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Gastrointestinal cancers, particularly colorectal cancer, are mainly influenced by the dietary factor. A diet rich in fruits and vegetables can help to reduce the incidence of colorectal cancer thanks to the phenolic compounds, which possess antimutagenic and anticarcinogenic properties. Polyphenols, alongside their well-known antioxidant properties, also show a pro-oxidative potential, which makes it possible to sensitize tumor cells to oxidative stress. HO-1 combined with antioxidant activity, when overexpressed in cancer cells, is involved in tumor progression, and its inhibition is considered a feasible therapeutic strategy in cancer treatment. In this study, the effects of protocatechuic acid (PCA) on the viability of colon cancer cells (CaCo-2), annexin V, LDH release, reactive oxygen species levels, total thiol content, HO-1, γ-glutamylcysteine synthetase, and p21 expression were evaluated. PCA induced, in a dose-dependent manner, a significantly reduced cell viability of CaCo-2 by oxidative/antioxidant imbalance. The phenolic acid induced modifications in levels of HO-1, non-proteic thiol groups, γ-glutamylcysteine synthetase, reactive oxygen species, and p21. PCA induced a pro-oxidant effect in cancer cells, and the in vitro pro-apoptotic effect on CaCo-2 cells is mediated by the modulation of redox balance and the inhibition of the HO-1 system that led to the activation of p21. Our results suggest that PCA may represent a useful tool in prevention and/or therapy of colon cancer.

Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae) is widely used in traditional medicine. There is increasing interest on the in vivo protective effects of natural compounds contained in plants against oxidative damage caused from reactive oxygen species. In the present study the total phenolic and flavonoid contents of aqueous, methanol and dichloromethane extracts of leaves of Tithonia diversifolia (Hemsl.) A. Gray were determined; furthermore, free radical scavenging capacity of each extract and the ability of these extracts to inhibit in vitro plasma lipid peroxidation were also evaluated. Since oxidative stress may be involved in trasformation of pre-adipocytes into adipocytes, to test the hypothesis that Tithonia extract may also affect adipocyte differentiation, human mesenchymal stem cell cultures were treated with Tithonia diversifolia aqueous extract and cell viability, free radical levels, Oil-Red O staining and western bolt analysis for heme oxygenase and 5'-adenosine monophoshate-activated protein kinase were carried out. Results obtained in the present study provide evidence that Tithonia diversifolia (Hemsl.) A. Gray exhibits interesting health promoting properties, resulting both from its free radical scavenger capacity and also by induction of protective cellular systems involved in cellular stress defenses and in adipogenesis of mesenchymal cells.

The normal-weight obese (NWO) syndrome was identified in women whose body weight (BW) and BMI are normal but whose fat mass (FM) is >30%. In these subjects, an early inflammatory status has been demonstrated. The aim was to verify whether oxidative stress occurs in NWO. Sixty age-matched white Italian women were studied and subdivided as follows: 20 normal-weight individuals (NW) (BMI <25 kg/m(2); FM% <30%); 20 NWO (BMI <25 kg/m(2); FM% >30%); 20 preobese-obese (OB) (BMI >25 kg/m(2); FM% >30%). Anthropometric, body composition (by dual-energy X-ray absorptiometry) variables, plasma levels of some cytokines, reduced glutathione (GSH), lipid hydroperoxide (LOOH), nitric oxide (NO) metabolites (NO(2)(-)/NO(3)(-)), antioxidant nonproteic capacity (ANPC) were measured and compared between groups. Glucose and lipid metabolism parameters were assessed. GSH and NO(2)(-)/NO(3)(-) levels resulted lower in OB and NWO compared to NW (P < 0.01). LOOH levels resulted higher in OB and NWO (P < 0.01). ANPC in NWO was lower than NW but higher with respect to OB (P < 0.01). Correlation analysis revealed strong associations between GSH levels and BW, BMI, FM% (R = -0.45, at least P < 0.05); waist circumference (W) (R = -0.33, P < 0.05); FFM% (R = 0.45, P < 0.01); IL-1α, IL-6, IL-10, IL-15 (R = -0.39, -0.33, -0.36 -0.34, respectively, P < 0.05); triglycerides (R = -0.416, P < 0.05). LOOH levels were negatively related to FFM% (R = -0.413, P < 0.05) and positively to FM%, IL-15, TNF-α, insulin, total cholesterol, low-density lipoprotein cholesterol, and triglycerides (R = 0.408, R = 0.502, R = 0.341, R = 0.412, R = 0.4036, R = 0.405, R = 0.405, respectively, P < 0.05). The study clearly indicates that NWO, besides being in early inflammatory status, are contextually exposed to an oxidative stress related to metabolic abnormalities occurring in obesity.

Aerobic exercise increases free radical production as a consequence of enhanced oxygen consumption. If free radical formation exceeds antioxidant capacity, lipids, proteins, and DNA may be oxidized. Oxidative stress is widely recognized as a factor in many degenerative human diseases. The role of dietary antioxidants in protection against disease is a topic of continuing interest. In fact, there is epidemiological evidence correlating a higher intake of nutrients possessing antioxidant abilities with a lower incidence of various human diseases. This study was directed at investigating whether changes in plasma antioxidant capacity and oxidative stress markers occur in voluntary wheel runners, before and after oral supplementation with lycopene and isoflavones. For this purpose, plasma antioxidant capacity and oxidative stress markers were assessed in long distance runners at the end of a 60-minute run. Comparisons were made between runners before and after 60 days of supplementation with lycopene and isoflavones. DNA damage in blood cells of the same samples was also evaluated by comet assay. This investigation shows that oral supplementation with lycopene and soy-derived isoflavones significantly reduced lipid peroxidation and enhanced plasma nonproteic antioxidant defense.

Reactive oxygen species (ROS) could be important causative agents of a number of human diseases, including cancer. Thus, antioxidants, which control the oxidative stress state, represent a major line of defense regulating overall health. Human plasma contains many different nonenzymatic antioxidants. Because of their number, it is difficult to measure each of these different antioxidants separately. In addition, the antioxidant status in human plasma is dynamic and may be affected by many factors. Thus, the relationship between nonenzymatic antioxidant capacity of plasma and levels of well-known markers of oxidative stress (oxidized proteins, lipid hydroperoxides, decreases in thiol groups) better reflects health status. The present study considers antioxidant capacity and oxidative stress in human plasma of patients with colon cancer or precancerous lesions, as well as before and after surgical removal of tumors and/or chemo/radiation therapy. Healthy blood donors were used as controls. Colon cancer patients demonstrated a significant decrease in nonproteic antioxidant status and in total thiol groups with respect to healthy controls, whereas oxidized proteins and lipid hydroperoxide levels were significantly increased. In patients with precancerous lesions, the only unmodified parameter was the thiol group level. After surgery, the levels of oxidized proteins, lipid hydroperoxides, and total thiol groups were restored to those seen in healthy subjects, whereas nonproteic antioxidant capacity remained unmodified from that determined before surgery. Conversely, chemo/radiation therapy increased both nonproteic antioxidant capacity and levels of oxidized proteins and lipid hydroperoxides and significantly decreased total thiol groups. These results further support the hypothesis that oxidative stress correlates to the risk of some forms of cancer, not only in the initial stages but also during progression.

Cynara cardunculus subsp. sylvestris (wild artichoke) is widespread in Sicily, where it has been used for food and medicinal purposes since ancient times; decoctions of the aerial parts of this plant have been traditionally employed as a remedy for different hepatic diseases. In this study, the phenolic profile and cell-free antioxidant properties of the leaf aqueous extract of wild artichokes grown in Sicily (Italy) were investigated. The crude extract was also tested in cells for its antioxidant characteristics and potential oxidative stress inhibitory effects. To resemble the features of the early stage of mild steatosis in humans, human HepG2 cells treated with free fatty acids at the concentration of 1.5 mM were used. HPLC-DAD analysis revealed the presence of several phenolic acids (caffeoylquinic acids) and flavonoids (luteolin and apigenin derivatives). At the same time, DPPH assay showed a promising antioxidant power (IC50 = 20.04 ± 2.52 µg/mL). Biological investigations showed the safety of the crude extract and its capacity to counteract the injury induced by FFA exposure by restoring cell viability and counteracting oxidative stress through inhibiting reactive oxygen species and lipid peroxidation and increasing thiol-group levels. In addition, the extract increased mRNA expression of some proteins implicated in the antioxidant defense (Nrf2, Gpx, and SOD1) and decreased mRNA levels of inflammatory cytokines (IL-6, TNF-α, and IL-1β), which were modified by FFA treatment. Results suggest that the total phytocomplex contained in wild artichoke leaves effectively modulates FFA-induced hepatic oxidative stress. [ABSTRACT FROM AUTHOR]

The genus Teucrium (Lamiaceae) includes 300 species widespread all around the world, which are perennial herbs or shrubs commonly, named germanders. In Italy, Teucrium flavum L., Teucrium fruticans L., and Teucrium siculum Rafin are mostly present in Liguria, Sicily, and Sardegna. Teucrium species are characterized by mono and sesquiterpene hydrocarbons, flavonoids, fatty acid esters, and essential oils. Many species of this genus show antioxidant, antimicrobial, and antifungal activities, rendering them useful as natural preservative ingredients. In view of the interesting biological properties reported for Teucrium spp., in this study we determined the total phenol and flavonoid content of inflorescence extracts of T. flavum L., T. fruticans L., and T. siculum Rafin. In addition, we investigated the in vitro antioxidant and antibacterial activities of inflorescence extracts against pathogenic bacteria. Obtained results demonstrated that extracts had in vitro antioxidant activity and showed antimicrobial ability against Gram-positive and Gramnegative strains albeit with different effectiveness probably due to the different qualitative/quantitative composition of the extract also suggesting that these extracts might be useful in preventing several diseases in which oxidative stress may represent an important pathogenic mechanism. [ABSTRACT FROM AUTHOR]

Physical activity offers a paradoxical hormetic effect and a health benefit to cancer survivors; however, the biochemical mechanisms have not been entirely elucidated. Despite the well-documented evidence implicating oxidative stress in breast cancer, the association between health benefits and redox status has not been investigated in survivors who participate in dragon boating. The present study investigated the plasmatic systemic oxidative status (SOS) in breast cancer survivors involved in two distinct physical training exercises. A total of 75 breast cancer survivors were allocated to one of three groups: Control (resting), dragon boat racing and walking group; the latter is a type of aerobic conditioning exercise often advised to cancer patients. Various biochemical oxidative stress markers were examined, including oxidant status (hydroperoxide levels, lipid oxidation) and antioxidant status (enzymatic activities of superoxide dismutase and glutathione peroxidase, reduced glutathione levels and antioxidant capability). In addition, the individual DNA fragmentation and DNA repair capability of nucleotide excision repair (NER) systems were examined by comet assays. According to the results, all patients exhibited high levels of oxidative stress. Physical activity maintained this oxidative stress condition but simultaneously had a positive influence on the antioxidant component of the SOS, particularly in the dragon boat racing group. DNA fragmentation, according to the levels of singleand double-strand breaks, were within the normal range in the two survivor groups that were involved in training activities. Radiation-induced damage was not completely recognised or repaired by NER systems in any of the patients, probably leading to radiosensitivity and/or susceptibility of patients to cancer. These findings suggest that physical activity, particularly dragon boat racing, that modulates SOS and DNA repair capability could represent a strategy for enhancing the quality of life and improving the long-term health benefits for breast cancer survivors. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a mycotoxin involved in the development of different types of cancers in rats, mice and humans. A growing number of in vitro and in vivo studies has been collected and has described evidence compatible with a role for oxidative stress in OTA toxicity and carcinogenicity. Because the contribution of the oxidative stress response in the development of cancers is well established, a role in OTA carcinogenicity is plausible. Several studies have been performed to try to counteract the adverse effects of oxygen radicals generated under OTA-exposure. A number of molecules with various antioxidant properties were tested, using in vivo or in vitro models. Protection against OTA-induced DNA damage, lipid peroxidation, as well as cytotoxicity were observed, further confirming the link between OTA toxicity and oxidative damage. These studies demonstrated that antioxidants are able to counteract the deleterious effects of chronic consumption or exposure to OTA and confirmed the potential effectiveness of dietary strategies to counteract OTA toxicity. [ABSTRACT FROM AUTHOR]

Acquaviva R, Lanteri R, Li Destri G, Caltabiano R, Vanella L, Lanzafame 8, Di Cataldo A, Li Volti G, Di Giacomo C. Beneficial effects of rutin and L-arginine coadministration in a rat model of liver ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 296: G664-G670, 2009. First published December 24, 2008; doi: 10.1152/ajpgi.90609.2008.-Reperfusion following liver ischemia results in oxidative stress leading to liver injury. The aim of this study was to investigate the combined effects of two antioxidant agents, rutin and L-arginine, in rat liver ischemia-reperfusion (I/R). Male Wistar rats were divided into five groups: 1) sham operated, 2) hR. 3) hR + rutin, 4) hR + L-arginine, and 5) YR + rutin + L-arginlne. Plasmatic and hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA fragmentation and liver histopathology. Furthermore, to elucidate the pathophysiological processes involved in the antioxidant mechanism(s) of rutin and L-arginine, we assessed the expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing key roles in the biochemical cascade of liver injury. Significant increase in plasmatic ALT and AST activities were observed in untreated YR rats compared with sham-operated animals, whereas treatment with rutin or L-arginine in YR rats reduced hepatic damage. Interestingly, combined therapy with rutin and Larginine resulted in a further reduction of plasmatic ALT and AST activities compared with rutin or L-arginine alone. These results were further confirmed by the analysis of DNA fragmentation, LOOH, RSH groups, and liver histopathology, which showed the highest protective effects following the coadministration of rutin and Larginine. Finally, the combined therapy protocol resulted in a significant induction of liver HO-1 and a concomitant reduction of iNOS expression that may both be responsible for the beneficial effects of the proposed pharmacological protocol. [ABSTRACT FROM AUTHOR]

Pathophysiological mechanisms correlating diabetes mellitus with associated complications are still not completely clear, even though oxidative stress seems to play a pivotal role. Literature data suggest that cell damages induced by hyperglycemia, although multifactorial, have a common pathway in oxidative/nitrosative stress. The present study evaluated the effects of Betula etnensis Raf. bark extract, a plant belonging to the Betulaceae family endemic to Sicily, on oxidative stress and in preventing and/or retarding diabetes-associated complications in streptozotocin diabetic rats treated with the extract at dose of 0.5 g/kg body weight per day for 28 consecutive days. The extract administration significant decreased food and water intake, fasting blood glucose, weight loss and polyuria, compared with untreated diabetic animals. Furthermore, oxidative stress markers particularly, lipid hydroperoxides (LOOH) and nitrite/nitrate levels, non-proteic thiol groups (RSH), γ-glutamyl-cysteine-synthetase (γ-GCS) activities and expression, heme oxygenase-1 (HO-1), endothelial and inducible nitric oxide synthases (i-NOS e-NOS) expression, significantly changed by streptozocin treatment, were markedly restored both in plasma and tissues together with nuclear sirtuins activity (Sirt1). Results suggested that B. etnensis bark alcoholic extract is able to counteract oxidative stress and to ameliorate some general parameters related to diabetes. [ABSTRACT FROM AUTHOR]

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr®) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma. [ABSTRACT FROM AUTHOR]

Betula etnensis Raf. (Birch Etna) belonging to the Betulaceae family grows on the eastern slope of Etna. Many bioactive compounds present in Betula species are considered promising anticancer agents. In this study, we evaluated the effects of B. etnensis Raf. bark methanolic extract on a human colon cancer cell line (CaCo2). In order to elucidate the mechanisms of action of the extract, cellular redox status, cell cycle, and heme oxygenase-1 (HO-1) expression in ferroptosis induction were evaluated. Cell viability and proliferation were tested by tetrazolium (MTT) assayand cell cycle analysis, while cell death was evaluated by annexin V test and lactic dehydrogenase (LDH) release. Cellular redox status was assessed by measuring thiol groups (RSH) content, reactive oxygen species (ROS) production, lipid hydroperoxide (LOOH) levels and (γ-glutamylcysteine synthetase) γ-GCS and HO-1 expressions. The extract significantly reduced cell viability of CaCo2, inducing necrotic cell death in a concentration-depending manner. In addition, an increase in ROS levels and a decrease of RSH content without modulation in γ-GCS expression were detected, with an augmentation in LOOH levels and drastic increase in HO-1 expression. These results suggest that the B. etnensis Raf. extract promotes an oxidative cellular microenvironment resulting in CaCo2 cell death by ferroptosis mediated by HO-1 hyper-expression. [ABSTRACT FROM AUTHOR]

A correction to the article "Oxidative Stress in Normal-Weight Obese Syndrome" is presented.

Abstract: Diabetes mellitus is associated with a higher oxidative stress and reduced activity of the antioxidant defense system in different brain regions. Results from numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents. It is well established that polyphenols exert potent antioxidant and protective functions. Based on recent findings, one potential target for the antioxidant/antinflammatory properties of polyphenols is the heme oxygenase (HO)-1 pathway. Among various compounds tested silibinin, the main component of silymarin, has been shown to possess a strong antioxidant effect in various experimental models; however a study on the possible neuroprotective effect of this compound on the brain of diabetic animals is currently lacking. Therefore, we studied and measured in lean mice (db/m) and knock out mice for the leptin receptors mice (db/db) the effect of silibinin on HO-1 protein levels, non proteic thiol groups, isoprostanes and 8-OH deoxyguanosine (markers of lipid peroxidation and DNA damage, respectively) in different brain regions. Our results showed that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition. [Copyright &y& Elsevier]