Pulsed ultrasound and dimethylsulfoxide gel treatment reduces the expression of pro-inflammatory molecules in an animal model of muscle injury

Studies have shown an exacerbated increase in proinflammatory markers during and after muscle injury. In this way, interventions that reduce inflammatory activation appear to be of great interest in muscle injury therapy. Thus, the preset study evaluated the effect of low-intensity pulsed ultrasound (LIPUS) and dimethylsulfoxide (DMSO) on the proinflammatory molecules in an animal model of traumatic muscle injury. Forty-eight 3-month old male Wistar rats were divided into six groups (n = 8/group): sham; muscle injury without treatment; muscle injury and gel-saline (0.9%); muscle injury and gel-DMSO (15 mg/kg); muscle injury and LIPUS plus gel-saline; and muscle injury and LIPUS plus gel-DMSO. Two, 12, 24 and 48 h after trauma, four groups received one of the treatments described. One hour after, Western blot was performed to quantify proinflammatory protein levels. We observed greater protein levels of TNFα (3.9 times), IL-1β (3.6 times), JNK phosphorylation (4.2 times) and NFκB (3.8 times) in muscle injury group. However, the combined LIPUS with DMSO resulted in significantly lower levels of TNFα (2.2 times), IL-1β (2.1 times), JNK phosphorylation (2.4 times), and NFκB (2.1 times). The results demonstrate that LIPUS associated with DMSO gel can attenuate TNFα, IL-1β, NFκB protein levels and JNK phosphorylation in traumatic muscle injury.     

Effect of Phonophoresis and Copaiba Oil on Oxidative Stress Biomarkers after Skeletal Muscle Injury in Rats

The objective of this study was to analyze the effectiveness of phonophoresis with copaiba oil gel, in comparison to therapeutic pulsed ultrasound alone or topical application of copaiba oil gel, on oxidative stress after a traumatic muscle injury. Forty male Wistar rats were divided into five groups: control, muscle injury, therapeutic pulsed ultrasound (TPU), copaiba oil gel (CO) and TPU plus CO. TPU and CO application occurred at 2, 12, 24, 48, 72 and 96 h after injury. The gastrocnemius muscle was injured by mechanical trauma. Malondialdehyde (a lipoperoxidation marker) and superoxide dismutase and catalase (antioxidant enzymes) were assessed 98 h after muscle injury. All were elevated in the muscle injury group. There was a significant difference among treatment groups favoring TPU plus CO for reducing malondialdehyde levels, but all treatments reduced superoxide dismutase and catalase activity, with no between-groups difference. In conclusion, phonophoresis—the application of TPU plus CO—was superior to TPU or CO alone for reducing lipoperoxidation. Phonophoresis, TPU alone and CO were all effective in decreasing antioxidant enzyme activity after a traumatic skeletal muscle injury.     

Effect of Pulsed Therapeutic Ultrasound and Diosmin on Skeletal Muscle Oxidative Parameters

Cyclodextrins (CDs) have been widely used as a promising alternative in the formation of inclusion complexes with poorly soluble molecules. From this perspective, the present study aimed to study the inclusion complexes of diosmin in β-cyclodextrin, chemically quantify the diosmin-in-gel preparation and analyze the stability of the gels. Furthermore, we evaluated the effect of therapeutic pulsed ultrasound (TPU) in association with the gel–diosmin complex on the parameters of muscle damage and oxidative stress in rats. Serum creatine kinase (CK) levels were used as an indicator of skeletal muscle injury. Lipid peroxidation (thiobarbituric acid-reactive substances [TBARS]) and superoxide dismutase and catalase activities were used as indicators of oxidative stress. The results obtained indicated that the inclusion complex obtained by co-evaporation had the highest complexation efficiency and stability; there was no change in the features of diosmin on incorporation into the Carbopol gel. Additionally, a significant (p?<0.05) decrease was observed in CK levels (TPU?plus gel-diosmin: 178.4?±?85.3?U/L) relative to the untreated group (527.8?±?46.1?U/L). Levels of TBARS were lower in the TPU?plus gel-diosmin group (0.008?±?0.0004?nmol malondialdehyde/mg protein, p?<0.05) compared with the untreated group (0.081?±?0.011?nmol malondialdehyde/mg protein, p?<0.05, n?=?6). Catalase activity did not statistically significantly differ between the treatment groups, and superoxide dismutase activity was lower in the diosmin-treated group (0.320?±?0.11?U/mg protein) compared with the untreated group (0.983?±?0.40?U/mg protein). These results suggest that TPU in association with the diosmin–gel complex is effective in reducing muscle damage and oxidative stress after mechanical trauma.     

A novel quercetin/β-cyclodextrin transdermal gel,combined or not with therapeutic ultrasound,reduces oxidative stress after skeletal muscle injury

A gel containing the inclusion complex of quercetin and β-cyclodextrin was developed in order to verify its effects, isolated or using phonophoresis, on oxidative biomarkers after skeletal muscle injury. 30 male rats were divided into one of five groups: Control (CTRL), Muscle Injury (MI), Therapeutic Pulsed Ultrasound (TPU), Therapeutic Pulsed Ultrasound plus Quercetin (TPU plus gel-QUE) or Quercetin gel (QUE). Quercetin gel was complexed with β-Cyclodextrin (β-CD) using chromatography (HPLC). TPU and quercetin application occurred with 2, 12, 24, 48, 72, 96 hours intervals after injury. Gastrocnemius muscle was injured by mechanical trauma. Lipid peroxidation, superoxide dismutase activity, and catalase activity were assessed. The inclusion complex exhibited adequate entrapment efficiency, relative density and pH. The viscosity of the complex showed a non-Newtonian pseudoplastic behavior. Quercetin/β-cyclodextrin gel reduced lipid peroxidation, superoxide dismutase activity and catalase activity compared to muscle injury group. Similarly, phonophoresis and TPU also reduced the levels of these oxidative biomarkers. In conclusion, quercetin/β-cyclodextrin transdermal gel reduces oxidative stress biomarkers after skeletal muscle injury irrespective of using phonophoresis.

A gel containing the inclusion complex of quercetin and β-cyclodextrin was developed in order to verify its effects, isolated or using phonophoresis, on oxidative biomarkers after skeletal muscle injury.     

Combined vitamins (C and E) and insulin improve oxidative stress and pancreatic and hepatic injury in alloxan diabetic rats

The aim of the present study is to determine if a combination of vitamins (C and E) has any advantage over insulin therapy on lipid peroxidation, antioxidant activity, liver dysfunction parameters, and histological changes in the alloxan-induced diabetic rats. The enzymatic activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) and the lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS) were measured in liver and pancreas as indicators of antioxidation in these tissues. The liver dysfunction parameters: the activity of lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT), phosphatase alkalines (PAL), aspartate and lactate transaminase (AST and ALT) were measured in serum. In diabetic rats, the TBARS contents of the liver and pancreatic tissues were found to have significantly increased as compared to non-diabetic rats (P < 0.001). The SOD, CAT, and GPX activities in the liver and pancreas in diabetic rats significantly decreased as compared to normal rats (P < 0.001). AST, ALT, LDH, GGT, and PAL activities increased in the diabetic rats (p > 0.05). In diabetic rats treated with insulin or with combined vitamins (C and E), an ameliorative effect was observed. This amelioration was more pronounced in the group of rats treated with combined vitamins (C and E).     

Evidence of oxidative stress in the circulation of ovarian cancer patients

BACKGROUND: Ovarian cancer is the leading cause of death due to gynecological malignancies among women. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant mechanisms. The present study was conducted to investigate the extent of oxidative stress and the levels of antioxidants in the circulation of ovarian cancer patients. METHODS: Plasma thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) and the levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), vitamin C and vitamin E were estimated in the circulation of 30 ovarian cancer patients and an equal number of age-matched normal subjects as control. RESULTS: Significantly increased concentrations of plasma TBARS and CD and significantly lowered levels of SOD, CAT, vitamin C and vitamin E were observed in ovarian cancer patients as compared with normal subjects. CONCLUSION: The low levels of SOD, CAT, vitamin C and vitamin E in the plasma of ovarian cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells. Increased levels of lipid peroxidation may be due to excessive oxidative stress caused by incessant ovulation or epithelial inflammation.     

Relationship between neurological outcome and early oxidative changes in erythrocytes in head injury patients.

BACKGROUND: Experimental data indicate that destructive oxidative events reach their peak within the first 24 h after trauma in head injury (HI) and that brain damage occurring due to this impact can be the cause of death or irreversible permanent disabilities in affected patients. METHODS: Venous blood samples were obtained from 50 HI patients within 24 h of trauma onset and from 30 age- and sex-matched normal controls (NC). Patients were divided into three different neurological outcome groups: those who died within 10 days of trauma (D), and those with severe neurological deficits (SD) or mild/no neurological deficits (MD) at 90 days after trauma. Early oxidative changes in erythrocytes were assessed by estimating an indicator of lipid peroxidative damage - thiobarbituric acid-reactive substances (TBARS) - and antioxidants [reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity]. RESULTS: In the D group, erythrocyte TBARS levels were significantly higher compared to the NC, SD and MD groups (p<0.001); GSH levels were significantly lower compared to the NC (p<0.001) and MD (p<0.01) groups and SOD activity was significantly higher than in the NC (p<0.01) and MD (p<0.01) groups. In the SD group, TBARS levels were significantly higher than in the NC (p<0.001) and MD (p<0.05) groups; GSH levels were significantly lower than in the NC (p<0.001) and MD (p<0.01) groups and SOD activity was higher compared to the NC and MD (p<0.01) groups. In the MD group, TBARS levels were significantly higher and GSH levels significantly lower compared to the NC group (p<0.001). However, we did not observe any significant change in SOD activity compared to the NC group. CONCLUSIONS: These findings indicate that early oxidative changes may reflect the severity of neurological insult and provide an early indication of patient outcome in traumatic HI.     

Antioxidant potential of vitamins A, E and C in modulating oxidative stress in rat brain

Background: Stress is known to affect synaptic plasticity, dendritic morphology and induces neurotoxic damage in humans, probably through generation of free radicals. Both ex vivo antioxidant vitamins and in vivo free radical scavenging enzymes exist. In the present study, restraint stress induced pro-oxidant status of rat brain was evaluated in terms of measurement of glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and free radical scavenging enzymes activities. The efficacy of antioxidant vitamins A, E and C alone and in combination was also evaluated in modulating inherent antioxidant system in stressed rats. Methods: Rats were treated with vit A, E and C alone (15 mg/kg of body weight) and in combination vitamins (E and C) prior to and after 6 h of restraint stress exposure. Both nonstressed and stressed rats were handled simultaneously. Pro-oxidant status of brain tissue was evaluated by determining the levels of GSH, TBARS and activities of superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT). Results: Restraint stress induced a decrease in the level of GSH and the activities of SOD, GST and catalase, while the levels of TBARS were found elevated. Both pre-stress and post-stress vitamin treatments (either alone or combined) resulted in alteration of these parameters towards their controls values with a relative dominance by latter. Vitamin E was found most effective in restoring inherent antioxidant system, no additive effect was observed in combined vitamin treatment as expected. Conclusion: Immobilization of rats generated oxidative stress in rat brain, by decreasing the activities of SOD, GST, catalase and glutathione levels, while increasing the lipid peroxidation. Post stress vitamin E treatment was found most effective than vitamins A and C in enhancing the levels of glutathione and activities of SOD, GST and catalase and decreasing lipid peroxidation. Thus vitamin E can be given as a nutritional supplement for scavenging free radical generated in the brain tissues in order to reduce oxidative stress.     

Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients

ObjectivesTo evaluate the oxidative status and antioxidant defense in patients with acute lymphoblastic leukemia (ALL).Design and methodsWe measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasmatic and erythrocyte thiol levels and serum vitamin E concentration. This study was performed on 80 children with ALL divided into 4 groups: just diagnosed, remission induction, remission maintenance and out-of-treatment.ResultsTBARS levels and serum protein carbonylation were higher in ALL patients than in controls and reduced levels of antioxidants were found in these patients.ConclusionThese findings may indicate a possible link between decreased antioxidants and increased levels of cells alterations due to oxidative damage, supporting the idea that there is a persistence of oxidative stress in acute lymphoblastic leukemia.     

Carvedilol attenuates ischemia-reperfusion-induced oxidative renal injury in rats

There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of carvedilol (CVD), an antihypertensive drug in I/R-induced renal failure in rats. The protective effect of CVD against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments, animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Carvedilol (2 mg/kg, i.p.) was administered twice, 30 min prior to ischemia and 12 h after the reperfusion period. At the end of the reperfusion period, rats were killed. Thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with CVD markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R-induced renal injury and CVD exerts renoprotective effects probably by the radical scavenging and antioxidant activities.     

Elevated lipid peroxidation and disturbed antioxidant enzyme activities in plasma and erythrocytes of patients with uterine cervicitis and myoma.

OBJECTIVES: We investigated whether oxidative stress is associated with human uterine cervicitis and uterine myoma. DESIGN AND METHODS: We measured lipid peroxidation and antioxidant enzymes in plasma and erythrocytes of cervicitis patients and myoma patients in comparison with matched controls. Thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, were determined in plasma; glutathione peroxidase (GSHPx) and catalase in erythrocytes; and superoxide dismutase (SOD) in both plasma and erythrocytes. RESULTS: We showed that plasma TBARS were significantly higher (p < 0.05) in both cervicitis patients and myoma patients than in controls. Plasma TBARS were significantly (and negatively) correlated with plasma and erythrocyte T-SOD activities in cervicitis patients only. Plasma T-SOD activity was significantly lower in both groups of patients than in controls whereas erythrocyte T-SOD activity was only significantly lower in myoma patients. The lowered plasma T-SOD activity in the cervicitis patients was attributed to decreased Mn-SOD activity whereas the lowered plasma T-SOD activity in myoma patients was attributed to decreased activities of both Cu,Zn-SOD and Mn-SOD. Erythrocyte GSHPx activity was 14% higher (p < 0.05) in cervicitis patients and 11% lower (p > 0.05) in myoma patients than in controls; catalase activity was 10% higher (p > 0.05) in cervicitis patients and 13% lower (p > 0.05) in myoma patients than in controls. Neither erythrocyte GSHPx nor catalase activity was significantly correlated with plasma TBARS. CONCLUSIONS: The elevated lipid peroxidation and disturbed antioxidant enzyme activities demonstrate the potential of oxidative injury in patients with uterine cervicitis and myoma.     

Plasma oxidative parameters and mortality in patients with severe burn injury

OBJECTIVE: To determine xanthine oxidase and superoxide dismutase activities, lipid peroxidation, protein carbonylation, and total radical-trapping antioxidant parameter in survivors and nonsurvivors patients with severe burn injury. DESIGN AND SETTING: Prospective, comparative observational study in an intensive care unit, burn division, in a trauma hospital. PATIENTS: Twenty-five consecutive patients who met the established criteria for severe burn injury (total burn surface area of more than 30%). MEASUREMENTS AND RESULTS: Plasma thiobarbituric acid reactive species and protein carbonyls levels were significantly higher in nonsurvivors than in survivors at 0 and 6 h. Elevated xanthine oxidase activity at 0 h was associated with adverse outcome after burn injury. In contrast, plasma superoxide dismutase activity and total radical-trapping antioxidant parameter did not differ significantly between nonsurvivors and survivors at any time point. CONCLUSIONS: For the first time we demonstrate the value of oxidative parameters, namely thiobarbituric acid reactive species, protein carbonyls, and xanthine oxidase activity, in identifying burn patients with a poor prognosis. Whether these parameters are merely markers of clinical course, or whether they signal specific deleterious effects of oxidative stress during the burn injury remains to be elucidated.     

δ-aminolevulinate dehydratase activity in lung cancer patients and its relationship with oxidative stress

This study investigated the δ-aminolevulinate dehydratase (δ-ALA-D) activity in whole blood as well as the parameters of oxidative stress, such as reactive species (RS) levels in serum, thiobarbituric acid reactive substances (TBARS) levels, the superoxide dismutase (SOD) and catalase (CAT) activities, as well as total thiols (T-SH) and non-protein thiols (NPSH) levels in platelets. Moreover, the content of vitamin C and E in plasma and serum, respectively, in lung cancer patients was also investigated. We collected blood samples from patients (n = 28) previously treated for lung cancer with chemotherapy. Patients were classified as stage IIIb and IV according to the Union for International Cancer Control (UICC). Results showed a decrease of 37% in δ-ALA-D activity in patients with lung cancer when compared to the control group. RS and TBARS levels were 8% and 99% higher in the patient group, respectively. The activity of SOD and CAT as well as the vitamin C content were 41%, 35% and 127% lower in patients when compared with controls, respectively. However, T-SH and vitamin E levels were 27% and 44% higher in lung cancer patients, respectively. Results show that the overproduction of reactive species in patients with lung cancer may be interfering with the activity of δ-ALA-D. Likewise, the decrease in the activity of this enzyme may be contributing for the oxidative stress.     

Total bilirubin in young men and women: Association with risk markers for cardiovascular diseases

Objective

The aim of this study was to investigate whether high bilirubin concentration is a protective factor in cardiovascular disease (CAD) and how it correlates with parameters of oxidative stress in young males and females.

Methods

The study comprised 628 healthy subjects of both genders, 18–22 years of age. In fasting sera the concentration of total bilirubin (Tbil), parameters of cardiovascular risk and oxidative stress were determined. The results were analyzed by appropriate statistical methods.

Results

We found no gender differences in body mass index (BMI), blood pressure and lipid profile between subjects with low and high Tbil level. Men with high Tbil had higher concentrations of albumin and uric acid (p < 0.001) and lower of oxLDL (< 0.05), while women had higher albumin (p < 0.05) and lower TBARS (p < 0.05). Significant positive correlation in men was found between Tbil, uric acid and albumin, while for glucose and TBARS this association was negative. In female significant positive correlation was between Tbil, HDL-C, fibrinogen, albumin and uric acid and negative between Tbil and TBARS. The high concentration of Tbil in men was independently associated with uric acid (p < 0.05) and oxLDL (p < 0.001), while in women it was independently associated with TBARS (p < 0.05). After adjustment for traditional lipid parameters the predictive power of high bilirubin in men remained for uric acid (p < 0.001) and TBARS in women (p < 0.05).

Conclusion

These findings jointly support the concept that bilirubin via its antioxidant potential has a protective effect against cardiovascular disease in young male and female.     

Protective role of luteolin on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis

The modifying effect of dietary exposure to a flavonoid, luteolin (LUT) during the azoxymethane (AOM)-induced colon carcinogenesis was investigated in this study. Aberrant crypt foci (ACF), lipid peroxidation (LPO), enzymic and non-enzymic antioxidants and histopathological analysis were performed. Colon carcinogenesis was induced by injecting 15 mg/body kg weight of AOM, intraperitoneally (i.p.), once in a week for 3 weeks in male Balb/c mice. AOM-induced mice were treated with LUT (1.2 mg of LUT/kg body weight/day orally). After the experimental period, frequency of ACF, levels of thiobarbutaric acid reactive substances (TBARS) and hydroxy radical (OH˙) were found to be increased, whereas glutathione (GSH), Vitamins C, E and A were decreased in the plasma and colon of AOM-induced mice. However, LUT treatment to AOM-induced mice significantly decreased the incidence of ACF, levels of TBARS and OH˙ with a concordant increase in non-enzymic antioxidants in plasma and colon tissue. The activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were found to be decreased due to the induction of colon cancer in mouse. LUT treatment ameliorated the activities of these antioxidant enzymes. The histological study revealed a significant increase in the enlarged nuclei and hyperchromatism of cells in AOM-induced mice whereas LUT significantly reduced the signs in the colon. The immunohistochemical expression of MDA-DNA adduct was studied. In AOM-induced group, the expression was increased and treatment with LUT decreased significantly. The present study depicts that LUT can act as an effective chemopreventive agent against colon cancer.     

Platonin mitigates acute lung injury in haemorrhagic shock rats

Aim of the study

Enhanced oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by haemorrhagic shock with resuscitation. Platonin, a potent antioxidant, possesses potent anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury in haemorrhagic shock/resuscitation rats.

Methods

Seventy-two adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus platonin (10, 50, or 100 μg/kg intravenous injection immediately after resuscitation), sham instrumentation (Sham), or Sham plus platonin (100 μg/kg) (n = 12 in each group). Haemorrhagic shock was induced by blood drawing and mean blood pressure was maintained at 40-45 mmHg for 120 min. Then, resuscitation was achieved by shed blood/saline mixtures re-infusion. After monitoring for another 8 h, rats were sacrificed.

Results

Arterial blood gas and histological findings, in concert with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that haemorrhagic shock/resuscitation caused significant lung injury. Significant increases in concentrations of inflammatory molecules (chemokine, cytokine, and prostaglandin E₂) as well as nitric oxide and malondialdehyde in lung tissues confirmed that haemorrhagic shock/resuscitation elicited inflammatory response and imposed oxidative stress in rats. Platonin at the dosages of 50 and 100 μg/kg, but not 10 μg/kg, significantly attenuated the inflammatory response and oxidative stress induced by haemorrhagic shock/resuscitation. Most important, platonin at the dosages of 50 and 100 μg/kg, but not 10 μg/kg, significantly mitigated the lung injury induced by haemorrhagic shock/resuscitation.

Conclusions

Platonin mitigates acute lung injury in haemorrhagic shock/resuscitation rats.     

Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide-induced acute lung injury in the rat

OBJECTIVES: Interventions that reduce the generation or the effects of reactive oxygen species exert controversial effects in animal models of lung injury, and these could be secondary to the pro-oxidant effects of antioxidants generally by their interaction with iron. We here describe the effects of N-acetylcysteine, deferoxamine, or both in the treatment of acute lung injury induced by intratracheal lipopolysaccharide injection. DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 200-250 g. INTERVENTIONS: Rats exposed intratracheally to lipopolysaccharide were treated with N-acetylcysteine (20 mg/kg subcutaneously 3, 6, and 12 hrs after lipopolysaccharide instillation), deferoxamine (20 mg/kg subcutaneously 3 hrs after lipopolysaccharide instillation), N-acetylcysteine (20 mg/kg, 3, 6, and 12 hrs after lipopolysaccharide instillation) plus deferoxamine (20 mg/kg 3 hrs after lipopolysaccharide instillation), or vehicle. MEASUREMENTS AND MAIN RESULTS: Acute lung injury was induced by intratracheal instillation of lipopolysaccharide in Wistar rats. The animals were randomly divided into five groups: group 1, control with instillation of isotonic saline; group 2, lipopolysaccharide treated with saline; group 3, lipopolysaccharide treated with N-acetylcysteine; group 4, lipopolysaccharide treated with deferoxamine; and group 5, lipopolysaccharide treated with N-acetylcysteine plus deferoxamine. Several times after lipopolysaccharide instillation, the rats were killed and a bronchoalveolar lavage was performed to determine thiobarbituric acid reactive species, protein carbonyls, superoxide dismutase and catalase activities, mitochondrial superoxide production (oxidative stress variables), the degree of the alveolar-capillary membrane compromise, and inflammatory infiltration. Samples from the lung were isolated and assayed for oxidative stress variables or histopathologic analyses. N-acetylcysteine plus deferoxamine decreased bronchoalveolar lavage fluid protein, inflammatory cells, oxidative damage variables, and proinflammatory cytokines. N-acetylcysteine plus deferoxamine treatment significantly attenuated lung oxidative damage, mitochondrial superoxide production, and histopathologic alterations after lipopolysaccharide instillation. CONCLUSIONS: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine decreases oxidative stress and mitochondrial dysfunction and limits inflammatory response and alveolar pathology induced by lipopolysaccharide in the rat.     

Oxidative stress in hypercholesterolemia and its association with Ala16Val superoxide dismutase gene polymorphism

ObjectivesTo investigate the role of the oxidative stress and the antioxidant system as well as the influence of the manganese superoxide dismutase (Ala16Val) polymorphism on hypercholesterolemia.Design and methodsLevels of glucose, lipid, high-sensitivity C reactive protein (hs-CRP), thiobarbituric acid reactive substances (TBARS), carbonyl protein, thiols, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and vitamin C, vitamin E, as well as the presence of the manganese superoxide dismutase (Ala16Val) polymorphism were determined in 40 subjects with hypercholesterolemia and 40 controls.ResultsLipid profile, hs-CRP, glucose, TBARS, carbonyl protein, CAT, and vitamin E were significantly higher in subjects with hypercholesterolemia. In contrast, GSH and SOD were lower. TBARS, carbonyl protein, thiols, CAT, and vitamin E were significantly higher in hypercholesterolemic subjects with VV genotype for MnSOD, while GSH, SOD, and vitamin C were lower in these subjects.ConclusionsWe suggest an association between the genotypes of MnSOD, hypercholesterolemia, and oxidative stress biomarkers.     

Correlation of increased oxidative stress to body weight in disease-free post menopausal women

ObjectivesOxidative stress increases postmenopausally, an effect attributed to aging. Increase in body weight generally accompanies menopause. Obesity per se also seems to increase oxidative stress. The question is whether postmenopausal increase in oxidative stress is related to body weight, or is only a function of age.Design and methodsAge, body weight, and superoxide dismutase (SOD), catalase (CAT) and malonyldialdehyde (MDA) in erythrocytes of a cross-section of 90 disease-free women aged 25–65 years, divided into three groups of n = 30 each of normally menstruating Controls (C), perimenopausal (periM) and postmenopausal women (postM) were recorded.ResultsPostM had the highest oxidative stress and body weight. SOD, CAT and MDA correlated significantly with body weight (? 0.74, 0.64 and 0.69 respectively). The odds of having a lower SOD (OR9.5, 95% CI:2.9–30.8) and higher CAT (OR6.2, 95% CI:1.6–23.0) and MDA (OR6.8, 95% CI:2.7–16.8) for weight > 60 kg was highly significant.ConclusionsOxidative stress is enhanced as body weight increases.     

Association between sperm quality, oxidative stress, and seminal antioxidant activity

Objectives

To determine seminal antioxidant capacity, oxidative stress markers, and their association with semen quality as oxidative stress is considered to be a major etiological factor in male infertility.

Subjects and methods

Semen samples were obtained from 138 men and categorized on the basis of sperm count, motility, and morphology. Seminal oxidative and antioxidant markers are as follows: lipid peroxidation (LPO), protein carbonyls (PC), superoxide dismutase (SOD), catalase (CAT), thiols, and ascorbic acid were determined.

Results

Sperm count significantly correlated positively with progressive sperm motility and normal morphology. Sperm count and normal morphology showed significant negative correlation with LPO and PC. Sperm count and progressive motility showed significant positive relationship with SOD. The SOD, CAT, and thiols positively whereas LPO and PC negatively associated with elevated sperm count.

Conclusion

Insufficient antioxidant enzymes and increased oxidative stress may attribute to the risk of declining semen quality and hence protective role for antioxidant enzymes against the oxidative damage cannot be ruled out.