Free Radical-mediated Injury Research Articles

High-dose atorvastatin reduces oxidative stress of ischemia/reperfusion injury after isogeneic kidney transplantation in rats: in vivo, preclinical, case–control, open-label study

BackgroundRenal ischemia/reperfusion injury is an unavoidable event in transplantation in which free radical-mediated injury determines release of pro-inflammatory cytokines and activation of innate immunity. In addition to their cholesterol-lowering action, statins have shown dose-dependent pleiotropic effects on inflammatory pathways and oxidative stress. We investigated the effects of high-dose atorvastatin (atorvastatin 40 mg/kg) in preventing ischemia/reperfusion injury in an animal model of kidney transplant.MethodsForty female rats underwent left nephrectomy and orthotopic autotransplantation. Animals were divided in four groups: A = Transplant only; B = high-dose atorvastatin + Transplant; C = right nephrectomy + Transplant; D = high-dose atorvastatin + right nephrectomy + Transplant. Bilateral nephrectomy was performed 24 h post-transplant. Oxidative stress was assessed measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activity on renal tissue; ischemia/reperfusion injury was also evaluated by histology. Donor pre-treatment with high-dose atorvastatin improved oxidative stress.ResultsMDA levels were lower in group B versus A (p = 0.002) and D (p = 0.004). High-dose atorvastatin pre-treated rats displayed higher GPx activity in group B versus A (p = 0.009) and D (p = 0.005). SOD scavenger activity was also higher in group B versus A (p < 0.001) D (p < 0.001) and C (p = 0.003). MPO activity was lower in group B versus A (p = 0.02), C (p = 0.007) and D (p = 0.03). Histology revealed significantly lower rate of intratubular casts and luminal congestion in Group D versus C (p = 0.02 and p = 0.008, respectively).ConclusionsHigh-dose atorvastatin pre-treatment reduces oxidative stress and inflammation in a model of kidney transplant in the rat.

Dietary Magnesium Deficiency in Rats Enhances Free Radical Production in Skeletal Muscle

Recent studies suggest that free radicals may be involved in tissue injuries induced by magnesium deficiency. The aim of the present study was to assess the effect of magnesium deficiency on free radical production of skeletal muscle tissue. Male Wistar rats were pair-fed from weaning for 12 d either control or Mg-deficient diets containing 960 or 40 mg magnesium/kg diet, respectively. In the Mg-deficient rats, hypomagnesemia was accompanied by significantly lower magnesium and greater calcium concentrations in skeletal muscle tissue. Electron microscopy of skeletal muscle tissue revealed ultrastructural changes, including swelling mitochondria and disorganization of the sar-coplasmic reticulum network. Using the spin-trapping technique, we showed that significantly more hydroxyl radicals were generated in muscle homogenates of Mg-deficient rats. Moreover, the amount of spin trap adducts was increased in the presence of exogenous iron in both groups. In agreement with these observations, a greater concentration of thiobarbituric acid-reactive substances and a lower concentration of thiol groups were found in skeletal muscle of the Mg-deficient group compared with controls. These results strongly support the hypothesis that free radical-mediated injury could contribute to skeletal muscle lesions resulting from magnesium deficiency.

An In vitro Evaluation of Potential Free Radical Scavenging Antioxidant activity of selected Novel Synthetic Flavones

Background: The study of free radicals nowadays have become more attention as these are evoked continuously due to hazardous environmental conditions and food habits. Endogenously free radicals are introduced in our body due to exposure to different physiochemical conditions or some pathological states by various mechanisms. Oxidative stress occurs due to exposure of excess free radicals to body. Antioxidants act as a major defence against the free radical-mediated injury by scavenging them. Majority of the flavonoids found in plant products are known as antioxidants as they selectively scavenge the free radicals. Methods: Synthetic flavones (VMF41, VMF 43, VMF 45 and VMF 46) having different side chains on the: 3-hydroxy-2- (5-methyl, 7-methyl, 6-methyl, and 7--methoxy) 2- thiophen-4H-chromen-4-one structure were examined for free radical scavenging potential over nitric oxide, hydroxyl, and superoxide anion radicals by using appropriate in-vitro assay methods. Results and Discussion: Overall, with few exceptions, all the synthetic flavonoids (SFs) exhibited moderate free radical scavenging activity as compared to the standard drug. The test samples in the study showed dose dependant activity of scavenging activity. In nitric oxide radial scavenging activity, test flavonoids VMF 45 and VMF 46 exhibited significant scavenging activity at 50- 100µg/ml concentrations. The SFs VMF 43 and VMF 46 showed a good scavenging activity for hydroxyl, nitric oxide radicals and compounds VMF41, and VMF 43 showed significant scavenging activity at 50 µg/ml to 100µg/ml concentrations for superoxide radicals. However all the SFs at 10µg/ml concentration showed the low or poor radical scavenging activity. Conclusion: It is clear that these synthetic flavonoids (SFs) can be considered as potential antioxidant agents, however needs to be further tested at in vivo experiment to consider them as a lead antioxidant drug candidates.

Glutathione improves the prognosis of Intrauterine Growth Restriction via downregulated hepatic and renal TNFα expression in Wistar rats

Objective: Oxidative stress is requisite for the development of IUGR, with subsequent manifestation in the reduced levels of antioxidants enzymes. Glutathione protects against free radical-mediated injury, therefore we elucidated on its role in protecting against oxidative stress-induced consequences of IUGR. In order to improve the prognosis of IUGR in affected infants, we investigated the protective role of glutathione in rats exposed to IUGR. Method: Ten female Sprague-Dawley rats were mated overnight. The pregnant rats were divided into 2 groups of 5 rats each. From gestational day 9 until parturition, group A received normal saline while group B received 50 mg/kg daily of L-NAME. Pups from group A were allowed free access to food and water, while group B pups were randomly assigned into 3 groups; G1 pups were left untreated; 1.5g/kg of gluthatione was administered to G2 pups from PND 4-10 and G3 pups from PND 25-31. We measured the body weight of rats; immunolocalized and further quantified TNFα expression in the hepatic and renal tissues. Results: Postnatal GSH administration increased body weight in treated groups exposed to IUGR more significantly from days 4-10 as opposed to days 25-31. IUGR resulted in a significant increase in the TNFα immunoreactivity in the hepatic and renal tissues of the untreated group of rats when compared with the control and treated groups. GSH significantly reduced TNFα immunoreactivity in the kidney and liver of the treated groups, especially the days 4-10. Conclusions: Oral GSH administration regulates the inflammatory response in IUGR at the early neonatal period.

Characterization of TGF-β by Induced Oxidative Stress in Human Trabecular Meshwork Cells

Oxidative stress generated by reactive oxygen species (ROS) plays a critical role in the pathomechanism of glaucoma, which is a multifactorial blinding disease that may cause irreversible damage within human trabecular meshwork cells (HTMCs). It is known that the transforming growth factor-β (TGF-β) signaling pathway is an important component of oxidative stress-induced damage related to extracellular matrix (ECM) fibrosis and activates cell antioxidative mechanisms. To elucidate the dual potential roles and regulatory mechanisms of TGF-β in effects on HTMCs, we established an in vitro oxidative model using hydrogen peroxide (H2O2) and further focused on TGF-β-related oxidative stress pathways and the related signal transduction. Via a series of cell functional qualitative analyses to detect related protein level alterations and cell fibrosis status, we illustrated the role of TGF-β1 and TGF-β2 in oxidative stress-induced injury by shTGF-β1 and shTGF-β2 knockdown or added recombinant human TGF-β1 protein (rhTGF-β1). The results of protein level showed that p38 MAPK, TGF-β, and its related SMAD family were activated after H2O2 stimulation. Cell functional assays showed that HTMCs with H2O2 exposure duration had a more irregular actin architecture compared to normal TM cells. Data with rhTGF-β1 (1 ng/mL) pretreatment reduced the cell apoptosis rate and amount of reactive oxygen species (ROS), while it also enhanced survival. Furthermore, TGF-β1 and TGF-β2 in terms of antioxidant signaling were related to the activation of collagen I and laminin, which are fibrosis-response proteins. Succinctly, our study demonstrated that low concentrations of TGF-β1 (1 ng/mL) preserves HTMCs from free radical-mediated injury by p-p38 MAPK level and p-AKT signaling balance, presenting a signaling transduction mechanism of TGF-β1 in HTMC oxidative stress-related therapies.

Dietary supplementation of Pleurotus tuber regium in rat feed ameliorates metabolic and hematotoxicity induced by carbon tetrachloride.

Pleurotus tuber regium, a wild edible mushroom can reduce free radical-mediated injury and oxidative stress induced by carbon tetrachloride (CCl4) via improvement of antioxidant capacity. This work evaluates the protective effects of this mushroom against the metabolic and hematological toxicity induced by CCl4. Sixty male Sprague Dawley rats were divided into six groups (n = 10). Group I received olive oil (3 mL/kg) i.p. twice weekly for 13 weeks, while maintaining free access to food and water ad libitum (negative control). Group II received 3 mL/kg (30% CCl4 in olive oil) injected i.p. twice weekly, while Groups III, IV, and V received 100, 200, and 500 mg wild edible P. tuber regium (33.3% in feed) daily in addition to 3 mL/kg CCl4 in olive oil injected twice weekly i.p. Group VI received olive oil (3 mL/kg) i.p. twice weekly for 13 weeks in addition to 500 mg P. tuber regium (33.3% in feed) daily. The body weight (b.w.), feed intake (FI), and water intake (WI) were obtained weekly, while the hematological indices and oxidative stress parameters were carried out shortly after necropsy on days 30, 60, and 90. Treatment with CCl4 significantly (p < 0.05) decreased the b.w., FI and WI, feed efficiency, ascorbic acid, α-tocopherol, and antioxidant enzymes, superoxide dismutase, catalase, total glutathione, and peroxidase, while increasing the oxidative stress as measured by malondialdehyde in CCl4 only group when compared with control. Supplementation of feed with P. tuber regium reversed the effects of CCl4. Pleurotus tuber regium ameliorated the CCl4-induced metabolic and hematotoxicity by improving the antioxidant capacity.

Acute Renal Failure - A Serious Complication in Patients After Kidney Transplantation.

Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard.

The role of oxidative stress in organophosphate and nerve agent toxicity.

Organophosphate (OP) nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent OP toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to OP agents. Key findings of these studies include alterations in mitochondrial function and increased free radical-mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in OP neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of OP-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures.

Effect of therapeutic ultrasound and diathermy on oxidant–antioxidant balance in dogs suffering from hind quarter weakness

The present study was conducted to evaluate the erythrocytic oxidant–antioxidant balance in dogs suffering from hind quarter weakness (HQW) and treated with conventional drug therapy (CDT, n=8) alone and in combination with therapeutic ultrasound (US, n=8) and shortwave diathermy (SWD, n=8). A further eight healthy dogs were used as controls. For oxidant level, Lipid Peroxidation (LPO) and antioxidant levels Reduced Glutathione (GSH), Superoxide Dismutase (SOD) and Catalase (CAT) were evaluated in erythrocyte before (day 0) and after 3, 7, 14 and 28 days of therapy. In dogs with HQW, LPO in terms of Malondialdehyde (MDA) production, was found significantly (P<0.05) increased compared to a healthy control on day 0. Thereafter, a significant (P<0.05) decrease in the level of LPO was noticed. Amongst antioxidant enzymes, activities of GSH and CAT decreased significantly (P<0.05) whereas, the level of SOD increased significantly (P<0.05) until day 28 post treatment. Studies revealed that SWD and therapeutic ultrasound in conjunction with CDT can be used to counter free radical-mediated oxidative cell injury, induced by HQW in dogs. However, SWD proved to be better in minimizing excess free radicals production and activating antioxidant defense system as compared to therapeutic ultrasound.

HIV‐1 protein Tat inhibits vesicular monoamine transporter‐2 activity in rat striatum

HIV‐1 protein Tat inhibits vesicular monoamine transporter‐2 activity in rat striatum

Intestinal anti-inflammatory activity of esculetin and 4-methylesculetin in the trinitrobenzenesulphonic acid model of rat colitis

Coumarins comprise a broad class of phenolic compounds that influences the formation and scavenging of reactive oxygen species and the processes involving free radical-mediated injury. In light of the antioxidant and anti-inflammatory properties of esculetin and 4-methylesculetin, the aim of this study was to investigate the effects of these compounds in an experimental model of rat colitis induced by trinitrobenzenesulphonic acid (TNBS). For this purpose, macroscopic (diarrhoea, extension of lesion, colonic weight/length ratio and damage score) and biochemical parameters (myeloperoxidase, alkaline phosphatase and glutathione) were evaluated. Our results reveal that these compounds, particularly 4-methylesculetin, may be effective for the treatment of intestinal inflammatory bowel disease. In the acute colitis model, esculetin promoted a reduction in the extension of the lesion accompanied by a reduction in the incidence of diarrhoea and restoration of the glutathione content. Similar effects were produced by the administration of 4-methylesculetin, which also inhibited the myeloperoxidase and alkaline phosphatase activities in the acute intestinal inflammatory process and in the model of colitis relapse. The effect of the esculetin and 4-methylesculetin on the inflammatory process may be related to their antioxidant and anti-inflammatory properties, as observed in this study. The evidence for better effects of 4-methylesculetin in comparison to those demonstrated by esculetin in both experimental settings could be attributed to the presence of the methyl group at C-4 of 4-methylesculetin.

Oxidative stress disrupts oligodendrocyte maturation.

Periventricular white matter injury (PWMI) is the leading cause of chronic neurologic injury among survivors of preterm birth. The hallmark of PWMI is hypomyelination and a lack of mature, myelinating oligodendrocytes. Oligodendrocytes undergo a well-characterized lineage progression from neural stem cell to mature oligodendrocyte. Oligodendrocyte precursors have increased susceptibility to oxidative and free radical-mediated injury compared with mature oligodendrocytes as a result of lower levels of antioxidant enzymes and free radical scavengers. In this study, we show that oxidative stress disrupts oligodendrocyte differentiation by two mechanisms. First, oxidizing agents decrease the expression of key genes that promote oligodendrocyte differentiation from neural stem cells and increase the expression of genes known to inhibit differentiation. Second, global histone acetylation persists under conditions of oxidative stress, further contributing to the prevention of oligodendrocyte differentiation. Both of these mechanisms result in the arrest of oligodendrocyte differentiation without an increase in cell death.

Ischemia/Reperfusion Injury in Kidney Transplantation: Mechanisms and Prevention

Ischemia has been an inevitable event accompanying kidney transplantation. Ischemic changes start with brain death, which is associated with severe hemodynamic disturbances: increasing intracranial pressure results in bradycardia and decreased cardiac output; the Cushing reflex causes tachycardia and increased blood pressure; and after a short period of stabilization, systemic vascular resistance declines with hypotension leading to cardiac arrest. Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that all of these changes—the early innate response and the ischemic tissue damage—play roles in the development of adaptive responses, which in turn may lead to an acute font of kidney rejection. Hypothermic kidney storage of various durations before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion. Reperfusion injury, the effector phase of ischemic injury, develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy, and necrosis; the fate of the organ depends on whether cell death or regeneration prevails. The whole process has been described as the ischemia-reperfusion (I-R) injury. It has a profound influence on not only the early but also the late function of a transplanted kidney. Prevention of I-R injury should be started before organ recovery by donor pretreatment. The organ shortage has become one of the most important factors limiting extension of deceased donor kidney transplantation worldwide. It has caused increasing use of suboptimal deceased donors (high risk, extended criteria [ECD], marginal donors) and uncontrolled non–heart-beating (NHBD) donors. Kidneys from such donors are exposed to much greater ischemic damage before recovery and show reduced chances for proper early as well as long-term function. Storage of kidneys, especially those recovered from ECD (or NHBD) donors, should use machine perfusion.

The Anti-inflammatory Effect of Coumarin and its Derivatives

Inflammation is the primary host defense mechanism against all forms of injury. Excessive or inadequate activation of the system can have serious effects, as can the failure of inactivation mechanisms. Coumarins can reduce tissue edema and inflammation and inhibit prostaglandin biosynthesis, which involves fatty acid hydroperoxy intermediates. It is to be expected that coumarins might affect the formation and scavenging of reactive substances derived from oxygen species (ROS) and influence processes involving free radical-mediated injury, as can flavonoids. During these years a small number of (Q)SAR studies concerning coumarins as NSAIDs has been presented and reviewed. In this research we tried to examine the structure-function relationship for coumarins, presenting antiinflammatory activity. Coumarin (1), the prototypical compound presents anti-inflammatory activity. The hydroxylaromatic substituted derivatives (5- or 6- or 7-hydroxy or the vicinal dihydroxy) seems to be potent inhibitors of lipoxygenase. Several synthetic derivatives simple or more complicated were found to be potent antiinflammatories/antioxidant agents.

Specific oxidative stress parameters differently correlate with nailfold capillaroscopy changes and organ involvement in systemic sclerosis

Oxidative stress is suggested to be involved in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to clarify such a hypothesis by determination of four different plasmatic parameters of oxidative stress, and to define its role in the microvascular damage, assessed by nailfold capillaroscopy (NC). Plasma samples of 18 patients with SSc were analyzed. The biomarkers measured were: total antioxidant capacity, hydroperoxides (ROOHs), and sulfhydryl (SH) and carbonyl (CO) groups. Each patient had a detailed clinical assessment and underwent an NC. The results showed significantly increased ROOHs in SSc patients compared to control group (5.02 +/- 0.24 vs 3.28 +/- 0.19 micromol/l; p < 0.05). Plasmatic levels of SH groups were significantly lower in SSc (0.466 +/- 0.08 mmol/l) compared to control group (0.542 +/- 0.04 mmol/l; p < 0.002). Plasma levels of ROOHs correlated with the capillaroscopy semiquantitative rating scale score (p < 0.05) and with the rating system for avascular areas (p < 0.03). The levels of CO groups inversely correlated with modified Rodnan's skin score (p < 0.039) and were lower in patients with pulmonary fibrosis (p < 0.045), while the levels of SH groups were lower in those presenting gastrointestinal involvement (p < 0.029). The obtained data indicate augmented free radical-mediated injury in SSc and also show correlations among oxidative abnormalities, some clinical findings, and signs of a more severe microvascular involvement. These results give more evidence to the connection between oxidative impairment and SSc.

Cerebral White Matter Injury

Despite advances in neonatal intensive care, periventricular white matter injury (PWMI) remains the most common cause of brain injury in preterm infants and the leading cause of chronic neurologic morbidity. Factors implicated in the pathogenesis of PWMI during prematurity include hypoxia, ischemia, and maternal-fetal infection. PWMI is recognized increasingly in term newborns who have congenital heart disease. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia [PVL]) and diffuse myelination disturbances. Information about the prevalence, severity, and distribution of white matter lesions has relied heavily on neuropathology studies of autopsy brains. However, advances in magnetic resonance imaging of the neonatal brain suggest that the incidence of PVL is declining; focal or diffuse noncystic injury is emerging as the predominant lesion. Insight into the cellular and molecular basis for these shifting patterns of injury has emerged from recent studies with several promising experimental models. These studies support the suggestion that PWMI can be initiated by impaired cerebral blood flow related to anatomic and physiologic immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible late oligodendrocyte progenitors. It is anticipated that new strategies for prevention of brain injury in preterm infants will develop as a result of improved recognition of changing patterns of injury that reflect specific types of cellular vulnerability.

Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail

Oxidative stress and increased oxidation of low-density lipoprotein (oxLDL) through free radical-mediated tissue injury may be important factors in the development of extracranial atherosclerotic lesions. However, the roles of oxidative stress and hypercholesterolemia in intracranial atherosclerosis is less established. The induction of heme oxygenase (HO) is a cellular response to oxidative stress, and inducible HO (HO-1) may protect against oxidized lipids such as those produced by oxidative stress. We investigated the effects of oxLDL on cell and tissue viability, HO-1 and ferritin expression in extracranial and intracranial endothelial cells, and the arteries of cholesterol-induced atherosclerosis (CIA) Japanese quail. We report that cultured microvascular endothelial cells from the brain (QBMEC) and carotid (QCEC) differ in their response to oxidative stress. The QCECs are less responsive than QBMECs to oxidative stress induced by oxLDL, as evident by lower expression of HO-1 mRNA, HO activity, and ferritin levels. Furthermore, the higher levels of catalytic iron, thiobarbituric acid reactive substances, and lactate dehydrogenase released in QCECs indicated that these cells are more susceptible to oxidative stress than QBMECs. We also investigated the relationship between extent of atherosclerotic plaque deposition and the extracranial and intracranial arterial expression of HO-1 in quail. The common carotid and vertebral (extracranial) arteries had higher tissue cholesterol levels (starting at 2 weeks of cholesterol-supplementation) and a greater atherosclerotic plaque score (starting at 4 weeks of cholesterol-supplementation) compared with middle cerebral and basilar (intracranial) arteries, and this may be relevant to the effect of aging on the process of atherogenesis. The extracranial arteries also had early and greater levels of lipid peroxidation and catalytic iron coupled with lower expression of HO-1 protein, HO activity, and ferritin compared to the intracranial vessels. These observations suggest that the extracranial and intracranial arterial walls respond differently to oxidation of lipoproteins, and support the feasibility of increased HO-1 expression as a means of protection against oxidant injury.

Neuroprotection and thrombolysis: combination therapy in acute ischaemic stroke

The administration of oral aspirin within 48 h and tissue plasminogen activator within 3 h of ischaemic stroke onset remain the only treatments that have been shown to have clinical benefit. There has been much excitement about neuroprotection over the last two decades, as it may minimise the harmful effects of ischaemic neuronal damage. Although each step along the ischaemic cascade offers a potential target for therapeutic intervention, and neuroprotection has shown benefit in animal studies, this has been difficult to translate to humans. Some hope has been offered by the recent finding that the free radical scavenger NXY-059 may improve outcomes in patients presenting within 6 h of onset of ischaemic stroke. There is logic to the idea that neuroprotection may be most effective when reperfusion has occurred with thrombolysis, as the neuroprotectant will have greater access to ischaemic tissue and the opportunity is presented to minimise free radical-mediated reperfusion injury. Numerous studies in animal models support this view, but the concept has not, as yet, been rigorously tested in humans.

Oxidative stress parameters in different systemic rheumatic diseases

The involvement of oxidative stress in the pathogenesis of rheumatic disorders, such as systemic sclerosis (SSc) and chronic polyarthritides, has been suggested yet not thoroughly verified experimentally. We analysed 4 plasmatic parameters of oxidative stress in patients with SSc (n = 17), psoriatic arthritis (PsA) (n = 10) and rheumatoid arthritis (RA) (n = 9) compared with healthy subjects (n = 22). The biomarkers were: total antioxidant capacity (TAC) measured by ferric reducing antioxidant power (FRAP) method, hydroperoxides determined by ferrous ion oxidation in presence of xylenol orange (FOX) method and sulfhydryl and carbonyl groups assessed by spectrophotometric assays. The results showed significantly increased hydroperoxides in SSc, PsA and RA (3.97 +/- 2.25, 4.87 +/- 2.18 and 5.13 +/- 2.36 micromol L(-1), respectively) compared with the control group (2.31 +/- 1.40 micromol L(-1); P < 0.05). Sulfhydryls were significantly lower in SSc (0.466 +/- 0.081 mmol L(-1)), PsA (0.477 +/- 0.059 mmol L(-1)) and RA (0.439 +/- 0.065 mmol L(-1)) compared with the control group (0.547 +/- 0.066 mmol L(-1); P < 0.05). TAC in all three diseases showed no difference in comparison with controls. Carbonyls were significantly higher in RA than in the control group (32.1 +/- 42 vs 2.21 +/- 1.0 nmol (mg protein)(-1); P < 0.05). The obtained data indicate augmented free radical-mediated injury in these rheumatic diseases and suggest a role for the use of antioxidants in prevention and treatment of these pathologies.

Lipid peroxidation, occupational stress and aging in workers of a prehospital emergency service

Stressful conditions lead to formation of excessive free radicals, and lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products. To determine the levels of malondialdehyde, an end product of lipid peroxidation, according to demographic and occupational variables in workers of a prehospital emergency service and to analyse the relationship between malondialdehyde levels and burnout. One hundred and eleven healthy workers of a prehospital emergency service and eighty aged-matched healthy individuals of both sexes as a control group were surveyed. Malondialdehyde levels were measured by the Bull and Marnett method. To measure burnout, the Maslach Burnout Inventory was used. Professional category is associated with lipid peroxidation and burnout levels (Malondialdehyde levels were: physicians 338.10+/-14.47, nurses 329.17+/-12.62 and technicians 296.74+/-14.28; burnout levels were: physicians 41.29+/-3.59, nurses 37.38+/-6.05 and technicians 35.33+/-5.87). Working at night and in the evening increased malondialdehyde and burnout levels. Malondialdehyde levels increase with age. No significant variations with respect to sex were detected. Significant variations in malondialdehyde levels were detected between singles (303.13+/-12.74) and married people (344.43+/-13.43) but not with respect to divorcees (326.44+/-11.74). Significant differences were detected in erythrocyte malondialdehyde levels between smokers (341.37+/-17.09) and nonsmokers (302.21+/-12.38), but not for alcohol consumption. These findings suggest a positive correlation between malondialdehyde, a biomarker of lipid peroxidation and occupational stress, as estimated by elements of the Maslach Burnout Inventory, and oxidative stress.