Antioxidant Ones Research Articles

Oxidative Stress Evaluation in Patients Treated with Orthodontic Self-ligating Multibracket Appliances: An in Vivo Case-Control Study.

Objective:Oxidative stress is a pathologic event induced by a prevalence of oxidant agents on the antioxidant ones, with a consequent alteration of oxide-reducing balance.Introduction:Freeradicals produce damages both in cellular and extra-cellular components; phospholipid membranes, proteins, mitochondrial and nuclear DNA, are the target of the oxidative stress, that can finally cause cellular death due to apoptosis.Materials & Methods:Orthodontic appliances such as brackets, wires, resins and soldering have some components that can be considered as potential allergen, carcinogenic, cytotoxic and gene mutation factors. The primary aim of this research is to evaluate oxidative stress in the saliva of patients treated with multibracket self-ligating vestibular orthodontic appliances; the secondary purpose is to investigate the influence of orthodontic multibracket therapy on oral hygiene and the consequent effect on oxidative stress. Salivary specimens has been collected in a sample of 23 patients were enrolled (12 Female, 11 Male) between 12 and 16 years of age (mean age 14.2). For each patient has been collected a salivary specimen at the following time points; before orthodontic bonding (T1), five weeks (T2) and ten weeks (T3) after orthodontic appliance bonding.Results:Samples has been analysed with a photometer due to SAT Test (Salivary Antioxidant Test). Data obtained show a mean of 2971 mEq/l of anti-oxidant agents before orthodontic treatment, and after five weeks from the bonding the mean was decreased to 2909 mEq/l, instead at ten weeks was increased to 3332 mEq/l. Repeated measures ANOVA did not reveal statistically significant differences between the time points (P = 0.1697). The study did not reveal any correlation between the level of dental hygiene and that of oxidative stress (Pearson Correlation Coefficient R = 0).Conclusion:Orthodontic treatment with multibrackets vestibular metallic appliance seems to be not able to affect oxidative stress during the first ten weeks of therapy.

Loliolide - the most ubiquitous lactone

The searching for biologically active compounds produced by living organisms led to the discovery of a number of compounds with more or less complicated structure. One of the simplest molecules are monoterpenoid lactones and loliolide is the most common among them. Loliolide was found in animals (insects) and plants (flowers, shrubs, trees) both terrestrial and marine, such as algae and corals. Many years of research on plants used in traditional folk medicine of different countries have led to the conclusion that this compound has a variety of biological properties such as anti-cancer, antibacterial, antifungal and antioxidant ones. Moreover, plants containing loliolide are used in alternative medicine in treatment of diabetes and depression. It is extremely interesting that this lactone also affects the behavior of ants as well as the development of certain plants (allelopathic activity). However, sometimes there are side effects as in the case of structural analogues of loliolide contributing to extinction of tropical coral.

The synthesis and physicochemical properties of 2-(5-methoxyphenyl-1H-1,2,4-triazole-3-ylthio) acetonitriles and their iminoethers

With the purpose of further search of biologically active substances among 5-(2-, 3-, 4-methoxyphenyl, 3,4,5- trimethoxyphenyl)-3-thio-1,2,4-triazoles and their derivatives 10 new compounds have been obtained. Acetonitrilothio- 1,2,4-triazoles have been synthesized by alkylation of 5-(2-, 3-, 4-methoxyphenyl and 3,4,5-trimethoxyphenyl)- 3-thio-1,2,4-triazoles with halogenonitriles; the primary computer pharmacological screening has shown that the class of compounds mentioned can show such types of the pharmacological activity as antitumor, antiinflammatory and antioxidant ones. Alkylation of 5-R-1,2,4-triazole-3-thiols has been carried out in the medium of anhydrous alcohol or aprotic solvents. It has been found that replacement of the alcoholic solvent by the aprotic one increases the quantitative yield of 5-R-1,2,4-triazol-3-thioacetonitrile; in aprotic solvents the presence of impurities of alkaline hydrolysis products is not practically observed. Iminoethers of 2-(5-(2-, 3-, 4-methoxyphenyl and 3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-ylthio)acetatic acids have been synthesized by saturation of 2-(5-(2-, 3-, 4-methoxyphenyl and 3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-3-ylthio)acetonitriles with the flow of dry in the alcoholic medium when constant cooling the reaction mixture to –5oC. It has been found by the method of HPLC/DAD-MS that the qualitative yield of the target product depends on the maintenance of the temperature mode of the reaction mixture. The structure and individuality of the molecules of the substances synthesized have been proven by the method of 1H NMR-spectroscopy and HPLC/DAD-MS.

Capsaicin triggers immunogenic PEL cell death, stimulates DCs and reverts PEL-induced immune suppression.

Capsaicin, the pungent alkaloid of red pepper has been extensively studied for its many properties, especially the anti-inflammatory and anti-oxidant ones. It binds to vanilloid receptor 1, although it has been reported to be able to mediate some effects independently of its receptor. Another important property of Capsaicin is the anticancer activity against highly malignant tumors, alone or in combination with other chemotherapeutic agents. In this study, we found that Capsaicin induced an apoptotic cell death in PEL cells correlated with the inhibition of STAT3. STAT3 pathway, constitutively activated in PEL cells, is essential for their survival. By STAT3 de-phosphorylation, Capsaicin reduced the Mcl-1 expression level and this could represent one of the underlying mechanisms leading to the Capsaicin-mediated cell death and autophagy induction. Next, by pharmacological or genetic inhibition, we found that autophagy played a pro-survival role, suggesting that its inhibition could be exploited to increase the Capsaicin cytotoxic effect against PEL cells. Finally, we show that Capsaicin induced DAMP exposure, as for an immunogenic cell death, directly promoted DC activation and, more importantly, that it counteracted the immune-suppression, in terms of DC differentiation, mediated by the PEL released factors.

Фенотипические особенности экспрессии фактора, индуцированного гипоксией, и редокс-статус клеток неокортекса крыс на разных стадиях адаптации к гипоксии

Hypoxic preconditioning induces two-phase increase of HIF-1alpha expression in the neocortex of low-resistance rats. The first, brief phase appears after each hypoxic episode and rapidly disappears in normoxic conditions. The second increase in of HIF-1alpha expression occurs in 24 hours after the hypoxic episode. The phase-nature of HIF-1alpha expression corresponds to the dynamics of urgent and long-term resistance in low-resistance rats, which suggests the HIF-1alpha involvement in mechanisms of urgent and long-term adaptation. It was found that in the mode of preconditioning, hypoxic treatments mobilized the anti-oxidant system (activated Cu, Zn-SOD) and had no effect on the intensity of lipid peroxidation processes in neocortex (INH, 10% O2) or even decreased the content of lipid peroxidation products and oxidized glutathione in neocortical cells in the early post-hypoxic period (HBH-5000, 10.5% O2). Thus, ROS do not play a key role in the induction of HIF-1alpha expression and fast-response/long-term adaptation to O2 deficiency in hypoxia-sensitive animals. In high-resistance rats, hypoxia preconditioning does not influence the HIF-1alpha protein expression and the adaptation. Severe hypoxic modes (HBH-7000, 8% O2) caused activation of lipid peroxidation processes in neocortex of hypoxia-sensitive rats. With the pro-oxidant systems dominating over the anti-oxidant ones, the neocortical expression of HIF-1alpha was found to decrease, which was accompanied by the impairment of the mechanisms of fast-response/long-term adaptation to hypoxia.

Selenium in medicine and treatment

Selenium, one of non-metals, has attracted great interest among many researchers over the last years. Properties of selenium were first mentioned back in the 12th century. Selenium exists in two forms, organic and inorganic one. But whatever the form of supplementation, it is an essential micronutrient conditioning many vital functions. Large-scale research has shown that it has many important properties, including antioxidant ones, for living organisms. It is incorporated in many enzymes and proteins. Numerous studies on this element have demonstrated its beneficial effects, mainly on the cardiovascular and nervous systems. It also contributes to reduction in the incidence of many neoplastic diseases. However, despite numerous desirable effects of this element in the human body, it should be remembered that selenium is also a toxic substance with a narrow therapeutic index. Its excessive consumption contributes to the development of a condition called selenosis. The recommended dose of selenium, depending on the patient’s age, ranges from 25 to 70 µg 24 h –1 . However, selenium in excess of 700 µg 24 h –1 shows strong toxicity. Therefore, adequate selenium supplementation is crucial. Nonetheless, despite numerous studies on selenium and its biological role, this trace element still raises many unresolved questions.

Plant-Derived Phenolics Inhibit the Accrual of Structurally Characterised Protein and Lipid Oxidative Modifications

Epidemiological data suggest that plant-derived phenolics beneficial effects include an inhibition of LDL oxidation. After applying a screening method based on 2,4-dinitrophenyl hydrazine- protein carbonyl reaction to 21 different plant-derived phenolic acids, we selected the most antioxidant ones. Their effect was assessed in 5 different oxidation systems, as well as in other model proteins. Mass-spectrometry was then used, evidencing a heterogeneous effect on the accumulation of the structurally characterized protein carbonyl glutamic and aminoadipic semialdehydes as well as for malondialdehyde-lysine in LDL apoprotein. After TOF based lipidomics, we identified the most abundant differential lipids in Cu++-incubated LDL as 1-palmitoyllysophosphatidylcholine and 1-stearoyl-sn-glycero-3-phosphocholine. Most of selected phenolic compounds prevented the accumulation of those phospholipids and the cellular impairment induced by oxidized LDL. Finally, to validate these effects in vivo, we evaluated the effect of the intake of a phenolic-enriched extract in plasma protein and lipid modifications in a well-established model of atherosclerosis (diet-induced hypercholesterolemia in hamsters). This showed that a dietary supplement with a phenolic-enriched extract diminished plasma protein oxidative and lipid damage. Globally, these data show structural basis of antioxidant properties of plant-derived phenolic acids in protein oxidation that may be relevant for the health-promoting effects of its dietary intake.

Different Impacts of Cardiovascular Risk Factors on Oxidative Stress

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN) were measured in mononuclear cells of controls (n = 20) and patients (n = 90) by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to control it.

Biological Activities of Essential Oils

Essential Oils (natural mixtures of single fragrance compounds) do possess biological properties. Besides psychological influences, these rather small and lipophilic molecules exhibit distinct physiological activities upon inhalation and/or topical administration which can be shown in animal experiments as well as in human studies. After a short introduction about the correct definition of the term „Essential Oils“ new research results on the application of fragrance compounds in therapy are presented. Examples of the biological properties of these natural compounds will be discussed and a great bow drawn from the effects on the human autonomic and central nervous system to „other effects“. These cover e.g. anti-inflammatory activities, anti-oxidative ones and penetration enhancing properties, anti-microbial and insect repellent activities and the possibility to use these small molecules in cancer prevention or therapy and against Alzheimer's disease. Some studies on the biochemical mechanism of such effects are also presented as well as methods to investigate the above activities of essential oils.

The use of some nanoemulsions based on aqueous propolis and lycopene extract in the skin's protective mechanisms against UVA radiation.

BackgroundThe use of natural products based on aqueous extract of propolis and lycopene in the skin's protective mechanisms against UVA radiation was evaluated by means of experimental acute inflammation on rat paw edema. The aim of the present study was to evaluate the harmlessness of propolis - lycopene system through evaluation of skin level changes and anti-inflammatory action. The regenerative and protective effect of the aqueous propolis and lycopene extract is based on its richness in biologically active substances such as: tocopherols, flavonoids, amino acids, polyunsaturated fatty acids, the chlorophyll pigment, all substances with strong antioxidant activity, that modify the oxidative stress, mainly by reducing the prooxidant processes and enhancing the antioxidant ones. These substances participate in the synthesis of prostaglandins and phospholipids components of cell membrane thus enhancing skin protection mechanisms.ResultsThe experimental systems offered a sustained release of the drug, in vitro, for aim eight hours. The prepared formulations aim did not reveal a deteriorating effect on tissues. They proved a better therapeutic efficiency Compared to standard suspension, they provided a better therapeutic efficiency coupled with extended time interval of tested parameters (24 hours). Preliminary examination of tissues showed that the experimental formulations did not irritate. Local application of propolis and lycopene aqueous extract nanoemulsion has a high potential both regarding its efficiency (the analgesic effect) and therapeutic safety.ConclusionsThis study demonstrates that propolis and lycopene extract nanoemulsions, preparations contains active substances, can confer better therapeutic effects than those of the conventional formulations, based on local control-release of dozed form, for a longer period of time, which probably improve its efficiency and skin acceptance, meaning a better compliance. The information obtained in the present study suggests that administration of propolis and lycopene aqueous extract nanoemulsion is safe. The preparation can be useful for further preclinical studies lycopene embedded in aqueous propolis extract to be used in pharmaceuticals (targeted medical therapy).

West-Libyan propolis and rosemary have synergistic anti-tumor effect against 12-O-tetradecanoylphorbol 13-acetate-induced skin tumor in BULB/C mice previously initiated with 7,12-dimethylbenz[a]anthracene

Background and aim: Many dietary constituents are chemopreventive in animal models and experiments with cultured cells are revealing various potential mechanisms of action. Many of these compounds can prevent, or greatly reduce, initiation of carcinogenesis, or can act on cell proliferation. In this study we examined the effects of topical application of propolis extract, rosemary extract and a mixture of both extracts together on 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion in mice previously initiated with 7,12-dimethylbenz[a]anthracene. Methods: The propolis extract, rosemary extract and a mixture of both extracts together were applied topically 15 min prior to the application of 5 nmol TPA for 20 weeks. Results: A decrease in the number of skin tumors per mouse by 27, 39, 71% was seen, as well as a decrease in the number of mice with tumors by 22, 31, 75% and inhibited the tumor size per mouse by 46, 62, 72% for propolis, rosemary and both together respectively. Also TUNEL data showed more increased incidence of TUNEL positivity among cancer cells in both topical applications together than their separate application on the back skin of mice. Conclusions: It is likely that the combination of their activities such as antioxidant and cytotoxic ones as well as the combination of several components in both are responsible for their inhibitory effect on carcinogenesis. Further investigations are recommended in order to establish the conditions under which topical application of propolis as well as rosemary produces either protective or deleterious effects.

Purification of commercial Alkannin and Shikonin samples

Alkannin, Shikonin (A/S) and their derivatives are potent pharmaceutical substances with a broad spectrum of biological activities like wound healing, antimicrobial, anti-inflammatory, anticancer and antioxidant ones [1,2]. As shown in our previous papers, most of the commercial samples of A/S and their derivatives, obtained either from natural products, or by synthesis or plant tissue cultures, are not purified since contain mainly monomeric, oligomeric A/S derivatives and other metabolites [3], and thus need further purification. This step is crucial for biological experiments of A/S derivatives, since many papers report the biological evaluation of commercial and not purified A/S samples. The conventional methods used for purification of A/S derivatives are column chromatography and recrystallization, but these are tedious and often require several steps. Therefore, there is need to develop an efficient method to purify A/S derivatives.

Is there a future for antioxidants in atherogenesis?

Antioxidants, preferentially those of dietary origin, have for a long time been considered to help against diseases that are presumably aggravated by oxidative stress, such as cardiovascular diseases, cancer, and neurodegenerative disorders. The outcome of clinical trials undertaken to corroborate this hypothesis, however, remained largely inconclusive. Evidence is now emerging that some dietary "antioxidants" influence signaling pathways and the expression of genes relevant in atherosclerosis by mechanisms other than antioxidative ones. By concrete examples we show that (1) vitamin E has gene regulatory functions which might be more important than acting as an antioxidant in vivo, (2) selenium itself is not an antioxidant at all, and even not in general when incorporated into glutathione peroxidases, and (3) a moderate oxidative stress is beneficial rather than detrimental since it can induce defense mechanisms counteracting xenobiotic and oxidative stress. Thus, there is only a future for antioxidants in the prevention of any disease if their real mechanism of action is considered and suitable read-outs and biomarkers are established.

Protective effect of Capparis spinosa on chondrocytes

The aim of the present study was to evaluate the in vitro chondroprotective effects of the lyophilised methanolic extract from flowering buds of Capparis Spinosa L (LECS). This plant, common to the Mediterranean basin, has been used by the traditional medicine for its diuretic and antihypertensive effects and also in certain pathological conditions related to uncontrolled lipid peroxidation. The extract contains many constituents, in particular some flavonoids (kaempferol and quercetin derivatives) and hydrocinammic acids with several known biological effects such as the anti-inflammatory and the antioxidant ones. In this study, we assayed the effect of LECS on human chondrocytes cultures stimulated by proinflammatory cytokine interleukin-1β (IL-1β) and we determined the production of key molecules released during chronic inflammatory events (nitric oxide, glycosaminoglycans, prostaglandins and reactive oxygen species). We observed that LECS was able to counteract the harmful effects induced by IL-1β. This protection appeared to be greater than that elicited by indomethacin, which is usually employed in joint diseases. Since LECS possess a chondroprotective effect, it might be used in the management of cartilage damage during the inflammatory processes.

Effect of catechin O-methylated metabolites and analogues on human LDL oxidation.

The effects of catechin metabolites and methylated analogues on LDL oxidation were studied in vitro using either a water-soluble initiator or copper ions to induce lipid peroxidation. Direct addition of catechin O-methylated analogues to the oxidation mixture led to a clear protective effect during lag phase and for the metabolites during both lag and propagation phases. The structure-activity relationships obtained with these selectively O-methylated compounds allowed determination of catechin active moietie: the catechol B-ring. Based on physical chemical studies, these results suggest that the mechanism implied in the scavenging properties of flavan-3-ols is not only hydrogen transfer, as generally described, but mainly an electronic transfer from the phenolate, and that 3'- and 4'-O-methylcatechin seem, moreover, to act as amphiphilic chain-breaking antioxidants. However, the plasma concentration of flavan-3-ols necessary to protect LDL is far greater than those usually found in human plasma. Therefore, the data do not support a direct physiological relevance of flavan-3-ols as antioxidants in lipid processes. Future research should focus on other effects besides simple antioxidant ones.

PACLITAXEL NEUROTOXICITY: ANTI‐APOPTOTIC EFFECT OF RESVERATROL

We have demonstrated in the SH‐SY5Y human neuroblastoma cell line that the antineoplastic drug paclitaxel induces apoptosis associated with the phosphorylation of c‐raf and Bcl‐2, thus causing Bcl‐2 inactivation. In addition, we have observed the cleavage of caspase 7 and PARP, and the involvement of JNK/SAPK cascade.In this study, we investigated the possible anti‐apoptotic effect of resveratrol on paclitaxel‐induced apoptosis. Resveratrol is a natural antioxidant occurring in grapes and wine that as been shown to have anticancer and anti‐inflammatory effects. Studies on the effect(s) of resveratrol on nervous cells are very few and limited to testing its ability in preventing oxidative stress in rat pheocromocytoma PC12 cells. However, the biological and pharmacological properties of resveratrol suggest that this natural compound might act on neuronal cells with a mode of action that is different from the antioxidant ones. To confirm this hypothesis, we studied the possible antagonist effect(s) of resveratrol on paclitaxel‐induced apoptosis pathways.Our results indicate that the simultaneous treatment of 50M resveratrol and 1M paclitaxel induces a significant reduction of the percentage of apoptotic cells in comparison with 1M paclitaxel alone. Furthermore, we have demonstrated that resveratrol treatment determines a significant reduction of the phosphorylation of c‐raf and Bcl‐2 and a partial reduction of cleavage of caspase 7 and PARP. Finally, we observed an evident reduction of activation of JNK/SAPK in the presence of resveratrol. On the contrary, resveratrol does not affect the tubulin polymerization induced by paclitaxel.In conclusion, our results suggest that resveratrol is able to partially antagonize a nonoxidative stress apoptotic stimulus by influencing the typical signal pathways involved in apoptosis.

Antimicrobial and Antioxidant Activities of Alkyl Hydroxycinnamates (Alkacins) in Model Systems and Food Products

Alkyl hydroxycinnamates (alkacins) were examined for antimicrobial and antioxidant activites in both model systems and food products. These were inhibitory to a wide range of bacteria and demonstrated marked inhibitory effects toward yeasts. The results were comparable to the effects of methyl and propyl paraben. S. cerevisiae was more resistant to the alkacins and to the parabens in apple juice than in an artificial medium, but several esters could prevent growth of the yeast at 250ppm. In ground beef the antimicrobial properties were not as well expressed as the antioxidative ones, but methyl caffeoate at 1,000ppm delayed spoilage and an increase in thiobarbituric acid value. When used as a dip solution for salmon muscle tissue, there was little or no inhibition of microbial spoilage. The results indicated that while these compounds have fair to very good activities in model systems, their relative activity in foods is specific to the food system.