability. 3. In particular, the obtained data indicate that a reduction of the antioxidant defence systems, occurring during winter, could be directly responsible for an enhanced susceptibility of mussels tissues to oxidative stress, as indicated by the high MDA concentration observed in this period.

Animals↗

A newly discovered oxidant defence system and its involvement in the development of Aurelia aurita (Scyphozoa, Cnidaria): reactive oxygen species and elemental iodine control medusa formation.

In Aurelia aurita, applied iodine induces medusa formation (strobilation). This process also occurs when the temperature is lowered. This was found to increase oxidative stress resulting in an increased production of iodine from iodide. One polyp produces several medusae (initially termed ephyrae) starting at the polyp's oral end. The spreading of strobilation down the body column is controlled by a feedback loop: ephyra anlagen decrease the tyrosine content in adjacent polyp tissue by producing melanin from tyrosine. Endogenous tyrosine is able to remove iodine by forming iodiferous tyrosine compounds. The reduced level of tyrosine causes the ephyra-polyp-border to move towards the basal end of the former polyp. We argue that an oxidant defence system may exist which makes use of iodide and tyrosine. Like other marine invertebrates, polyps of Aurelia contain iodide ions. Inevitably produced peroxides oxidise iodide into iodine. The danger to be harmed by iodine is strongly decreased by endogenous tyrosine which reacts with iodine to form iodiferous tyrosine compounds including thyroxin. Both substances together, iodide and tyrosine, form an efficient oxidant defence system which shields the tissue against damage by reactive oxygen species. In the course of evolution (from a species at the basis of the animal kingdom like Aurelia to a highly evolved species like man) the waste product thyroxin (indicating a high metabolic rate) has developed into a hormone which controls the metabolic rate.

Animals↗

Alcohol-induced congestive cardiomyopathy in adult turkeys: effects on myocardial antioxidant defence systems.

The effects of chronic intake of dietary alcohol upon left ventricular function, activities of myocardial antioxidant enzymes, reduced glutathione (GSH) content and lipoperoxidation (measured as the formation of diene conjugates and lipid-soluble fluorescence) were studied in adult domestic Nicholas turkeys. The non-invasive evaluation of left ventricular function by echocardiography revealed an impaired contractile function (the calculated fractional shortening values were 31.1 +/- 4.1% in the alcoholic group and 38.8 +/- 4.4% in the controls) and dilatation of the heart in the alcoholic birds. The changes in the non-invasive parameters of the left ventricle indicate that the adult Nicholas turkey developed congestive cardiomyopathy secondary to the ingestion of ethanol. In the hearts of normal adult turkeys, high GSH content (2.39 +/- 0.25 mumol/g wet weight) and superoxide dismutase activity were found, as compared to other animals, indicating the relatively higher development of antioxidant defence systems. Compared to the controls, significant increases were noted for all the antioxidant enzymes investigated (superoxide dismutase, catalase and glutathione peroxidase) and a moderately significant decrease in the GSH content was found in the left ventricle of alcoholic birds. The changes in GSH concentration and antioxidant enzyme activities might indirectly indicate some involvement of free radicals in the pathogenesis of ethanol-induced myocardial lesion. However, the levels of in vivo lipoperoxidation in the alcoholic birds did not significantly vary from those of control turkeys. Based on these findings, it appears that the reactive oxygen radicals may play a less important role in the pathogenesis of alcohol-induced cardiomyopathy in turkeys--probably due to the higher development of myocardial antioxidant defence systems.

Alcoholism↗

Viewing AIDS from a glycobiological perspective: potential linkages to the human fetoembryonic defence system hypothesis.

The primary molecular changes that lead to development of acquired immunodeficiency syndrome (AIDS) are very poorly understood, as are the mechanisms underlying the protection of the developing human from the maternal immune response. Recent data that the human immunodeficiency virus (HIV) may be using the glycosylation system of the T lymphocytes to acquire glycans for its glycoproteins that enable it to disrupt carbohydrate dependent immune cell interactions or induce aberrant immune reactions. Consistent with this hypothesis, gp120 from HIV infected human H9 lymphoblastoid cells expresses biantennary N-linked glycans with a bisecting GlcNAc sequence on 11% of their total oligosaccharides. This specific carbohydrate sequence has recently been shown to protect K562 erythroleukemic cells from natural killer (NK) cell responses when presented on the cell surface. We have recently demonstrated that bisecting biantennary type N-linked glycans are also expressed on the human zona pellucida (ZP); previous lectin binding studies indicate that is also expressed on human spermatozoa. Thus both the human gametes and HIV produced by H9 cells carry this same protective carbohydrate epitope on their outer surfaces. Human alpha-fetoprotein expressed in the developing human also carries the bisecting GlcNAc sequence, indicating that it may be suppressing the emerging fetal immune response by using its carbohydrate sequence as a functional group. We have suggested that the developing human and the gametes are also protected by soluble immunosuppressive glycoproteins found in the amniotic fluid and seminal plasma known as glycodelin-A (GdA) and glycodelin-S (GdS) respectively. Structural analysis of their N-linked oligosaccharides combined with other functional studies suggest that GdA and GdS employ their very unusual carbohydrate sequences as functional groups that enable them to manifest their immunosuppressive activities. GdA and GdS are significant components of our recently proposed model for the protection of the developing human and gametes designated the human fetoembryonic defence system hypothesis. A striking relationship now emerging is that the same unusual carbohydrate sequences associated with these immunosuppressive glycodelins are also specifically expressed on intravascular helminthic parasites, Helicobacter pylori, human tumour cells, and HIV infected T lymphocytes. The information presented in this review suggests that two new corollaries should be added to our recently proposed defence system hypothesis: (i) mimicry or acquisition of glycans that are used in this protective system by pathogens or tumour cells may enable them to either subvert or misdirect the human immune response, thereby greatly increasing their pathogenicity; and (ii) expression of glycoproteins used in this system by normal cells and tissues outside the reproductive system may protect them from immune responses, especially in those cases where major histocompatibility recognition is either absent or minimal. A better understanding of this hypothesis and its corollaries may enable us to address the molecular mechanisms underlying not only AIDS but also a host of other very serious pathological conditions in the human.

Acquired Immunodeficiency Syndrome↗

Escape-related behaviours in an unstable, elevated and exposed environment. II. Long-term sensitization after repetitive electrical stimulation of the rodent midbrain defence system.

The behavioural indices of anxiety/fear/panic range from freezing/inhibition of ongoing behaviour to active defence strategies i.e. fight/flight, depending on the proximity or intensity of the aversive stimulus. However, evidence suggests that when the initial stressor is sufficiently intense, the neural defence circuitry may undergo a long-term increase in sensitivity. Such sensitization has been evoked to explain the chronically hyper-aroused fight/flight state of patients suffering from extreme anxiety states. The purpose of this study was to establish whether direct activation of the rodent midbrain defence system could result in a similar long-term alteration of the animal's responses to subsequent stressful events. This was achieved by studying the behaviour of animals in a threatening environment after repetitive electrical stimulation of the superior colliculus. Animals were then placed on an unstable, elevated and exposed plus maze and their behaviour recorded. Testing was carried out regularly over 3 months. Stimulated animals reliably exhibited significantly increased levels of behaviours designed to escape the aversive conditions of the unstable plus maze. These included visual scanning, end-reaching, preparing to jump, and jumping off the apparatus. Unstimulated control animals, on the other hand, exhibited decreased levels of these behaviours post-stimulation. In contrast, the experimental animals' performance on standard anxiety tests did not differ from controls. These results demonstrate that repetitive tactile stimulation can produce a long-term change in reactions to threat, and is proposed as a functional model of extreme anxiety.

Animals↗

Aluminium phosphide exposure: implications on rat brain lipid peroxidation and antioxidant defence system.

We investigated the effect of aluminium phosphide exposure (10 mg/kg body weight) on lipid peroxidation and antioxidant defence system in different regions of rat brain. A significant increase in lipid peroxidation in cerebrum, cerebellum and brain stem was observed in aluminium phosphide-exposed rats, which was accompanied by a marked decrease in the activities of antioxidant enzyme, superoxide dismutase and catalase. A decline in the activity of glutathione reductase was also observed, however, no change was seen in the activity of glutathione peroxidase following aluminium phosphide administration. Decreased levels of non-protein thiols and total sulfhydryl groups were also observed after aluminium phosphide treatment. It seems evident that aluminium phosphide exposure significantly enhanced neuronal lipoperoxidative damage with concomitant alterations in the antioxidant defence status thus having serious bearing on the functional and structural status of the central nervous system.

Administration, Oral↗

[Recent advances in research on disease resistance genes in defence system of plant].

This review comments on recent advances in research of disease resistance genes(R Genes) in defence system of plants. The R genes cloned up to date are summarized and classified roughly into four classes listed in the Table 1. The location and the function of the R proteins, i.e., the expressed products of different R genes in the cells are reviewed. In addition, the polymorphism of coding region of R genes, the different fashions of R gene arrangement on the chromosomes, and the evolution and origin of R genes are discussed.

English Abstract↗

Failure of fibronectin as an opsonin in the host defence system: a case of competitive self inhibition?

In the course of various clinical conditions, consumption of opsonic fibronectin is thought to impair the function of the reticuloendothelial (RE) host defence system. Despite evidence to support its central role in host defence, measurements of circulating fibronectin levels appear to have limited diagnostic or prognostic value. It seems that the problem may be more complex than a simple depletion of fibronectin. It is proposed that the structure of fibronectin can allow a condition of opsonic dysfunction to arise in certain patients, irrespective of the concentration of immunoreactive fibronectin. Fibronectin fragments bound to the target particles (fibrin aggregates, tissue debris, microorganisms) would prevent the binding of fibronectin and so inhibit phagocytosis by cells of the RE system.

Bacterial Infections↗

The effect of ascorbic acid supplementation on some parameters of the human immunological defence system.

We have investigated the effect of ascorbic acid (vitamin C) supplementation on some parameters of the human immune defence system in a group of 25 healthy, male university students. The subjects ingested 1 g ascorbic acid per day for a period of 75 days. Serum levels of IgA, IgG, IgM, C-3 complement component, cortisol and transcortin were measured before and after the ascorbic acid course. Corresponding measurements were performed on a control group of 20 healthy, male university students receiving no extra-dietary vitamin C. Our results showed that ascorbic acid supplementation caused a statistically significant increase in the serum levels of IgA, IgM and C-3 complement. Our study does not permit of conclusions regarding the mechanisms of action of ascorbic acid.

Adolescent↗

Effects of open heart surgery on oral mucous host defence systems.

BACKGROUND: The immune response is affected by anaesthesia and surgery. This study was carried out on the effects of open heart surgery on the oral mucous host defence system, which is part of the common mucosal immune system. METHODS: Amylase, nonimmunological (lysozyme, myeloperoxidase, hypothiocyanite and thiocyanate) and immunological (IgA, IgG, and IgM) mucous host defence factors as well as oral bacterial flora were determined in the saliva of 18 patients undergoing open heart surgery preoperatively and on the 2nd, 3rd, and 7th postoperative days. To assess the specificity of the changes, the salivary flow rate and total protein content were also determined. RESULTS: Stimulated salivary flow decreased from 1.8 (1.3-2.2) ml/min (median; 25th and 75th quartiles) to 0.4 (0.3-0.5) ml/min by the 2nd postoperative day and to 0.4 (0.2-1.0) ml/min by the 3rd postoperative day (P < 0.001). Amylase, lysozyme, myeloperoxidase, total salivary peroxidase and thiocyanate levels increased, whereas hypothiocyanite levels decreased postoperatively (p < 0.01-0.001). Their total secretion rate, however, was reduced (P < 0.05-0.001) owing to the lowered salivary flow rate. IgG and IgM concentrations were raised on the 2nd, 3rd and 7th postoperative days (P < 0.05-0.001), and IgA concentrations on the 2nd postoperative day (P < 0.05). The total secretion of IgG and IgM as well as their salivary concentrations in relation to total protein concentrations also increased. The number of salivary anaerobically growing bacteria decreased postoperatively (P < 0.01), but the number of salivary streptococci remained unaffected. CONCLUSIONS: Open heart surgery decreases the salivary secretion of nonimmunological host defence factors and increases the salivary secretion of IgA, IgG and IgM.

Adult↗

The anti-oxidative defence system in the isolated rat uterus during spontaneous rhythmic activity.

Possible interactions between nitric oxide donors, reactive oxygen species and anti-oxidative defence enzymes led us to determine the activities of anti-oxidative defence enzymes in isolated uterine smooth muscle before and after spontaneous rhythmic activity ex vivo. For our experiments we used isolated uteri from female Wistar rats. Our results showed an increase in total superoxide dismutase (SOD) and Mn SOD activities in uterine smooth muscle after spontaneous contractions when compared with nonexercised uterine smooth muscle. The activity of catalase (CAT) and glutathione preoxidase (GSH-Px) were also increased. No statistically significant changes in the activities of glutathione reductase (GR) and CuZn SOD were found. It is known that an organism's anti-oxidative defence system (guarding against excessive reactive oxygen species generation) requires balanced increments in its individual anti-oxidative enzyme activities rather than increases in the activity of only some enzymes without increases in others. Thus, we may conclude that some adaptive responses are found in exercised uterine smooth muscle but are not complete. Therefore, our results indicate that changes in anti-oxidative enzyme activities may influence the results of the examination of substances ex vivo.

Animals↗

Interactions between genes involved in the antioxidant defence system and breast cancer risk.

The aim of the study is to examine the association between multilocus genotypes across 10 genes encoding proteins in the antioxidant defence system and breast cancer. The 10 genes are SOD1, SOD2, GPX1, GPX4, GSR, CAT, TXN, TXN2, TXNRD1 and TXNRD2. In all, 2271 cases and 2280 controls were used to examine gene-gene interactions between 52 single nucleotide polymorphisms (SNPs) that are hypothesised to tag all common variants in the 10 genes. The statistical analysis is based on three methods: unconditional logistic regression, multifactor dimensionality reduction and hierarchical cluster analysis. We examined all two- and three-way combinations with unconditional logistic regression and multifactor dimensionality reduction, and used a global approach with all SNPs in the hierarchical cluster analysis. Single-locus studies of an association of genetic variants in the antioxidant defence genes and breast cancer have been contradictory and inconclusive. It is the first time, to our knowledge, the association between multilocus genotypes across genes coding for antioxidant defence enzymes and breast cancer is investigated. We found no evidence of an association with breast cancer with our multilocus approach. The search for two-way interactions gave experiment-wise significance levels of P=0.24 (TXN [t2715c] and TXNRD2 [g23524a]) and P=0.58 (GSR [c39396t] and TXNRD2 [a442g]), for the unconditional logistic regression and multifactor dimensionality reduction, respectively. The experiment-wise significance levels for the three-way interactions were P=0.94 (GPX4 [t2572c], TXN [t2715c] and TXNRD2 [g23524a]) and P=0.29 (GSR [c39396t], TXN [t2715c] and TXNRD2 [a442g]) for the unconditional logistic regression and multifactor dimensionality reduction, respectively. In the hierarchical cluster analysis neither the average across four rounds with replacement of missing values at random (P=0.12) nor a fifth round with more balanced proportion of missing values between cases and controls (P=0.17) was significant.

Adult↗