Role Of Free Radicals Research Articles

Superoxide dismutase and glutathione peroxidase enzyme activities in larynx carcinoma

Conclusions. It can be concluded that these changes are related to damage at the DNA level or to the inhibitory effects of tumor promoters. Increases in GSH-Px activities may be related to the independence of this enzyme from the suppressive effects of tumor promoters. This study and others in the literature show that it is not possible to generalize the activities of SOD and GSH-Px in cancer. Objective. There has been growing interest in the role of free radicals as a cause of cancer. It has been suggested that an increase in activated forms of oxygen in cells due to overproduction and/or the inability to destroy them may lead to severe damage of cell structures. As a result of these changes, some chromosomal aberrations and carcinogenesis may develop. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are two important antioxidant enzymes involved in enzymatic antioxidant defense mechanisms. To our knowledge there have been no previous studies in the literature investigating the activities of SOD and GSH-Px in laryngeal cancer. Material and methods. The study subjects comprised 10 male patients (age range 43–76 years) with laryngeal carcinoma and 10 healthy controls (4 males, 6 females; age range 40–69 years) with intraoral hyperplastic fibrous tissue. Homogenate SOD and GSH-Px activities were measured using commercially available kits. Results. GSH-Px levels were significantly increased in the cancerous tissues compared with cancer-free adjacent tissues and fibrous hyperplasia tissues (p<0.05), whereas there was no significant difference between SOD activities (p>0.05). There was also no significant difference between GSH-Px activity in cancer-free adjacent tissues and fibrous hyperplasia tissues (p>0.05).

Roles of Free Radicals, Nitric Oxide, and Scavenging Enzymes in Nasal Polyp Development

The aim of this study was to investigate the role of nitric oxide (NO), free oxygen radicals, and scavenging enzymes in the development of nasal polyp (NP) disease. This study included 41 patients who underwent endoscopic surgery because of NPs. Control specimens were taken from the inferior turbinate of 32 patients who underwent septoplasty. The levels of malondialdehyde (MDA), NO, and superoxide dismutase (SOD) were measured in intraoperative specimens of polyp tissue and turbinate mucosa. The levels of tissue NO were 191.06 +/- 26.62 micromol/mg of protein in patients with NPs and 145.30 +/- 19.19 micromol/mg of protein (p < .001) in the control group. The levels of MDA in the study and control groups were 12.47 +/- 2.12 nmol/mg and 8.83 +/- 1.08 nmol/mg (p < .01), respectively. The levels of SOD in the study and control groups were 50.77 +/- 14.74 U/mg and 77.93 +/- 15.31 U/mg (p < .001), respectively. It was determined that the levels of MDA in plasma and erythrocytes were higher in the patients with NPs than in the control group (p < .05). The levels of NO in plasma and erythrocytes in both groups were similar. The levels of SOD in plasma and erythrocytes were lower in patients with NPs than in the control group (p > .05). Increases in the levels of tissue MDA and NO and decreases in scavenging enzymes in patients with NPs as compared to control groups may indicate the presence of free radical damage in patients with nasal NPs. New studies are needed to clarify the efficacy of using antioxidants in the treatment of NPs.

Poly(ADP-ribose) polymerase inhibition attenuates biventricular reperfusion injury after orthotopic heart transplantation☆

Poly (ADP-ribose) polymerase (PARP) activation plays a key role in free radical induced injury in ischemia/reperfusion. We investigated the effects of INO-1001 a novel PARP inhibitor on postischemic myocardial and endothelial function. In dogs, 12 orthotopic heart transplantations were performed after 4 h ischemic preservation. At the beginning of reperfusion either saline vehicle (control, n=6), or INO-1001 (1 mg/kg, n=6) was applied. Before explantation and after 120 min of reperfusion we measured biventricular pressure-volume relationships by a combined conductance catheter and the adaptation potential of the right ventricle to acute afterload increase by pulmonary banding. Coronary blood flow (CBF), vasoreactivity, PARP-activation and ATP-content were also determined. INO-1001 led to significantly better recovery of contractility (91+/-3 vs. 44+/-7%, P<0.05) and CBF (44+/-4 vs. 29+/-3 ml/min, P<0.05) and higher increase in CBF after acetylcholine (61+/-10 vs. 27+/-8%, P<0.05). In addition, the inotropic adaptation potential of the right ventricle to an increased afterload was better preserved after INO-1001. ATP content was significantly higher in the INO-1001 group (11.0+/-2.1 vs. 4.5+/-1.1 micromol/g drw). Immunohistology revealed PARP activation in the control group which was abolished by INO-1001 treatment. PARP inhibition reduces myocardial and endothelial reperfusion injury after orthotopic heart transplantation.

Evaluation of Oxidative Stress in Cutaneous Leishmaniasis

Oxidative stress occurs when there is excessive free-radical production or a low antioxidant level. The role of free radicals in the pathogenesis and in the progression of many diseases has often been discussed, but it has not been widely investigated in leishmaniasis. However, measurement of oxidants and antioxidants in the serum seems to be of great value. In this study, we aimed to determine lipid peroxidation levels as markers of oxidative stress in the serum of patients suffering from cutaneous leishmaniasis, which is a common health problem in our region of Southern Anatolia, Turkey. Forty patients aged between 5-50 years and forty controls aged between 5-50 years were included in the study. The LPO levels of the patients with active cutaneous leishmaniasis were significantly higher (p<0.001) than those of healthy controls. As a result, it is possible to conclude that patients with cutaneous leishmaniasis are affected by oxidative stress, which may contribute to the progression of the disease.

Anesthetic Preconditioning: The Role of Free Radicals in Sevoflurane-Induced Attenuation of Mitochondrial Electron Transport in Guinea Pig Isolated Hearts

Cardioprotection by anesthetic preconditioning (APC) can be abolished by nitric oxide (NO*) synthase inhibitors or by reactive oxygen species (ROS) scavengers. We previously reported attenuated mitochondrial electron transport (ET) and increased ROS generation during preconditioning sevoflurane exposure as part of the triggering mechanism of APC. We hypothesized that NO* and other ROS mediate anesthetic-induced ET attenuation. Cardiac function and reduced nicotinamide adenine dinucleotide (NADH) fluorescence, an index of mitochondrial ET, were measured online in 68 Langendorff-prepared guinea pig hearts. Hearts underwent 30 min of global ischemia and 120 min of reperfusion. Before ischemia, hearts were temporarily perfused with superoxide dismutase, catalase, and glutathione to scavenge ROS or N(G)-nitro-L-arginine-methyl-ester (L-NAME) to inhibit NO* synthase in the presence or absence of 1.3 mM sevoflurane (APC). APC temporarily increased NADH before ischemia, i.e., it attenuated mitochondrial ET. Both this NADH increase and the cardioprotection by APC on reperfusion were prevented by superoxide dismutase, catalase, and glutathione and by N(G)-nitro-L-arginine-methyl-ester. Thus, ROS and NO*, or reaction products including peroxynitrite, mediate sevoflurane-induced ET attenuation. This may lead to a positive feedback mechanism with augmented ROS generation to trigger APC secondary to altered mitochondrial function.

Plasma Values of Oxidants and Antioxidants in Acute Brain Hemorrhage: Role of Free Radicals in the Development of Brain Injury

The levels of oxidants xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GRD) were determined in plasma within 24 h after onset of hemorrhagic stroke in 17 patients (9 men and 8 women, aged 60.7+/-11.5 yr) and in 20 healthy controls (12 men and 8 women, aged 62.5+/-8.3 yr). Compared to controls, the plasma SOD and total superoxide scavenger activities (TSSA) were significantly lower and the NO levels were significantly higher among the stroke patients. XO showed a slight, nonsignificant increase in the patients, but the levels of MDA, NSSA, GRD, and GSH-Px did not show any significant differences between the two groups. The hemorrhage volume was negatively correlated with the initial score of the Glasgow Coma Scale and a positive correlation with lethal outcome, but it did not correlate significantly with any of the measured parameters. The results suggest that free radicals might play a role in the development of brain injury following brain hemorrhage.

Free radicals trigger TNF?-induced cardioprotection

Tumor Necrosis Factor alpha (TNF alpha) induces programmed cell death and contributes to cardiac ischemia/reperfusion injury. Paradoxically, we have recently demonstrated that low doses of TNF alpha can induce cardiac preconditioning (PC). We hypothesized that the production of free radicals participates in this cardioprotective program. Control isolated rat hearts underwent 30 min regional ischemia and 120 min of reperfusion. A second group of hearts received a low dose of TNF alpha (0.5 ng/ml) for 7 min followed by 10 min washout prior to I/R. In other groups, the antioxidant N-2-mercaptopropionyl glycine (MPG) (1 mM) was given for 15 min prior to I/R alone or during TNF alpha perfusion. Infarct size was determined at the end of the reperfusion period. Ventricular catalase and superoxide dismutase activities were assessed as an index of oxidative stress and free radical production was directly measured by the oxidation of 1-hydroxy-3-carboxy-pyrrolidine (CP-H) to paramagnetic 3-carboxy-proxyl (CP.) using electron spin resonance spectroscopy. TNF alpha reduced the infarct/area at risk (I/AAR) ratio (7.2+/-1.7% vs. 36.5+/-1.7% for controls, p<0.05). MPG reduced the cardioprotective effect of TNF alpha (I/AAR ratio: 20.5+/-3.3%, p<0.05). TNF alpha-perfusion increased catalase activity in the ventricles (15.8+/-1.2 I.U./mg for controls vs. 19.9+/-1.1 I.U/mg for TNF alpha, p<0.05). Proof of formation of free radicals was increased CP formation in the coronary effluent during TNF alpha infusion (24.2+/-4.5 for TNF alpha vs. 11.9+/-1.5 arbitrary units for controls, p<0.05), with decreased CP after addition of MPG. Our data provide firm evidence for a production and role of free radicals in TNF alpha-induced cardioprotection.

RETRACTED: Prospects for the future: the role of free radicals in the treatment of stroke

This article has been retracted at the request of the Editor-in-Chief.Reason: it plagiarises parts of a previously published paper: “Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia”, by Carolina M. Maier et al., Neurobiology of Disease (2002), Vol 11, Issue 1, 28–42.

The role of free radicals in the reaction of dimethyldioxirane with adamantane

The role of free radicals in the reaction of dimethyldioxirane with adamantane

Oxidants and antioxidants in hypoxic ischaemic encephalopathy.

In the present study, the role of serum lipid peroxide and serum nitric oxide as oxidants and erythrocytic superoxide dismutase & serum vitamin E as antioxidants were determined in the 50 neonates with hypoxic ischaemic encephalopathy. (HIE) as against 25 healthy neonates as controls 50 patients of HIE were further divided into two groups i. e. mild and moderate HIE patients. All subjects were in the age group of 37-41 weeks of gestation. The levels of serum lipid peroxide, serum nitric oxide and erythrocytic superoxide dismutase were significantly elevated in both groups of neonates with HIE than those of controls (P<0.001), whereas serum vitamin E levels were significantly decreased in both groups of HIE patients than those of controls (P<0.001). A positive correlation was obtained between serum lipid peroxide and erythrocytic superoxide dismutase (r=+0.86). Alterations in the status of oxidants and antioxidants indicate role of free radicals in the development of HIE.

Myocardial injury and its prevention in the perioperative setting

Myocardial injury and its prevention in the perioperative setting

Oxidative stress in mild cognitive impairment and Alzheimer disease: a continuum.

Although several studies show the importance of oxidative stress in the pathogenesis of Alzheimer's disease (AD), there are few evidences on the role of free radicals in Mild Cognitive Impairment (MCI). Our results showing a marked decrease of the main components of the antioxidant defense system of the organism support the hypothesis that in MCI there is a condition of oxidative stress. This work also gives an overview on the existing evidence of the early occurrence of oxidative processes in the development of dementing disorders of the Alzheimer type. Since MCI represents a condition of increased risk for AD, use of antioxidants in MCI could be of importance for prevention.

Mode of action of endotoxin: role of free radicals and antioxidants.

The pathogenetic sequence of reactions mediated by endotoxin (LPS) leading to the production of sepsis involves the oxygen radicals or reactive oxygen species, which has been evaluated in the present review. Among reactive oxygen species hydroxyl radical either singly or in combination with peroxynitrite, produces tissue damage often observed during septic injury. Inactivation of these damaging radicals by antioxidants or nitric oxide inhibitor(s) may be helpful for protecting sepsis mediated derangements but the application of these agents as drugs in humans has not been fully successful. Transcription factor NF-kappa B is reported to be the oxygen sensor in LPS induced endotoxemia. Polyphenols, especially the catechin group of compounds, are important therapeutic agents, which may be used for the treatment of endotoxin mediated sepsis.

INO-1001, a novel poly(ADP-ribose) polymerase inhibitor reduces myocardial and endothelial reperfusion injury after orthotopic heart transplantation

Poly (ADP-ribose) polymerase (PARP) activation plays a key role in free radical induced injury in the context of ischemia/reperfusion. In the present study, we investigated the effects of INO-1001 a novel ultrapotent PARP inhibitor on postischemic myocardial and endothelial function in a canine heart transplantation model. After 4 hours of ischemic preservation, 12 orthotopic heart transplantations were performed. At the beginning of reperfusion either saline vehicle (control, n = 6), or INO-1001 (1 mg/kg, n = 6) was applied. Left ventricular pressure-volume relationships were measured by a combined pressure-conductance catheter and the slope of the end-systolic pressure volume relationship (Ees) was calculated as a load-independent index of myocardial contractility before explantation and after 120 minutes of reperfusion. Coronary blood flow (CBF), endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) were also determined. Serial biopsies were taken to determine ATP-content and for immunhistology. Admimistration of INO-1001 led to significantly better recovery (given as percent of baseline) of Ees (91 ± 3 vs. 44 ± 7 %, p < 0.05). CBF was significantly higher in the INO-1001 group (44 ± 4 vs. 29 ± 3, ml/min, p < 0.05). While the vasodilatatory response to SNP was similar in both groups, ACH resulted in a significantly higher increase in CBF in the INO-1001 group (61 ± 10% vs. 27 ± 8%, p < 0.05). ATP content was significantly higher in the in the INO-1001 group (11.0 ± 2.1 vs. 4.5 ± 1.1 μmol/g drw). Immunhistology revealed PARP activation in the control group which was abolished by INO-1001 treatment. Thus, PARP inhibition reduces myocardial and endothelial reperfusion injury after orthotopic heart transplantation.

2 Advances in organic chemistry over the last 100 years

This chapter attempts to cover the last century of organic chemistry, inevitably in an impressionistic way. It highlights the most important developments relating to structure and its determination, stereochemistry, synthesis, new types of molecule that do not occur in nature, a limited selection of natural products, the rise of theoretical organic chemistry and the role of free radicals. The discussion opens with a state-of-the-art picture for 1904 (when Annual Reports made its first appearance) and concludes with some reflections on the position today, particularly in relation to the place of organic chemistry within science as a whole.

Brief Clinical Study: LIPID PEROXIDATION AND ANTIOXIDANT STATUS IN CHILDREN WITH ACUTE PURULENT MENINGITIS AND ENCEPHALITIS

In this study, lipid peroxidation and antioxidant status were investigated in children with acute bacterial meningitis and encephalitis. The aim was to determine whether there was a possible role of free radicals in meningitis and encephalitis in childhood. Our study included 16 children with acute bacterial meningitis, 13 with encephalitis, and 17 control subjects. Serum malondialdehyde (MDA), reduced glutathione (GSH), vitamin C, vitamin E, beta-carotene, and retinol levels were studied in all subjects within 6 h of admission. There was a statistically significant difference for serum MDA, GSH, and vitamin C between the groups. Serum MDA and vitamin C levels were higher, and serum GSH levels were lower in the study groups compared to the control group. Vitamin C levels were similar in both the encephalitis and control groups, but they were significantly lower in the children with encephalitis than the meningitis group. In conclusion, our study showed that serum MDA and GSH levels were affected in children with both meningitis and encephalitis, but vitamin C level was affected only in children with meningitis. Serum vitamin E, beta-carotene, and retinol levels were not changed in childhood meningitis and encephalitis

Avaliação da produção de espécies reativas de oxigênio por granulócitos de sangue periférico de pacientes com fibromialgia primária

OBJETIVO: avaliar anormalidades bioquimicas que possam estar relacionadas a fibromialgia, mais especificamente o metabolismo oxidante de granulocitos de pacientes com fibromialgia primaria (FMP). METODOS: foram selecionados 10 pacientes (9 mulheres e 1 homem) portadores de FMP, com idade entre 20 e 40 anos, de acordo com os criterios do Colegio Americano de Reumatologia, que nao apresentavam qualquer outra doenca de curso agudo ou cronico e estavam sem utilizar medicamentos no minimo durante duas semanas. Controles normais (n = 19) pareados por sexo e idade foram selecionados. Os granulocitos de pacientes e controles foram separados do sangue periferico e utilizados como celula de trabalho. A producao de especies reativas de oxigenio (ERO) foi determinada por meio de ensaio de quimioluminescencia dependente de luminol. RESULTADOS: demonstramos, pela primeira vez, uma producao significantemente elevada de ERO (3,2 vezes maior) em granulocitos de sangue periferico de pacientes com FMP (p < 0,05). CONCLUSOES: estes resultados demonstraram um comportamento anormal dos granulocitos de pacientes com FMP, em que uma producao aumentada de especies reativas do oxigenio foi observada. Estudos futuros serao necessarios para melhor esclarecer estes resultados, delineando uma nova perspectiva na compreensao e abordagem destes pacientes.

The role of free radicals in the muscle vasodilatation of systemic hypoxia in the rat.

Muscle vasodilatation evoked by systemic hypoxia is adenosine mediated and nitric oxide (NO) dependent: recent evidence suggests the increased binding of NO at complex IV of endothelial mitochondria when O(2) level falls leads to adenosine release. In this study on anaesthetised rats, the increase in femoral vascular conductance (FVC) evoked by systemic hypoxia (breathing 8 % O(2) for 5 min) was reduced by oxypurinol which inhibits xanthine oxidase (XO): XO generates O(2)(-) from hypoxanthine, a metabolite of adenosine. By contrast, infusion of superoxide dismutase (SOD), which dismutes O(2)(-) to hydrogen peroxide (H(2)O(2)), potentiated the hypoxia-evoked increase in FVC. However, NO synthesis inhibition reduced the hypoxia-evoked increase in FVC and it was not further altered by SOD. In other studies, the spinotrapezius muscle was pre-loaded with hydroethidine (HE), or dihydrorhodamine (DHR) which fluoresce in the presence of O(2)(-) and H(2)O(2), respectively. In muscle loaded with HE, systemic hypoxia increased fluorescence in endothelial cells of arterioles, whereas in muscle loaded with DHR, fluorescence was diffusely located in and around arteriolar endothelium. We propose that in systemic hypoxia, O(2)(-) generated by the XO degradation pathway from adenosine released by endothelial cells, and released by endothelial mitochondria by increased binding of NO to complex IV, is dismuted to H(2)O(2), which facilitates hypoxia-induced dilatation.

Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome

The role of free radicals and reactive oxygen species (ROS) in female reproductive function is still unclear. The present study was designed to investigate their relationship with ovulation, fertilization and conception. Follicular aspirates obtained from women undergoing IVF following controlled ovarian stimulation were evaluated using the ferric reducing antioxidant power (FRAP) assay for baseline total antioxidant capacity (TAC). Both the baseline TAC and the decline in TAC over 72 h (two-point assay) were used as markers of oxygen radical activity. A total of 303 follicular aspirates from 63 women were analysed. Two hundred and eighteen (71.9%) yielded oocytes, 169 (77.5%) of these fertilized and 134 (79.3%) of these embryos survived until the time of embryo transfer. Baseline TAC was no different in follicular fluid whether the follicle contained an oocyte or not, but was significantly higher in fluid from follicles whose oocyte successfully fertilized and significantly lower in fluid from follicles where the resultant embryo survived to transfer. The decline in TAC was lower when the oocytes fertilized and higher in association with embryo viability, but the differences were not statistically significant. These results provide further evidence that ROS play a role in female reproductive function.

Effect of Short-Term and Long-Term Antioxidant Therapy on Primary and Secondary Ageing Neurovascular Processes

Previous studies from our laboratory demonstrated an age-related functional decline in sensory neurones and their modulation of microvascular blood flow (primary ageing processes) that correlated with a deficiency in tissue repair (a secondary ageing process). We also raised the notion of a possible role for free radicals in these age-related changes. The aim of this study was to investigate the impact of antioxidant therapy on modulating sensory neurovascular function and tissue repair with age. Twenty-four-month-old Sprague-Dawley rats were treated with vitamin E for short-term (40 mg/kg, i.p., every other day for 2 weeks) or long-term (for 12 months in advance, 10 g/kg, incorporated in food). These treated rats were assessed for the effectiveness of treatment and tested for their sensory neurovascular function, repair of full-thickness burn, and recovery from hyperalgesia following nerve injury. The results indicate that both short- and long-term vitamin E treatments are effective in improving sensory neurovascular function and in reducing the time required for complete wound closure of full-thickness burn injury. Short-term vitamin E treatment was more effective in protecting against the development of hyperalgesia following nerve injury. An initial increase in wound size and in hyperalgesia was observed in the treated animals, and could reflect possible side effects of the antioxidant therapy and support the importance of free radicals in early stages of the repair process. The data, overall, support the notion that oxidative damage contributes to both primary and secondary ageing processes.