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Biomedical subjects

A Bertelli

Publications and source records attributed to A Bertelli.

At least 19 recordsLinked to original sources

Comparison of cardioprotective abilities between the flesh and skin of grapes.

Recent studies have documented that grapes and grape juices are equally cardioprotective as red wine. The existing reports implicate that the skin and seeds of the grapes containing polyphenolic antioxidants are instrumental for the cardioprotective properties of grapes. The present study examines if the flesh of grapes also possesses any cardioprotective abilities. Three groups of randomly selected rats were fed, water only (control), flesh of the grapes (2.5 mg/kg b. wt.) or the skins (2.5 mg/kg b. wt.) for 30 days. At the end of the 30 days, isolated perfused hearts were made ischemic for 30 min followed by 2 h of reperfusion in the working mode. The results demonstrated that both flesh and skin of the grapes could protect the hearts from ischemic reperfusion injury as evidenced by improved postischemic ventricular recovery and reduced myocardial infarct size. High performance liquid chromatography (HPLC) revealed that skin and flesh contained comparative amounts of glucose, fructose, tartaric acid, malic acid, shikimic acid, and trans-caftaric acid. In addition, the flesh contained reduced amounts (compared to skin) of cis-coutaric, trans-coutaric, caffeic, p-coumaric, cinnamics, and catechin/epicatechin. Total polyphenolic index was also lower in flesh compared to skin. The anthocyanins were present exclusively in the skin. Electron paramagnetic resonance (EPR) spectrometry of hydroxy radicals indicated that both flesh and skins possessed equal amount of ROS scavenging activities. Total malonaldehyde content in the heart was reduced comparatively with either flesh or skin. The results indicate for the first time that the flesh of grapes are equally cardioprotective as skin, and antioxidant potential of skin and flesh of grapes are comparable with each other despite of the fact that flesh does not possess any anthocyanin activities.

Animals↗

The introduction of the stilbene synthase gene enhances the natural antiradical activity of Lycopersicon esculentum mill.

Tomato (Lycopersicon esculentum) is a vegetable rich in antioxidants, such as lycopene, lutein, and zeaxanthin. Their presence is responsible for the characteristic ability of this product to inhibit the formation of reactive oxygen species, including singlet oxygen. The grapes and wines derived from grapes also contain powerful antioxidants. The antioxidant effect is derived from the polyphenols such as resveratrol and proanthocyanidin. Resveratrol is phytoalexin that is synthesized via the activation of the gene, stilbene synthase (STS). We decided to determine if the introduction of this gene into Lycopersicon esculentum Mill could modify its antioxidant activity. Using Electronic Paramagnetic Resonance (EPR) spectroscopy, which permits the detection of antiradical activity, especially *OH (hydroxyl radical), we showed that the antioxidant activity of the products, into which the gene STS had been introduced, was almost double than that of natural products and that their activity was especially pronounced due to ripening. Moreover, resveratrol concentrations in modified tomatoes were much higher than that found in the individual fruit. In the isolated hearts subjected to ischemia/reperfusion, the rats fed with modified tomato exhibited better cardiac performance, reduced myocardial infarct size and decreased number of apoptotic cardiomyocytes, and reduced oxidative stress compared to unmodified tomato or resveratrol alone indicating superior cardioprotective abilities of modified tomatoes.

Acyltransferases↗

Evaluation of carnitine, acetylcarnitine and isovalerylcarnitine on immune function and apoptosis.

The pool of different carnitine derivatives is formed by carnitine, acetylcarnitine, propionylcarnitine and isovalerylcarnitine. Isovalerylcarnitine is a compound performing activities that differ from those of the other carnitine esters. Its activity on proteolytic enzymes and on the calpain system has been demonstrated in the past. Both the calpain and the caspase systems belong to the protease family and lead to cytochrome activation and apoptosis. The two systems can interact to promote apoptosis. In view of this proapoptotic activity of isovalerylcarnitine, studies were carried out to ascertain whether this carnitine derivative influences cell-reaction processes associated with apoptosis. U937 leukemic cells were selected for these studies because they are a well-established model for the assessment of cellular immune responses. In addition to nuclear morphologic alterations produced by apoptosis that can be detected by specific histochemical and microscopic methods, we also took other cell functions into consideration, such as phagocytosis, cell killing and cell growth, which are indices of immune function related to apoptosis. Unlike reference carnitine forms, isovalerylcarnitine produced an early and marked increase in phagocytosis and also an increase in cell killing. Cell proliferation was reduced. The hypothesis is set forth that isovalerylcarnitine may be a caspase-activating, proapoptotic factor that resembles various anticancer agents, which induce early apoptosis that coincides with early activation of caspase. This hypothesis is supported by the ability of isovalerylcarnitine to induce early phagocytosis and cell killing.

Acetylcarnitine↗

EPR evaluation of the antiradical activity of wines containing high concentrations of resveratrol.

The ability of two samples of red wine with different resveratrol concentrations to inhibit hydroxyl radicals (*OH) produced by a Fenton-type reaction was assessed using the method of electronic paramagnetic resonance (EPR). One sample was an autochthonous wine, Uvalino, which has a very high resveratrol concentration; the second was another red wine with a much lower resveratrol concentration. The ability of the sample of Uvalino wine to obstruct hydroxyl radicals was evident, but it wasn't much better than the ability of the sample of wine with a lower resveratrol concentration. The resveratrol concentration of wine is an important factor for the inhibition of the formation of free radicals, especially hydroxyl radicals; however, it is not the only one responsible for this property of wine. Resveratrol concentration can act synergically with other factors, such as polyphenols, which are also contained in wine and have antioxidant properties.

Drug Evaluation, Preclinical↗

Effects of uvalino, a new autochthonous wine, on the inhibition of the production of hydroxyl radicals.

In view of the high concentration of resveratrol found in a new autochthonous wine (Uvalino) and the notable antioxidant activity of this substance, we decided to assess whether this wine could inhibit the production of free radicals. Nowadays, free radicals are considered to be the most noxious factors for tissues, triggering the development of many diseases. The assessments were carried out using a direct and more precise technique, electronic paramagnetic resonance (EPR), which is able to detect the ability of an antioxidant agent to inhibit the formation of hydroxyl radicals (*OH), which are among the most noxious reactive oxygen species (ROS). The results show that Uvalino wine is able to eliminate ROS production almost completely. Consequently, it has beneficial effects on health in all the diseases in which ROS plays an important pathogenetic role.

Antioxidants↗

Biological activity of parrodienes, a new class of polyunsaturated linear aldehydes similar to carotenoids.

A new chemical named parrodienes has been extracted from parrots' plumage. From the chemical point of view, parrodienes are polyunsaturated aldehydes similar to carotenoids. On the basis of this similarity we organized some biological experiments to evaluate the inhibition of lipoperoxidation of cell membranes induced by CCl4, protection against ultraviolet rays, anti-inflammatory activity and protection from an increase of ornithine-decarboxylase as marker of tumoral skin alteration. The results of these experiments showed that unsaturated dienes (parrodienes) play an important role on the inhibition and prevention of many biological processes that are at the basis of different pathological disorders.

Aldehydes↗

Evaluation of the antioxidant activity of new carotenoid-like compounds by electron paramagnetic resonance.

The antioxidant activity of a novel series of derivatives with a carotenoid-like structure was studied. These derivatives have recently been isolated chemically as a result of studies on the pigments present in a particular species of birds, namely parrots. These novel derivatives, which are also called parrodienes, have been proved to possess interesting biological properties that differ from those that carotenoids are known to have. The objective of this study was to demonstrate the ability of these novel compounds to inhibit the formation of reactive oxygen species, especially their ability to block the formation of hydroxyl radicals, which are among the most reactive products of oxygen reactions and which produce the greatest damage to cells and tissues. The technique used to assess this antioxidant capacity of parrodienes was electron paramagnetic resonance, which allows direct assessment of inhibition of hydroxyl radical formation (.OH). The results show that these derivatives, especially octatriene, are able to exert evident antioxidant activity, thus confirming that their antioxidant properties are important for their biological activity.

Aldehydes↗

Evidence for resveratrol-induced preservation of brain mitochondria functions after hypoxia-reoxygenation.

We have previously shown, as have other authors, that trans-resveratrol (E-resveratrol, 3,4,5-trihydroxy-E-stilbene) reduces reactive oxygen species (ROS) generation of mitochondria freshly isolated from healthy rat brains and that it also counteracts the effect of uncouplers (CCCP) on mitochondrial respiration and oxidative phosphorylation. Two main mechanisms have been shown: firstly, a scavenger effect toward O2- and secondly inhibition of complex III ROS generation. We now report on the effects of resveratrol in a pathological model that mimics the ischemia followed by the reperfusion process which may occur in the human brain. Isolated brain mitochondria were submitted first to hypoxia then to reoxygenation. The aim of this study was to determine the extent of mitochondrial damage induced by this experimental model, to demonstrate which mitochondrial functions were altered and to quantify the extent to which they were prevented by resveratrol. Resveratrol was either added to mitochondria freshly isolated from healthy rat brains or was injected by subcutaneous chronically implanted pumps (0.5, 2 and 10 mg/kg/day for 7 days). The rats were then sacrificed and mitochondria were extracted from brains. To evaluate the respective effects of hypoxia and reoxygenation on mitochondrial functions and the relevant effects of resveratrol, this drug was added (first protocol) either before the complete process (i.e., hypoxia and reoxygenation), or after anoxia before reoxygenation. We found that resveratrol prevented alterations of mitochondrial functions. This substance partly counteracted the decrease in respiratory control and the increase in ROS generation. It fully inhibited the alteration of membrane fluidity and the mitochondrial step of the apoptotic process (evidenced by cytochrome c release and membrane potential collapse). The effects of resveratrol were concentration-dependent (in vitro) or dose-dependent (ex vivo, second protocol). They were not significantly different when the drug was added before or after hypoxia, which suggests that in this model, reoxygenation was the most deleterious process and the stage at which resveratrol was most effective.

Animals↗

Wine and tumors: study of resveratrol.

In modern industrial societies the attention to public health, especially in relation to food habits, is increasing day by day. Considering this, it's no wonder that wine, the voluptuary drink that best represents human history, is the most interesting compound. The main and best known wine effects on the human body are caused by alcohol, but several other active compounds are present in wine. Above all, resveratrol is able to neutralize free radicals, which can damage DNA and may lead to cancer onset. In this study, we have indagated resveratrol anticancer action, analyzing its effects on both cell cycle and growing of human lymphoma B (DHL-4) cells. MTT colorimetric test, tripan blue dye exclusion assay, and cell cycle analysis showed that resveratrol has a dose-dependent antiproliferative and antiapoptotic action on DHL-4 cells. These results confirm resveratrol's potential therapeutic role on tumors.

Antineoplastic Agents, Phytogenic↗

Cardioprotection with white wine.

The cardioprotective effects of red wine have been attributed to several polyphenolic antioxidants including resveratrol and proanthocyanidins. The goal of the present study was to determine whether white wines could also provide cardioprotection. Three different white wines (white wine #1, #2 and #3) were chosen for this study. Ethanol-free extracts of the wines were prepared by vacuum evaporation. Rats weighing approximately 200 g were given either 50 mg/kg or 100 mg/kg of each wine extract for 3 weeks. The rats were anesthetized and sacrificed and their hearts were excised for the preparation of isolated working rat heart. All hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function including heart rate, left ventricular developed pressure (LVDP), maximum first derivative of developed pressure (LVdp/dtmax), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEP), aortic flow (AF) and coronary flow (CF) were continuously monitored and myocardial infarct size was measured at the end of the experiments. The results of our study demonstrated that among the three different white wines, only white wine #2 conferred cardioprotection as evidenced by improved postischemic ventricular recovery compared with controls. The same white wine at a dose of 50 mg/kg also showed improvement in postischemic contractile recovery but the differences compared with controls were not significant. The amount of malondialdehyde production from these hearts was lower than that found in control hearts, indicating reduced formation of reactive oxygen species in white wine #2-treated rats. In vitro studies using a chemiluminescence technique revealed that white wine #2 scavenged both superoxide anions and hydroxyl radicals. The results of our study demonstrate that white wine #2 provided cardioprotection and the cardioprotective effect of the wine can be attributed, at least in part, to its ability to function as an in vivo antioxidant.

Animals↗

Effect of some white wine phenols in preventing inflammatory cytokine release.

Some well-known antioxidant phenols present in extravirgin olive oil have also been found in white wine. Both tyrosol and caffeic acid are phenols that are present not only in extravirgin olive oil, but also in wine, especially white wine. Their antioxidant properties are well known, but their biological effects have not yet been elucidated. In a previous study we found that these substances were able to inhibit tumor necrosis factor alpha release. The present study was carried out to assess whether these compounds are able to inhibit other inflammatory cytokines, such as interleukin-1 beta and interleukin-6. The results show that low concentrations of these phenols, which can be found in the bloodstream after intake of moderate quantities of white wine, exert significant inhibitory activity on the release of several inflammatory cytokines.

Antioxidants↗

Inhibitory activity of the white wine compounds, tyrosol and caffeic acid, on lipopolysaccharide-induced tumor necrosis factor-alpha release in human peripheral blood mononuclear cells.

The objective of this study was to assess whether tyrosol and caffeic acid are able to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha release. TNF is one of the most important cytokines involved in inflammatory reactions. The results show that both tyrosol and caffeic acid are able to inhibit LPS-induced TNF-alpha release from human monocytes, even at low doses. Their mechanisms of action are discussed and we conclude that high doses of the two compounds are not required to achieve effective inhibition of inflammatory reactions due to TNF-alpha release.

Caffeic Acids↗

Resveratrol, a polyphenol found in wine, reduces ischemia reperfusion injury in rat kidneys.

Reactive oxygen species have been implicated in the pathophysiology of renal ischemia reperfusion injury. Antioxidants including polyphenolics have been found to protect renal cells from the cellular injury induced by ischemia and reperfusion. Resveratrol, a stilbene polyphenol found in grapes and red wine, has recently been found to protect isolated rat heart from ischemia reperfusion injury. This study was sought to determine if resveratrol could also protect renal cells from ischemic injury. Male Wistar rats were treated with control, resveratrol (0.23 microg/kg), vehicle used to solubilize resveratrol, and resveratrol plus L-NAME (15 mg/kg body wt), a nitric oxide blocker. Our results demonstrated that resveratrol administration reduced the mortality of ischemic rats from 50% to 10% and renal damage was reduced as indicated by histologic examination and serum creatinine level. The short-term administration of resveratrol also inhibited renal lipid peroxidation induced by ischemia and reperfusion both in cortex and in medulla. Electron paramagnetic resonance detected an increased formation of nitric oxide in the resveratrol-treated kidney that was reduced to the baseline value after treating the rats with L-NAME in addition to resveratrol. The results suggest that resveratrol reduced the renal ischemia reperfusion injury through a nitric oxide-dependent mechanism.

Animals↗

Myocardial protection with red wine extract.

Cardioprotective action of red wine was studied by preperfusing isolated rat hearts with ethanol-free red wine extract for 15 min before subjecting them to 30 min of global ischemia followed by 2 h of reperfusion. Four other group of rats were studied under identical conditions, of which one served as control; one was treated with 10 microM trans-resveratrol (RVT), one of the major antioxidants found in red wines; another, with 0.07% ethanol; and another, with 0.07% ethanol plus 10 microM RVT. The results of our study demonstrated that both red wine extract and RVT were equally cardioprotective, as evidenced by their abilities to improve postischemic ventricular functions including developed pressure and aortic flow. Developed pressure values at 60 min after reperfusion were 81.8 +/- 1.2 and 68.8 +/- 4.1 mm Hg for the red wine extract and RVT groups, respectively, versus 49.7 +/- 2.7 mm Hg for the control group. These compounds also reduced myocardial infarct size compared with the control hearts (20.1 +/- 0.5% and 10.5 +/- 0.3% for red wine extract and RVT groups, respectively, vs. 29.9 +/- 3.1% for the control group). The ethanol-treated group displayed slightly better functional recovery, which deteriorated sharply toward the end of the reperfusion period, and the extent of infarction was comparable to that of the control group (31.5 +/- 0.9%). In the ethanol plus RVT group, postischemic contractile function was significantly better than control, and infarct size also was reduced to 20.9 +/- 0.7%. The amount of malonaldehyde formation in the postischemic myocardium was reduced by red wine extract and RVT, indicating a reduction of oxidative stress developed in the ischemic reperfused myocardium. In vitro studies revealed that red wine extract is a potent antioxidant as evidenced by its ability to scavenge peroxyl radical in vitro. Taken together, the results of our study indicate that red wines are cardioprotective by their ability to function as an in vivo antioxidant.

Animals↗

Opportunities in nutraceuticals.

The 3rd Vitafoods International Conference and Exhibition, held May 3-5, 2000, in Geneva, Switzerland, presented the latest findings and opportunities in the sector of nutraceuticals, dietary supplements and functional food. In addition to acetyl-L-carnitine and gamma-linolenic acid, the following products were highlighted: probiotics, proanthocyanadin, lutein and pectins. The future of this field will require that nutraceutical firms promote research at both the experimental and the clinical levels to convince medical doctors of the efficacy and health-promoting effects of these products.

Journal Article↗

The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury.

The consumption of red wine has been reported to impart a greater benefit in the prevention of coronary heart disease than the consumption of other alcoholic beverages. This beneficial effect is increasingly being attributed to certain antioxidants comprising the polyphenol fraction of red wine such as transresveratrol. In the present study, we investigated the potential cardioprotective effects of resveratrol in the face of ischemia reperfusion (I/R) injury. Isolated perfused working rat hearts after stabilization were perfused with Krebs-Henseleit Bicarbonate buffer (KHB) either in the presence or absence of transresveratrol (RVT) at a concentration of 10 microM for 15 min prior to subjecting them to 30 min of global ischemia followed by 2 h of reperfusion. Left ventricular functions were monitored at various timepoints throughout the reperfusion period to assess the extent of postischemic recovery in comparison with baseline values. Coronary perfusate samples were also collected to determine malonaldehyde (MDA) levels. The results demonstrated that RVT exhibited significant myocardial protection. This was evidenced by improved recovery of post-ischemic ventricular function including developed pressure and aortic flow as compared to the control group (KHB). Values for developed pressure in the RVT-treated group were significantly higher than those in the control group throughout the reperfusion period (71.09+/-4.88 mm Hg vs. 58.47+/-3.88 mm Hg, 68.87+/-5.07 mm Hg vs. 49.74+/-2.65 mm Hg and 51.67+/-3.95 mm Hg vs. 30.50+/-4.80 mm Hg at reperfusion timepoints R-15, R-60, and R-120, respectively). From R-30 onwards, aortic flow was markedly higher in the RVT treated group as compared with the control group, the differences being most significant at R-90 (32.45+/-2.19 ml/min vs. 19.83+/-1.62 ml/min) and R-120 (27.15+/-2.27 ml/min vs. 14.10+/-1.69 ml/min). In contrast to the KHB treated group, the RVT-treated group displayed significant reduction in MDA formation especially in the immediate early reperfusion period (63.71+/-8.19 pM/ml vs. 130.86+/-4.76 pM/ml, 63.84+/-15.62 pM/ml vs. 156.99+/-18.93 pM/ml, 71.29+/-2.80 pM/ml vs. 129.5+/-10.30 pM/ml and 56.25+/-5.79 pM/ml vs. 127.99+/-3.50 pM/ml at timepoints R-1, R-3, R-5, and R-7, respectively) indicating a reduction in I/R injury related oxidative stress. Infarct size was markedly reduced in the RVT group when compared with the control group (10.57+/-0.35% vs. 36.27+/-5.28%). In vitro studies revealed RVT to be a potent scavenger of peroxyl radicals suggestive of a probable mechanism involved in the protective ability of RVT. The results of this study indicate that resveratrol possesses cardioprotective effects which may be attributed to its peroxyl radical scavenging activity.

Animals↗

[Preliminary study of the relationship between the cardiopulmonary arrest time and its consequences in trauma patients].

The proposal of this research was to obtain parameters to start or maintain cardiopulmonary resuscitation (CPR) in victims of trauma. The duration of the cardiac arrest and the CPR of the survivors was described, as well as the cerebral performance and the mortality of these victims 24, 48 and 72 hours after these events had happened. With the results of this characterization the relation between duration of cardiac arrest time, CPR and mortality were described. Data for this report were collected in Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo emergency department. A big amount of the victims (93.4%) presents severe trauma and main cause of death was brain injury. Survival at 72 hours after CPR was 10%. The assessment, during the 72 hour period, of the survivors from cardiac arrest of traumatic cause has shown bad cerebral performance of those victims in that period of time. The survivor after the first episode of CPR was strongly related to cardiac arrest time when compared with CPR time. The time of cardiac arrest < or = 4 minutes and CPR < or = 20 minutes was related to survival more than 72 hours.

Adult↗