Vanillylmandelic acid protects against reperfusion injury in an experimental animal model of myocardial infarction.

Vanillylmandelic acid, a catecholamine end-metabolite, has been shown to have several biological properties in previous studies, despite considered biologically inactive. We examined the potential effects of vanillylmandelic acid on the ischemic heart following myocardial infarction and reperfusion on a rat model. Thirty-four female Wistar rats were randomized into two groups, control and experimental. They were anesthetized and subjected to myocardial infarction through left anterior descending artery ligation. A previously studied dose of vanillylmandelic acid (10 mg/kg) was administered and the following parameters were studied during ischemia and reperfusion: a) mortality b) severity of ventricular tachyarrhythmias c) premature ventricular contractions and d) heart rate. Administration of vanillymandelic acid significantly reduced the severity of ventricular tachyarrhythmias and mortality rate during reperfusion, while it did not affect any other of the parameters studied. In conclusion, reperfusion injury was blunted through vanillylmandelic acid administration, which seems to be mediated by parasympathetic activation.

Correlation of bioelectrical impedance analysis phase angle with changes in oxidative stress on end-stage renal disease patients, before, during, and after dialysis.

Chronic kidney disease is a condition that promotes oxidative stress. There are conflicting evidence about the role of hemodialysis on oxidative stress, that are mostly related with the various types of membrane materials used, the quality and type of dialysate, the method used, etc. The phase angle (PhA), which is determined with bioelectrical impedance analysis (BIA), measures the functionality of cell membranes. In this study, the correlation of the PhA with parameters of oxidative stress is attempted for the first time. We evaluated parameters of oxidative status as total antioxidant capacity (TAC) in erythrocytes (RBCs) and plasma of patients with ESRD undergoing hemodialysis with low flux synthetic polysulfone membranes. Measurements were recorded from 30 patients (16 men and 14 women) aged 64 ± 14 years before, during, and after dialysis, and in 15 healthy volunteers aged 56 ± 12 years The PhA was obtained by BIA. The plasma TAC increased significantly (41%, p < 0.05). Intracellular TAC noted a non-significant increase. Total antioxidant capacity of the patients before and after hemodialysis was significantly lower from the healthy volunteers (p < 0.05) showing that ESRD patients are at the state of increased oxidative stress. The PhA increased in significantly positive correlation with plasma TAC at the end of hemodialysis. The process of hemodialysis with biocompatible synthetic membranes and bicarbonate dialysate improved plasma TAC. The positive correlation of PhA with extracellular TAC could evolve to a method of oxidative stress estimation by BIA but further research is needed.

Analgesic effect of the electromagnetic resonant frequencies derived from the NMR spectrum of morphine.

Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p < 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid.

Platelets aggregation around migrating tumor cells offers protection against the cytotoxic activity of the natural killers cells (NKC). The ascorbic acid in 3 x 10(-3) M concentration completely inhibited platelet aggregation, decreased thromboxane B2 levels, and inhibited the expression of platelet membranic receptor GpIIb/IIIa in non stimulated platelets, and increased the NKC cytotoxicity in an average rate of 105, 61, and 285% in the NKC/targets cells ratios 12.5:1, 25:1 and 50:1 respectively. The results suggest the role of ascorbic acid in increasing the susceptibility of tumor cells to NKC; the ascorbic acid could be used as part of a multidrug therapy to treat diseases which up to now have been treated only through chemotherapy.

Functionality of natural killer cells from end-stage cancer patients exposed to coherent electromagnetic fields.

The main objective of our study is to investigate whether an enhancement of the immune system in end-stage cancer patients is achieved by exposure to coherent electromagnetic fields. For this reason, 15 end-stage cancer patients were exposed at low intensity, coherent electromagnetic fields at radiofrequencies ranging from 600 kHz-729 Hz, for 8 h/day, 6 days/week for 4 weeks. NKs number and cytotoxicity of NK T-lymphocytes versus K562 cancer cell line were estimated by flow cytometry, before and after exposure. Data showed that the exposure of the end-stage cancer patients to the coherent electromagnetic fields resulted in a significant increase of the number and the cytotoxicity of the NK T-lymphocytes against cancer cells, in all patients. Exposure to coherent EMFs at radiofrequencies increases the number and cytotoxicity of NK T-lymphocytes, which may contribute to the improvement of cancer patients' status.

Criterion-related validity of the short International Physical Activity Questionnaire against exercise capacity in young adults.

BACKGROUND: Self-reported physical activity (PA) is well associated with cardiorespiratory fitness and exercise capacity. The short International Physical Activity Questionnaire (IPAQ-short) is a frequently used instrument for cross-national assessments of PA in adults. The purpose of this study was to validate IPAQ-short against exercise capacity in Greek young adults. DESIGN AND METHODS: One hundred and thirteen men and 105 women, aged 20-29 years, were randomly selected from a larger population of young health-science students. A Greek version of IPAQ-short (IPAQ-Gr) was administered to all participants before their exercise capacity evaluation with a maximal Bruce treadmill test. Multiple regression and correlation analyses were used to examine the associations between all IPAQ-Gr outcomes with exercise capacity based on maximal treadmill time. RESULTS: Spearman's correlations for total and vigorous PA against maximal treadmill time were significant in all groups examined, ranging from 0.35 to 0.43. Moderate and walking PA correlations were poor and nonsignificant, ranging from near-zero values to 0.19. In multiple linear regression analysis, only sex, smoking, and vigorous PA from all personal and log-transformed IPAQ-Gr data were significantly associated with maximal treadmill time. Partial correlation analysis for the overall population, adjusted for sex and smoking, showed that total PA (r=0.37) and vigorous PA (r=0.47) were significantly associated with exercise capacity. CONCLUSION: IPAQ-Gr was tested against exercise capacity and showed acceptable validity properties in Greek young adults. Total and vigorous weekly PA expenditure were well associated with exercise capacity, presenting significant validity correlations against maximal treadmill time.

A facile approach to hydrophilic oxidized fullerenes and their derivatives as cytotoxic agents and supports for nanobiocatalytic systems.

A facile, environment-friendly, versatile and reproducible approach to the successful oxidation of fullerenes (oxC60) and the formation of highly hydrophilic fullerene derivatives is introduced. This synthesis relies on the widely known Staudenmaier's method for the oxidation of graphite, to produce both epoxy and hydroxy groups on the surface of fullerenes (C60) and thereby improve the solubility of the fullerene in polar solvents (e.g. water). The presence of epoxy groups allows for further functionalization via nucleophilic substitution reactions to generate new fullerene derivatives, which can potentially lead to a wealth of applications in the areas of medicine, biology, and composite materials. In order to justify the potential of oxidized C60 derivatives for bio-applications, we investigated their cytotoxicity in vitro as well as their utilization as support in biocatalysis applications, taking the immobilization of laccase for the decolorization of synthetic industrial dyes as a trial case.

Effects of secondary biological treatment plant effluent administration, as drinking water, to rats' urogenital system in relation to cadmium and lead accumulation.

The aim of this study was to examine the effect of the secondary biological treatment plant effluent administration on the kidneys, urinary bladder, and testis of Wistar rats in relation to lead (Pb) and cadmium (Cd) accumulation, since such an effluent is used for irrigation of edible plants. Male Wistar rats, randomly assigned into 5 groups, were treated with domestic sewage effluent (DSE) for 24 months. Cadmium and lead concentrations in the DSE, rats' tissues, and urine were estimated by means of atomic spectroscopy. Lead was rapidly accumulated in high amounts in rats' kidney and to a lesser extent in the testis whereas Cd concentration was raised in all tissues examined. Deposition of Cd and Pd in the kidney of the rats resulted in profound damage over time. The results showed that long-term administration to DSE as drinking water exposes living organisms to urogenital stress related to heavy metal concentration and pH of the effluent.

Impact of enterococcal urinary tract infections in immunocompromised - neoplastic patients.

Infections in immunocompromised-neoplastic patients represent a severe complication. Among bacteria, Enterococcus species constitute a common causative pathogen of urinary tract infections (UTIs), especially among hospitalized patients with or without urinary tract carcinoma, related commonly to urinary tract abnormalities, urinary catheters or prolonged antibiotic treatment. Although enterococci have been considered more commonly as colonization bacteria in the intestine than virulent agents, they are frequently implicated in UTIs. The high incidence of enterococcal UTIs is associated with several risk factors including age, female gender, previous UTI, diabetes, pregnancy, immunosuppression due to cancer development and progression, renal transplantation and spinal cord injury. Clinical manifestations are usually absent or mild in enterococcal UTIs, which may also become an important source for both bacteremia and endocarditis. Over the last years, the prevalence of multidrug resistant enterococci, particularly vancomycin-resistant E. faecium and E. faecalis has significantly risen worldwide, associated with increased morbidity, limited treatment options and increased health-care costs. In this review, the current knowledge on enterococcal UTIs epidemiology and influence in the corresponding immunocompromised patients is highlighted.

Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats.

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney's relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats' blood and malondialdehyde levels in rats' urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood's antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons' histology from cisplatin's toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.

Antitumor effects of the electromagnetic resonant frequencies derived from the 1H NMR spectrum of Ph3Sn(Mercaptonicotinic)SnPh3 complex.

The aim of this article is to investigate the potential cytotoxic and antitumor effects of the resonant electromagnetic fields (rEMFs) derived from the 1H NMR spectrum of the Ph3Sn(Mercaptonicotinic)SnPh3 complex (SnMNA). The ability of the complex's rEMFs to induce leiomyosarcoma (LMS) cell death and to recess tumor (leiomyosarcoma) development in Wistar rats was evaluated. The effects of the simultaneous administration of the SnMNA complex at extremely low concentrations and exposure to its rEMFs was also investigated. The emission of the 1H NMR spectrum of the complex alone or in a combination with low ineffective doses of the complex decreased LMS cell viability mainly through apoptosis. Moreover, the results from the in vivo experiments showed a significant prolongation of life expectancy in tumor-bearing rats exposed to the rEMFs alongside a deceleration in tumor growth rate. We speculate that the rEMFs of a biologically active substance could exert similar biological effects as the substance itself, mainly when is combined with extremely low ineffective concentrations of the substance.

The course of dyskinesia induction by different treatment schedules of levodopa in Parkinsonian rats: is continuous dopaminergic stimulation necessary?

The aim of the present study was to investigate the course of levodopa induced dyskinesia (LID) development in parkinsonian rats treated with several different levodopa dosing regiments. Administration of 6.25 mg/kg levodopa once daily did not induce any dyskinesia for the first 12.5 +/- 2.5 days. Then, LID gradually increased in intensity reaching an AIMs score on day 40 of 6.3 +/- 0.9. Treatment with 6.25 mg/kg of levodopa qid resulted in the rapid appearance of LID with a mean latency of 2 days and an AIMs score of 19.9 +/- 2.9 on day 10. Levodopa (25 mg/kg) once daily induced severe LID from the second day of treatment reaching an AIMs score of 35 +/- 3.2. In summary, the worst way for delivering levodopa was through intermittent administration of high doses. The daily cumulative dose of levodopa was found more important for LID induction than the total amount of levodopa received. In contrast, the best way to administer levodopa in respect to prevention/delay of LID was "low dopaminergic stimulation" with one low daily dose, instead of trying to achieve "continuous dopaminergic stimulation" using several levodopa doses throughout the day. The benefits of this strategy offered protection against severe dyskinesia even if subsequently subjects were switched to high dose levodopa.

Modulation of cisplatin cytotoxic activity against leiomyosarcoma cells by epigallocatechin-3-gallate.

The aim of this study was to investigate the cytotoxic effect cisplatin in combination with epigallocatechin-3-gallate (EGCG) on leiomyosarcoma cells (LMS cells) in order to identify a less toxic but equally effective alternative. Assays for cell proliferation, colony formation efficiency, induction of apoptosis and cell cycle arrest were performed using the IC50 of cisplatin (8.6 µΜ) as a reference value and a concentration of EGCG (30 µΜ) that caused a non-significant reduction in cell proliferation. Pre-treatment of cells with EGCG for 24 h before the addition of cisplatin increased cytotoxicity up to 8.5% (p < 0.05) and the number of apoptotic cells by 40%. Epigallocatechin-3-gallate failed to alter S-phase cell cycle arrest induced by cisplatin and to modulate cisplatin effects on mitochondrial function. These results indicate that pre-treatment with EGCG could be used as an adjunctive therapy to maximise effectiveness of chemotherapy.

Anticancer effects on leiomyosarcoma-bearing Wistar rats after electromagnetic radiation of resonant radiofrequencies.

In the present study, the effects of a resonant low intensity static electromagnetic field (EMF), causing no thermal effects, on Wistar rats have been investigated. Sarcoma cell lines were isolated from leiomyosarcoma tumors induced in Wistar rats by the subcutaneous (s.c) injection of 3,4-benzopyrene. Furthermore, smooth muscle cells (SMC) were isolated from the aorta of Wistar rats and cultivated. Either leiomyosarcoma cells (LSC) or SMC were used to record a number of characteristic resonant radiofrequencies, in order to determine the specific electromagnetic fingerprint spectrum for each cell line. These spectra were used to compose an appropriate algorithm, which transforms the recorded radiofrequencies to emitted ones. The isolated LSC were cultured and then exposed to a resonant low intensity radiofrequency EMF (RF-EMF), at frequencies between 10 kHz to 120 kHz of the radiowave spectrum. The exposure lasted 45 consecutive minutes daily, for two consecutive days. Three months old female Wistar rats were inoculated with exposed and non-exposed to EMF LSC (4 x 10(6) LCS for animal). Inoculated with non-exposed to EMF cells animals were then randomly separated into three Groups. The first Group was sham exposed to the resonant EMF (control Group-CG), the second Group after the inoculation of LSC and appearance of a palpable tumor mass, was exposed to a non-resonant EMF radiation pattern, for 5 h per day till death of all animals (experimental control Group-ECG). The third Group of animals after inoculation of LSC and the appearance of a palpable tumor mass, was exposed to the resonant EMF radiation for 5 h per day, for a maximum of 60 days (experimental Group-I, EG-I). A fourth Group of animals was inoculated with LSC exposed to EMF irradiation and were not further exposed to irradiation (experimental Group-II, EG-II). Tumor induction was 100% in all Groups studied and all tumors were histologically identified as leiomyosarcomas. In the case of the EG-I, a number of tumors were completely regretted (final tumor induction: 66%). Both Groups of animals inoculated with exposed or non-exposed to the EMF LSC, (EG-I and EG-II, respectively) demonstrated a significant prolongation of the survival time and a lower tumor growth rate, in comparison to the control Group (CG) and the experimental control Group (ECG). However, the survival time of EG-I animals was found to be significantly longer and tumor growth rate significantly lower compared to EG-II animals. In conclusion, our results indicate a specific anticancer effect of resonant EMF irradiation. These results may possibly be attributed to (a) the duration of exposure of LSC and (b) the exposure of the entire animal to this irradiation.

Effects of N-methyl-D-aspartate receptor antagonism on neuroleptic-induced orofacial dyskinesias.

RATIONALE: Tardive dyskinesia is a syndrome of abnormal, involuntary movements, which occurs as a complication of long-term neuroleptic therapy. The pathophysiology of this potentially irreversible syndrome is still an enigma. OBJECTIVE: The objective of the present study was to elucidate the role of N-methyl-D-aspartate (NMDA) receptor involvement in neuroleptic-induced orofacial dyskinesia in rats. METHODS: Animals chronically treated with haloperidol for a period of 40 weeks exhibited significantly more vacuous chewing movements (VCMs), as compared to vehicle-treated controls. In a series of acute experiments, rats received: amantadine (10, 20, and 40 mg/kg i.p.), a low-affinity, uncompetitive NMDA-receptor antagonist (open channel blocker); dextrorphan (5, 10, and 20 mg/kg i.p.), an NMDA receptor channel antagonist; ifenprodil (2.5, 5, and 10 mg/kg i.p.), a noncompetitive allosteric NMDA receptor antagonist acting at the polyamine site; and Ro 25-6981 (2.5, 5, and 10 mg/kg i.p.), a potent and selective blocker of NMDA receptors which contain the NR2B subunit. RESULTS: All the drugs tested, except dextrorphan, reduced VCMs and tongue protrusions with varying efficacies and side effects profiles. Ro 25-6981 was found significantly more potent than amantadine and ifenprodil in reducing VCMs and tongue protrusions at all doses tested, and at the higher dose, it completely eliminated orofacial dyskinesia (p<0.05). CONCLUSIONS: These results suggest that NMDA receptors may play a significant role in the pathophysiology of tardive dyskinesia. Furthermore, antagonists showing selectivity for NMDA receptors containing the NR2B subunit may be particularly efficacious as novel therapeutic agents for the treatment of tardive dyskinesia and deserve further testing.

Effects of low intensity static electromagnetic radiofrequency fields on leiomyosarcoma and smooth muscle cell lines.

In this study we investigated the effects of low intensity static radiofrequency electromagnetic field (EMF) causing no thermal effects, on leiomyosarcoma cells (LSC), isolated from tumors of fifteen Wistar rats induced via a 3,4-benzopyrene injection. Electromagnetic resonance frequencies measurements and exposure of cells to static EMF were performed by a device called multi channel dynamic exciter 100 V1 (MCDE). The LSC were exposed to electromagnetic resonance radiofrequencies (ERF) between 10 kHz to 120 kHz, for 45 min. During a 24h period, after the exposure of the LSC to ERF, there was no inhibition of cells proliferation. In contrast, at the end of a 48 h incubation period, LSC proliferation dramatically decreased by more than 98% (P<0.001). At that time, the survived LSC were only 2% of the total cell population exposed to ERF, and under the same culture conditions showed significant decrease of proliferation. These cells were exposed once again to ERF for 45 min (totally 4 sessions of exposure, of 45 min duration each) and tested using a flow cytometer. Experiments as above were repeated five times. It was found that 45% of these double exposed to ERF, LSC (EMF cells) were apoptotic and only a small percentage 2%, underwent mitosis. In order to determinate their metastatic potential, these EMF cells were also counted and tested by an aggregometer for their ability to aggregate platelets and found to maintain this ability., since they showed no difference in platelet aggregation ability compared to the LSC not exposed to ERF (control cells). In conclusion, exposure of LSC to specific ERF, decreases their proliferation rate and induces cell apoptosis. Also, the LSC that survived after exposed to ERF, had a lower proliferation rate compared to the LSC controls (P<0.05) but did not loose their potential for metastases (platelet aggregation ability). The non-malignant SMC were not affected by the EMF exposure (P<0.4). The specific ERF generated from the MCDE electronic device, used in this study, is safe for humans and animals, according to the international safety standards.

Association of high blood pressure with body mass index, smoking and physical activity in healthy young adults.

INTRODUCTION: The purpose of this study was to examine the associations between resting blood pressure (BP), smoking, physical activity (PA) and body mass index (BMI) in Greek young adults. MATERIALS AND METHODOLOGY: A standardised questionnaire and the Greek version of IPAQ-short were given to 1500 randomly selected health science students, in order to record smoking behaviour, PA status, BMI and resting BP. All healthy young adults aged 19-30 years old were eligible. The final size of the study cohort was 1249 students (522 men). RESULTS: Males' BP was 129.2/77.0 mmHg, significantly higher than the females' values of 119.9/73.4 mmHg. Approximately 17% of the total population were classified as overweight and 3% as obese. In the overall population, smoking prevalence was 35.2%, with 15.3% being heavy smokers (≥21 cigs/d). Smoking prevalence did not differ significantly between sexes. The prevalence of health-enhancing PA (high PAclass) was only 14.0%, while 42.8% of the study population were classified as insufficiently active (low PAclass). Of the three lifestyle risk factors examined, only BMI was significantly and directly associated with systolic and diastolic BP levels. The prevalence of hypertension (≥140/90 mmHg) was significantly higher in men compared to women, and in obese and overweight participants compared to normal-weight subjects. Smoking and categorical PA (PAclass) were not correlated with BP. Continuous vigorous PAscore was significantly and directly associated with systolic BP, but only in males. CONCLUSION: BMI was significantly and directly associated with resting BP in both sexes. Smoking prevalence and PA status were not associated with BP in this sample of Greek young adults.

The healing effect of four different silver complexes on full-thickness skin burns in a rat model.

AIM: This study was carried-out to investigate the effect of four different silver substances (S1, S2, S3, and S4) on burn wound healing in a rat model. MATERIALS AND METHODS: One hundred and eighty Wistar rats were used. Animals were randomized into six groups to receive no treatment (CG, control group), and local application of the solvent of silver substances (SG, solvent group), as well as of the four silver substances (EG1-EG4 groups for substances S1-S4, respectively). On days 0, 3, 6, 12, 21, and 31 following burn wound infliction, the size and healing progress of each wound were recorded and evaluated by means of clinical evaluation, planimetry and histological examination. RESULTS: According to our findings lower infection rates, as well as significantly accelerated wound healing and faster re-epithelialization were recorded in EG1, EG2, and EG4 compared to the other groups. DISCUSSION: The use of S1, S2, and S4 substances proved to be an effective treatment of burn wounds that ensured better outcomes compared to the control and solvent groups, as well as with the use of S3 substance. Nevertheless, they failed to produce short-term healing of the full-thickness burn. Further research is required to examine the possibility of speeding the treatment of full-thickness burns by these complexes in order to reduce healing time to acceptable limits and prevent the need for surgery.

Vanadium in cancer treatment.

Vanadium compounds exert preventive effects against chemical carcinogenesis on animals, by modifying, mainly, various xenobiotic enzymes, inhibiting, thus, carcinogen-derived active metabolites. Studies on various cell lines reveal that vanadium exerts its antitumor effects through inhibition of cellular tyrosine phosphatases and/or activation of tyrosine phosphorylases. Both effects activate signal transduction pathways leading either to apoptosis and/or to activation of tumor suppressor genes. Furthermore, vanadium compounds may induce cell-cycle arrest and/or cytotoxic effects through DNA cleavage and fragmentation and plasma membrane lipoperoxidation. Reactive oxygen species generated by Fenton-like reactions and/or during the intracellular reduction of V(V) to V(IV) by, mainly, NADPH, participate to the majority of the vanadium-induced intracellular events. Vanadium may also exert inhibitory effects on cancer cell metastatic potential through modulation of cellular adhesive molecules, and reverse antineoplastic drug resistance. It also possesses low toxicity that, in combination with the synthesis of new, more potent and better tolerated complexes, may establish vanadium as an effective non-platinum, metal antitumor agent.

The role of oxidative stress in mechanisms of metal-induced carcinogenesis.

Metals are necessary for the normal functioning of cells and the survival of organisms. However, exposure to higher than the physiological levels of several metals may lead to tumor development. Although the exact molecular mechanism(s) of metal-induced carcinogenesis is not clear, a vast body of evidence indicates that metal-induced generation of reactive oxygen species (ROS) may play a central role in this process. Two main pathways of ROS-induced effects are discussed in this chapter: (i) increased DNA damage induced either directly or indirectly by impeding DNA repair, and (ii) modulation of nuclear transcriptional factor activities, such as NF-kappaB and AP-1, through mitogen-activated protein kinases signal transduction mechanisms.