Formation Of Oxygen Free Radicals Research Articles

Biochemical effects of acute phoxim administration on antioxidant system and acetylcholinesterase in Oxya chinensis (Thunberg) (Orthoptera: Acrididae)

The study was undertaken to evaluate the effects of different concentrations of phoxim on acetylcholinesterase (AChE) and esterase (EST) activities, and antioxidant system after topical application to Oxya chinensis. The results showed that phoxim inhibited AChE activity, and did not cause significant changes in the EST activity and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). After phoxim administration, superoxide (SOD) and catalase (CAT) activities showed a biphasic response with an initial increase followed by a decline in their activities. Glutathione reductase (GR) and glutathione peroxidase (GPx) activities were inhibited in comparison with the control. Glutathione S-transferase (GST) activity showed irregular changes. Its activity increased significantly at the concentrations of 0.06 and 0.12 μg/μL and decreased at the concentrations of 0.09 and 0.24 μg/μL compared with the control. Changes in SOD, CAT, GST, GPx, and GR activities indicated that phoxim caused oxidative damage in O. chinensis. However, no significant changes in MDA content suggested that these enzymes played important roles in scavenging the oxidative free radicals induced by phoxim in O. chinensis. The formation of oxygen free radicals might be a factor in the toxicity of phoxim.

Baicalein Significantly Protects Human Retinal Pigment Epithelium Cells Against H2O2-Induced Oxidative Stress by Scavenging Reactive Oxygen Species and Downregulating the Expression of Matrix Metalloproteinase-9 and Vascular Endothelial Growth Factor

Age-related macular degeneration is a leading cause of blindness in the elderly. At a later stage, neovascular or exudative age-related macular degeneration can lead to severe central vision loss that is related to aging-associated cumulative oxidative stress of the human retinal pigment epithelium (hRPE) cells. Early prevention with antioxidants is mandatory. The aim of this study was to determine whether and how baicalein can act as an antioxidant. The methods used included lactate dehydrogenase, 2′,7′-dichloro-fluorescein diacetate, or enzyme-linked immunosorbent assay to measure cell viability, oxygen free radical levels, or the levels of vascular endothelial growth factor (VEGF)/matrix metalloproteinase-9 (MMP-9), respectively. H₂O₂ dose-dependently reduced the cell viability of hRPE cells. This negative effect was dose-dependently (with a lower effect at 20µM) and significantly counteracted by pretreatment with baicalein (50µM). Treatment with H₂O₂ significantly stimulated the formation of oxygen free radicals. This increase was dose-dependently and significantly blunted by baicalein. Further, treatment with a sublethal dose of H₂O₂ was associated with an upregulation in the levels of VEGF and MMP-9. The increases in these proteins were also dose-dependently (with a lower effect at 20µM) and significantly (50µM) blunted by pretreatment with baicalein. This study supports an antioxidative role for baicalein whereby it protects hRPE cells against H₂O₂-induced oxidative stress by downregulating the levels of VEGF and MMP-9, which are increased by H₂O₂.

Kardioprotektive Konditionierung

The extent of myocardial infarction depends primarily on the size of the perfusion territory of the occluded coronary artery, then on the duration of coronary occlusion and on collateral perfusion, and finally on the hemodynamic situation, notably heart rate. Early reperfusion is mandatory for salvage of ischemic myocardium; however, reperfusion is a double-edged sword and causally contributes to the extent of infarction through reperfusion injury. Short cycles of ischemia and reperfusion before (preconditioning) or following (postconditioning) a sustained coronary occlusion with reperfusion reduce infarct size. Pre- and postconditioning are also operative in the human heart. Such cardioprotection is effected by a complex signal transduction, initiated by extracellular triggers (autacoids, cytokines, growth factors), which activate an intracellular mediator cascade. Intracellular mediation requires activation of protein kinases. Mitochondria are central elements of signal mediation, notably by free oxygen radical formation, but also end-effectors which are decisive for cell death or survival. Age, comorbidities, and drugs interact with cardioprotection.

Effect of Celastrus paniculatus seed oil (Jyothismati oil) on acute and chronic immobilization stress induced in swiss albino mice

Stress alters the homeostasis and is produced by several factors. Immobilization stress induced due to reduced floor area provided for the mobility results in the imbalance of oxidant and antioxidant status. The modern computer savvy world decreases human mobility in the working environment, leading to the formation of oxygen free radicals and if left untreated might result in severe health problems like hypertension, cardiovascular disease, premature aging and brain dysfunction. Hence, modern medicines rely upon the medicinal plants for some drugs with zero side effects. In this context, Jyothismati oil (JO), extracted from Celastrus paniculatus seeds, was used to treat acute and chronic immobilization induced experimentally. C. paniculatus plant is considered to be rich in antioxidant content and so the seed oil extract's efficacy was tested against immobilization stress in albino mice. The animals were kept in a restrainer for short and long durations, grouped separately and fed with the drug. Animals were sacrificed and the samples were analyzed. The antioxidant enzyme levels of the animals regained and markedly increased in the acute and chronic immobilized groups, respectively. The results suggested that the extract of C. paniculatus seed was highly efficacious in reducing the stress induced by least mobility for hours.

Remission of Paroxysmal Atrial Fibrillation with Iron Reduction in Hemophilia A.

Abstract 5100Two male first cousins with mild hemophilia A had symptomatic electrocardiographically documented paroxysmal atrial fibrillation for several years that had become resistant to pharmacologic suppression. Both had baseline factor VIII levels of 12 to 15% and experienced bleeding requiring coagulation factor infusion therapy in response to trauma and surgical procedures. Radiofrequency ablation of ectopic electrical foci was considered in both cases but deferred because anticoagulation required to prevent thromboembolic complications of radiofrequency ablation carried an unacceptably high risk of bleeding. Iron accumulation with aging has been implicated in the pathogenesis of cardiovascular disease in general and arrhythmias in particular. Uncompensated iron-catalyzed oxygen free radical formation accounts for such toxicity. Remission of arrhythmias has been reported with iron reduction therapy in patients with iron overload disorders. Effects of iron reduction on arrhythmias in settings other than iron overload syndromes are unknown. Body iron stores as assessed by serum ferritin levels were elevated in both men (389 and 305 ng/ml respectively) but neither had the C282Y or H63D genes for hemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was performed and was followed by sustained remission of PAF in both cases. These findings suggest that iron reduction with maintenance of ferritin levels below about 100 ng/ml may be effective treatment for arrhythmias apart from the classic iron overload syndromes. Effects of primary prevention of iron accumulation over time and reduction of existing elevated iron stores deserve further study in patients with bleeding disorders in whom standard treatment of diseases of aging may be costly and carry high risk. The efficacy, safety, simplicity and cost effectiveness of iron reduction therapy commends application of this investigational approach to disease prevention and treatment in the general population. DisclosuresNo relevant conflicts of interest to declare.

Hyperbaric oxygen therapy as an anti-infective agent

Hyperbaric oxygen therapy (HBOT) involves inhalation of 100% oxygen at supra-atmospheric ambient pressure. HBOT is used as either a primary or adjunctive treatment in the management of infections such as gas gangrene, necrotizing fasciitis, diabetic foot infections, refractory osteomyelitis, neurosurgical infections and fungal infections. HBOT acts as a bactericidal/bacteriostatic agent against anerobic bacteria by increasing the formation of free oxygen radicals. HBOT restores the bacterial-killing capacity of leukocytes in hypoxic wounds by increasing tissue oxygen tensions. In addition, HBOT acts synergistically with a number of antibiotics. This article reviews the anti-infective effects of HBOT and the use of HBOT in the treatment of certain infectious diseases.

Differential regulation of the two rice ferritin genes ( OsFER1 and OsFER2)

Iron is essential to plants. However, when free and in excess, iron can catalyze the formation of oxygen free radicals. Ferritin, a protein capable of storing up to 4500 atoms of iron, can act as an iron buffer inside plant cells. Using a strategy based in amplicon size difference, we were able to analyze the expression profile of the two rice ferritin genes ( OsFER1 and OsFER2). Both genes are expressed, although with different regulation and organ distribution. Exposure to copper, Paraquat, SNP and excess iron led to accumulation of ferritin mRNA, remarkably of OsFER2. The iron-induced expression was abolished by treatment with GSH, indicating that the induction observed is dependent of an oxidative step. OsFER2 mRNA levels in rice flag leaves and panicles at different reproductive stages were higher than OsFER1 mRNA levels. No ferritin mRNA was detected in rice seeds. However, imbibition under light led to ferritin expression, which was abolished when seeds were kept in the dark, suggesting a light-regulated induction. Ferritin mRNA accumulation was seen in the dark only when seeds were germinated in the presence of externally supplied iron. We suggest that the primary role of rice ferritins is related to defense against iron-mediated oxidative stress.

Melatonin pretreatment attenuates diazinon-induced testicular damage in mice

Background: Diazinon is one of widely used organophosphrous pesticides, can affect both animals and man even after a single exposure. It has a dual toxicity due to acetylcholinestrase inhibition and formation of free oxygen radicals .So, the current work aimed to evaluate the effects of diazinon on the mice testes and the possible protective effect of melatonin. Material and Methods: Male CD-1 adult mice were divided into 6 groups, (1) control group,(2) melatonin group 10mg/kg,(3) diazinon group (30mg/kg), (4) diazinon group (60mg/kg),(5) diazinon 30mg + melatonin and (6) diazinon 60mg/kg + melatonin. Diazinon was orally administrated 1 and 28 days of treatment, whereas, melatonin was administrated intraperitoneally at a single dose. Testicular damage was examined by using hematoxyline and eosin staining. Results: Diazinon treated groups diminished the plasma acetylcholinestrase activity on day 1 of treatment. Morphometrical analysis showed a decrease in seminiferous thickness (day 1 and 28), with increased testicular superoxide dismutase (SOD) activity (day28). Melatonin pre-treatment prevented alterations induced by diazinon, except diminution of acetylcholinestrase activity. Conclusion: These results suggest that testicular damage observed post-treatment might be due to elevated concentration of free oxygen radicals (ROS) with diazinon while, pretreatment with a single dose of melatonin is a potentially beneficial agent to reduce testicular damage in adult mice probably by decreasing oxidative stress.

Melatonin pretreatment attenuates diazinon-induced testicular damage in mice

Background: Diazinon is one of widely used organophosphrous pesticides, can affect both animals and man even after a single exposure. It has a dual toxicity due to acetylcholinestrase inhibition and formation of free oxygen radicals .So, the current work aimed to evaluate the effects of diazinon on the mice testes and the possible protective effect of melatonin. Material and Methods: Male CD-1 adult mice were divided into 6 groups, (1) control group,(2) melatonin group 10mg/kg,(3) diazinon group (30mg/kg), (4) diazinon group (60mg/kg),(5) diazinon 30mg + melatonin and (6) diazinon 60mg/kg + melatonin. Diazinon was orally administrated 1 and 28 days of treatment, whereas, melatonin was administrated intraperitoneally at a single dose. Testicular damage was examined by using hematoxyline and eosin staining. Results: Diazinon treated groups diminished the plasma acetylcholinestrase activity on day 1 of treatment. Morphometrical analysis showed a decrease in seminiferous thickness (day 1 and 28), with increased testicular superoxide dismutase (SOD) activity (day28). Melatonin pre-treatment prevented alterations induced by diazinon, except diminution of acetylcholinestrase activity. Conclusion: These results suggest that testicular damage observed post-treatment might be due to elevated concentration of free oxygen radicals (ROS) with diazinon while, pretreatment with a single dose of melatonin is a potentially beneficial agent to reduce testicular damage in adult mice probably by decreasing oxidative stress.

Acute Renal Failure and Mechanical Ventilation: Reality or Myth?

Acute Renal Failure and Mechanical Ventilation: Reality or Myth?

Melatonin Prevents Cyclosporine-Induced Hepatotoxicity in Rats

Objectives: Cyclosporine A (CsA) is a widely used immunosuppressive agent that is implicated in the formation of free oxygen radicals. Melatonin is known to be a free radical scavenger and an antioxidant agent. This study was designed to investigate the effects of melatonin on CsA-induced liver damage by histopathological examination. Materials and Methods: Thirty-two male rats of Sprague-Dawley origin were divided into 4 groups of 8 and treated for 28 days as follows: group 1 received daily doses of 0.1 ml/kg olive oil s.c.; group 2 received 4 mg/kg of melatonin; group 3 received 10 mg/kg CsA diluted in 0.1 ml/kg olive oil; group 4 was treated with 4 mg/kg melatonin i.p. and 10 mg/kg CsA s.c. Finally, the rats were sacrificed by terminal anesthesia, and liver tissue specimens were processed for light microscopy, stained with HE and examined under a light microscope. Results: Specimens of the control group showed normal liver histology, whereas group 3 showed major histopathological changes, such as cytoplasmic vacuolization, dilatation of the sinusoids, apoptosis and many mitotic figures. In group 4, the normal histology of the liver was preserved, although apoptosis, mitotic figures and cytoplasmic vacuolization were still infrequently observed. Nevertheless, there were significant differences between group 2 (melatonin) and group 3 (CsA) and between group 3 (CsA) and group 4 (CsA + melatonin) concerning these 3 parameters (vacuolization, sinusoidal dilatation and apoptosis). Conclusion: The results of this study suggest that CsA-related liver toxicity in rats could be significantly reduced by melatonin administration.

Mecanismos básicos de lesión hepatocelular. Papel de los mediadores lipídicos de inflamación

The presence of a lesion in the cellular parenchyma is common to a large number of chronic liver diseases, such as viral hepatitides, alcoholic hepatitis, chronic cholestasis and steatohepatitis. Although the pathogenesis may vary according to the etiological agent, a series of mechanisms is common to all. Notable among these mechanisms are Kupffer cell activation and inflammatory cell recruitment, free oxygen radical formation and the development of oxidative stress, cytokine production, mainly TNFa and TGFb, and inflammatory mediator release due to arachidonic acid oxidation through the COX-2 and 5-LO pathways.

Attenuation of changes in capillary fine structure and leukocyte adhesion improves muscle performance following chronic ischaemia in rats

Acute ischaemia-reperfusion disrupts capillary fine structure and increases leukocyte adhesion in postcapillary venules. We determined whether chronic muscle ischaemia has similar consequences, and whether it is possible to ameliorate its effect on muscle performance. Following ischaemia (unilateral ligation, common iliac artery) rat hindlimb muscles were examined without other intervention or following treatment with an xanthine oxidase inhibitor (allopurinol), a Na(+)/H(+) exchange blocker (amiloride), or an oxygen free radical scavenger (vitamin E). No significant leukocyte adhesion or rolling, nor changes in capillary fine structure were observed 3 days postsurgery, when limb use was limited. However, leukocyte rolling and adhesion almost trebled by 7 days (P < 0.001), when normal gait was largely restored. Capillary fine structure was disturbed over a similar time course, e.g. relative endothelial volume (control 46%, 7 days 61%; P < 0.05), that resolved by 5 weeks. Where activity was increased by mild electrical stimulation 3 days after ligation muscles showed enhanced capillary swelling (endothelial volume 66% versus 50%, P < 0.005), but improved fatigue index (52% versus 16%, P < 0.001) as a result of greater blood flow. Muscle fatigue after ligation was related to the extent of contraction-induced hyperaemia (R(2) = 0.725), but not capillary swelling. Amiloride, and to a lesser extent allopurinol but not vitamin E, significantly decreased leukocyte rolling and adhesion, as well as capillary endothelial swelling. We conclude that increased activity of ischaemic muscles on recovery is likely to accentuate acidosis accompanying changes in microcirculation and contribute to enhanced muscle fatigue, whereas formation of oxygen free radicals may be attenuated by endogenous protective mechanisms.

Possible role of an ischemic preconditioning-like response mechanism in K ATP channel opener-mediated protection against streptozotocin-induced suppression of rat pancreatic islet function

Potassium channel openers (KCOs) decrease insulin secretion from β-cells. Some KCOs also protect against damage to β-cell function and type 1 diabetes in animal models. Previously we have found that the KCO NNC 55-0118 counteracted islet cell dysfunction, and this was associated with a lowering of the mitochondrial membrane potential (Δψ). Presently we aimed to explore whether inhibition of insulin secretion per se or rather inhibition of mitochondrial function correlates to counteraction of β-cell suppression. For this we used two novel KCOs (NNC 55-0321 and NNC 55-0462), which at certain concentrations have different actions regarding insulin secretion and the Δψ, with NNC 55-0321 being a potent inhibitor of Δψ and NNC 55-0462 being a potent inhibitor of insulin secretion. At 10 μM NNC 55-0321, but not with NNC 55-0462, the islet ATP content and ATP/ADP ratio was acutely decreased. This was accompanied by a complete protection against streptozotocin-induced suppression of islet insulin secretion using the former KCO. In cardiac research KCOs have been used to induce an ischemic preconditioning (IPC) response. In line with an IPC-like mechanism we found that NNC 55-0321 induced an initial free oxygen radical formation, PKC-ɛ isoform activation and a subsequent phosphorylation of the survival promoting factor Akt. Thus, KCOs may elicit mitochondrial events that resemble classical IPC seen in cardiomyocytes, and this could explain the enhanced islet cell function observed. KCOs with this property may be particularly interesting compounds to study as a rescue therapy during acute episodes of β-cell suppression/destruction.

Cardiac ischemia and reperfusion in spontaneously diabetic rats with and without application of EGb 761: I. cardiomyocytes.

Diabetic cardiomyopathy is known to result in increased mortality after ischemic events. Permanently increased oxidative stress with formation of oxygen-free radicals plays a key role in the development of specific heart muscle disease. Associated lesions include structural alterations to cardiomyocytes. Antioxidative treatment in addition to the usual insulin substitution would seem sensible in preventing or delaying long-term diabetic complications and protecting the myocardium against acute ischemic events. We investigated the effects of radical scavenger Ginkgo biloba extract EGb 761 against diabetes-induced damage to cardiomyocytes and additional ischemia/reperfusion injury in spontaneously diabetic BioBreeding/Ottawa Karlsburg (BB/OK) rats, as a model of diabetic myocardium infarction. Morphological and morphometric parameters of heart muscles were analyzed by light and electron-microscopic techniques. We used immunohistochemistry to evaluate parameters of oxidative stress (superoxide dismutase [SOD]) and inducible nitric oxide synthase (iNOS) protein expression. Our results indicated that A) Diabetic myocardium appears more vulnerable to ischemia/reperfusion damage concerning ultrastructure of cardiomyocytes (sarcomeres, vacuoles, mitochondria), expression of antioxidative enzymes (CuZnSOD, MnSOD), and iNOS than normal myocardium; B) Pre-treatment of diabetic myocardium with EGb and additional ischemia/reperfusion leads to a relative improvement in myocardial ultrastructure compared to unprotected myocardium. In summary, EGb appears to be promising as an adjuvant therapeutic drug in diabetics with respect to ischemic myocardium injury. It may contribute to the prevention of late diabetic complications in diabetic cardiomyopathy.

Protective effects of vitamin E and omeprazole on the hypoxia/reoxygenation induced intestinal injury in newborn rats

Evaluation of prophylactic effects of omeprazole and/or vitamin E on the formation of free oxygen radicals (FOR) and bowel histopathology in the newborn rat model of hypoxia/reoxygenation (H/R) that resembles human necrotizing enterocolitis (NEC). Eighty newborn rats were randomly divided into eight groups. H/R was done using airtight chamber. Rats were exposed to 100% CO2 for 15 min followed by a reoxygenation for the next 15 min with 100% O2. Group 1 (n = 10) was the control group. Group 2 (n = 10) rats received vitamin E. In Group 3 (n = 10) omeprazole was administrated. Group 4 (n = 10) rats received omeprazole and vitamin E. Group 5 (n = 10) rats were subjected to H/R two times for 2 days and one time for 3 days. Group 6 (n = 10) received vitamin E in addition to H/R for 5 days and in Group 7 (n = 10) omeprazole in addition to H/R for 5 days. In Group 8 (n = 10), vitamin E and omeprazole and H/R were applied for 5 days. Rats were killed at the end of the each process and bowel specimens were harvested for histopathological and biochemical investigations. We administrated vitamin E intramuscularly 300 unit/kg per day and omeprazole orally 20 mg/kg per day. Malondialdehyde (MDA), xanthine oxidase (XO), xanthine dehydogenase (XDH) and XO/(XO + XDH) were measured. Vitamin E and/or omeprazole treated rats had significantly less XO% levels than H/R only group (0.36, 0.38 and 0.57, respectively). Similarly, the MDA levels were significantly lower in vitamin E and/or omeprazole received rats than H/R only rats (88.8, 97.9 and 122.6, respectively). All rats treated with omeprazole and/or vitamin E had better biochemical and histopathological levels compared to H/R rats (p < 0.05). Histopathological results show that Group 5 (H/R only) had significantly more intestinal damage when compared with Group 6 (vitamin E + H/R), Group 7 (omeprazole + R/H) and Group 8 (vitamin E + omeprazole + H/R) (p < 0.001). Grade 2 and 3 intestinal damages were only in Group 5 and there were no statistical difference between in Groups 6, 7 and 8 (p > 0.001). Omeprazole and/or vitamin E may protect the biochemical and histopathological intestinal damage of H/R injury in rats. These drugs may be beneficial in the prophylaxis of NEC in humans as well.

JunD Protects the Liver from Ischemia/Reperfusion Injury by Dampening AP-1 Transcriptional Activation

The AP-1 transcription factor modulates a wide range of cellular processes, including cellular proliferation, programmed cell death, and survival. JunD is a major component of the AP-1 complex following liver ischemia/reperfusion (I/R) injury; however, its precise function in this setting remains unclear. We investigated the functional significance of JunD in regulating AP-1 transcription following partial lobar I/R injury to the liver, as well as the downstream consequences for hepatocellular remodeling. Our findings demonstrate that JunD plays a protective role, reducing I/R injury to the liver by suppressing acute transcriptional activation of AP-1. In the absence of JunD, c-Jun phosphorylation and AP-1 activation in response to I/R injury were elevated, and this correlated with increased caspase activation, injury, and alterations in hepatocyte proliferation. The expression of dominant negative JNK1 inhibited c-Jun phosphorylation, AP-1 activation, and hepatic injury following I/R in JunD-/- mice but, paradoxically, led to an enhancement of AP-1 activation and liver injury in JunD+/- littermates. Enhanced JunD/JNK1-dependent liver injury correlated with the acute induction of diphenylene iodonium-sensitive NADPH-dependent superoxide production by the liver following I/R. In this context, dominant negative JNK1 expression elevated both Nox2 and Nox4 mRNA levels in the liver in a JunD-dependent manner. These findings suggest that JunD counterbalances JNK1 activation and the downstream redox-dependent hepatic injury that results from I/R, and may do so by regulating NADPH oxidases.

Carbon monoxide inhibits myocardial oxygen free radical generation following the onset of ischemia

Reperfusion of the ischemic heart causes a burst of oxygen free radical (OFR) formation and secondary myocardial damage. However, questions remain on the mechanisms of OFR generation during ischemia. Recently, it has been reported that superoxide can derive from heme‐protein oxidation immediately following the onset of ischemia. Therefore, we tested the hypothesis that if OFR generation following ischemia involves heme‐protein oxidation then it should be inhibited by carbon monoxide (CO). Surface fluorometry was used to measure OFR generation during the onset of global ischemia in isolated rat heart. The fiber optic probe facing the left ventricle (LV) obtained the fluorescence signal from the heart. Hydroethidine (HE) was used as a sensitive probe to measure superoxide. When exposed to superoxide, HE is converted to ethidium (ET). Hearts were perfused with 44μM HE for 1.5 −5 min. We observed a rapid increase in ET signal with the onset of ischemia and that reached to a peak within 5 min. ET signal was completed blocked by a SOD mimic, MnPyP (250μM, P&lt;0.01). Importantly, CO (100μM) treatment significantly reduced ET signal to 30% of control (P&lt;0.01). Thus, there is a burst of OFR generation during the onset of myocardial ischemia in isolated rat heart. We report for the first time that CO inhibits OFR generation during myocardial ischemia, indicating that heme‐protein oxidation plays a crucial role in OFR generation.

OXIDATIVE STATUS IN HEAVY SMOKERS: EFFECT OF NUTRITION SUPPLEMENTS

Long‐term cigarette smoking can cause oxygen free radical (ROS) formation and antioxidant capacity depletion, leading to oxidative stress involved in many disorders. Active ROS produces lipid peroxidation generating molecules such as oxidized LDL (oxLDL) and malondialdehyde (MDA) used as indexes of oxidative damage.An adequate diet and/or supplementation may attenuate this condition.To evaluate potential beneficial effects of supplementation with two different encapsulated formulas, consisting primarily of mixed juice powder concentrate, a placebo‐controlled double‐blind study was performed on 61 heavy smokers (&gt;20 cigarettes/d, duration ≥10y, age 40–60y, 35 male). Subjects were randomized into 3 groups: A‐placebo; B‐fruit/vegetable; and, C‐fruit/vegetable/berry. We measured serum oxLDL and plasma free MDA (f‐MDA), the chemically active form, index of recent damage.Values (mean±SD) were compared at baseline (T0) and after 3 months supplementation (T1).Nutritional supplementation produced a decrease in oxidative damage indexes, more evident in group C than B, and seems to attenuate smoking effects.Support: NSA, Collierville, TN

Effects of proteasome inhibitor, MG132, on proteasome activity and oxidative status of rat liver

In vivo effects of N-benzyloxycarbonyl (Cbz)-Leu-Leu-leucinal (MG132) on chymotryptic-like (ChT-L), tryptic-like, and post-glutamyl peptide hydrolytic-like proteasome activities, protein oxidation, lipid peroxidation (LP), glutathione (GSH) level, as well as on the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-reductase) in the rat liver were studied. The possibility of MG132 provoking the formation of free oxygen radicals was also assayed in primary hepatocytes. The following results were obtained: (1) In vivo, MG132 did not change the spontaneous LP, but increased Fe-induced LP and the amount of oxidized proteins; it decreased the GSH level in liver. From the proteasome activities studied in liver cytosol only ChT-L activity was significantly decreased after MG132 administration. Furthermore, MG132 increased antioxidant enzyme activities of SOD, CAT, and GSH-Px. (2) In vitro, MG132 increased free radical oxygen species in hepatocytes; this effect disappeared in the presence of CAT or mannitol. In conclusion, since nowadays proteasome inhibitors are entering into the swing of laboratory and clinical practice, the present data could provide useful information for MG132 action. Consequently, future in vivo experiments with MG132 could highlight the possibility of its use at different pathological conditions.