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Background: Ozone exposure could increase lung damage induced by airborne particulate matter. Particulate matter lung toxicity has been attributed to its metallic content. Aim: To evaluate the acute effect of intratracheal administration of copper sulfate (CuSO4) on rat lungs previously damaged by a chronic intermittent ozone exposure. Material and Methods: Two-months-old male Sprague-Dawley rats were exposed to 0.5 ppm ozone four h per day, five days a week, during two months. CuSO4 was intratracheally instilled 20 h after ozone exposure. Controls breathed filtered air or were instilled with 0.9% NaCl or with CuSO4 or were only exposed to ozone. We evaluated lung histopathology. F2 isoprostanes were determined in plasma. Cell count, total proteins, γ glutamyl-transpeptidase (GGT) and alkaline phosphatases (AP) were determined in bronchoalveolar lavage fluid (BALF). Results: Ozone increased total cell count, macrophages, proteins and AP in BALF (p < 0.05), and induced pulmonary neutrophil inflammation. CuSO4 plus air increased plasma F2 isoprostane levels and total cell count, neutrophils and proteins in BALF (p < 0.05). Histopathology showed foamy macrophages. Ozone plus CuSO4 exposed animals showed a neutrophil inflammatory lung response and an increase in total cell count, proteins, GGT and AP in BALF (p < 0.05). Foamy and pigmented alveolar macrophages were detected in all lungs of these animals (p < 0.001). Conclusions: Intratracheal instillation of a single dose of CuSO4 in rats previously subjected to a chronic and intermittent exposure to ozone induces a neutrophil pulmonary inflammatory response and cytoplasmic damage in macrophages.
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Animals , Male , Rats , Ozone/toxicity , Pneumonia/prevention & control , Copper Sulfate/administration & dosage , Pneumonia/chemically induced , Pneumonia/pathology , Time Factors , Rats, Sprague-Dawley , Models, Animal , Disease Models, Animal , Particulate Matter/toxicity , Lung/pathologyABSTRACT
Aims: Glutamate cysteine ligase (GCL) enzyme is involved in the synthesis of glutathione, which functions as an antioxidant. Polymorphisms in the sequence of amino acids making up the gene GCLC will cause differences in enzyme expression and GCLC activity. Gene expression that is influenced by oxidative stress can be used to measure markers such as F2-isoprostanes. This study aims to examine the association between the polymorphism in the GCLC gene with glutathione plasma level and F2-isoprostanes in contacts of person with infectious tuberculosis (TB). Methodology and results: Samples are taken from the family members of pulmonary TB patients who seeks treatment at the Pulmonary Centre (Lung Health Center for Public = BBKPM) and Policlinic of Dr Wahidin Sudirohusodo Hospital, Makassar. Total of approximately 4 mL of venous blood are taken from each person with pulmonary TB contacts and furtherly analyzed using genomic PCR-RFLP method and ELISA. Our results described that contacts of person with infectious TB for approximately 6 months have polymorphism C/C genotype at 80.3%, C/T of 18.3% and T/T for 1.4% of the total 71 samples with high levels of glutathione from 0.167 to 0.548 mM/mL and F2-isoprostanes level 72.4 - 1343.9 pg/mL. Conclusion, significance and impact of study: There are no significant association between GCLC gene polymorphism with glutathione and F2-isoprostanes levels of individual who had contacted infection TB. In this study the elevation of F2-isoprostanes equal to the decrease levels of glutathione.
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Glutamate-Cysteine LigaseABSTRACT
Objective To observe the effect of continuous positive airway pressure ventilation on hypersensitive C reaction protein (hsCRP) and 8-isoprostane in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).Methods A total of 78 OSAHS patients were enrolled and monitored by polysomnography (PSG) in January to March,2013.Another 40 healthy persons were chosen as controls during the same time.According to apnea hypopnea index(AHI) and oxygen saturation,the patients were divided into mild,moderate and severe groups.Blood and urinary 8-isoprostane and hsCRP levels were detected before and after monitoring.After continuous positive airway pressure treatment for three months,blood and urinary 8-isoprostane and hsCRP were also detected in three groups.Results (1) In OSAHS patients,blood 8-isoprostane levels before and after sleep monitoring were (273.80 ± 55.83)ng/L and (337.18 ± 56.28) ng/L urinary 8-isoprostane (35.65 ± 7.08) ng/L and (48.30 ± 14.17) ng/L,hsCRP (7.63 ± 6.10) μg/L and (9.68 ± 8.55) μg/L,respectively.Each parameter reached a significant difference before and after sleep(P ＜ 0.05).(2) The levels of blood CRP and urinary 8-isoprostane in the control group before sleep were (4.56 ± 2.43) μg/L,(264.14 ± 33.61) ng/L,(32.77 ± 9.61) ng/L,after sleep were (4.33 ± 2.08) μg/L,(284.27 ± 47.51) ng/L,(31.13 ± 8.24) ng/L.All the levels were less than those of OSAHS group (P ＜ 0.05).(3) The levels of blood 8-isoprostane in mild,moderate and severe groups after monitoring were (308.16 ± 53.48) ng/L,(327.36 ± 59.05) ng/L,(340.39 ± 55.31) ng/Lrespectively,and urinary 8-isoprostane were (35.23 ± 11.28) ng/L,(38.30 ± 10.89) ng/L,(44.57 ±12.69) ng/L,hsCRP were (5.63 ± 4.26) μg/L,(6.96 ± 4.43) μg/L,(8.92 ± 7.84) μg/L.None of these three parameters showed significant difference between the three groups (P ＞ 0.05).However,compared with the control group,blood and urine 8-isoprostane and hsCRP levels of any groups had significant differences(all P values ＜ 0.05).(3) There was no significant difference in the levels of hsCRP and 8-isoprostane after sleep between the three groups in OSAHS (P ＞ 0.05).(4) Urinary 8-isoprostane level after PSG was positively correlated with hsCRP (r =0.498,P ＜0.01).Either 8-isoprostane or hsCRP level was correlated with AHI (r =0.479,r =0.550;P ＜ 0.01).8-isoprostane and hsCRP levels were positively correlated with time of blood hemoglobin oxygen saturation below 90％ (r =0.413,r =0.502;P ＜ 0.01).(5) After continuous positive airway pressure treatment,the levels of 8-isoprostane and hsCRP both in blood or urine were decreased in the three groups of OSAHS patients (P ＜ 0.05).Conclusions Long term intermittent hypoxia in patients with OSAHS results in enhanced oxidative stress reaction and over-generated inflammatory mediators.There is a positive correlation between oxidative stress and inflammatory mediators,which promotes each other,leading to the organ dysfunction induced by hypoxia.
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Objective To investigate the relationship between the level of 8-iso-prostaglandin (8-iso-PG)F2αand the neural functional deficit in patients with acute cerebral infarction (ACI). Methods Sixty-seven ACI patients were se-lected in Neurological Department of Ganyu People’s Hospital. According to the age, these subjects were divided into two groups:the old group (≥60 years, n=37) and middle-young group (<60 years, n=30). Thirty healthy subjects were selected as controls (≥60 years). The age, gender and anamnesis were matched in two groups of elderly people. The ELISA was used to detect the plasma levels of 8-iso-PGF2αin two groups of patients. And NIHSS score was used to evaluate the severity of clinical neurological deficit. Results The plasma levels of 8-iso-PGF2α were significantly higher in old ACI group (506.38±138.63) ng/L than those of middle-young ACI group (420.18±132.72) ng/L and old control group (369.98±99.81) ng/L. There was no significant difference in plasma level of 8-iso-PGF2αbetween middle-young ACI group and old control group (F=9.272,P<0.05). The NIHSS score was significantly higher in old group (19.78±3.66) than that of middle-young group (17.73 ± 2.70, t=2.539,P<0.05). There was a positive correlation between plasma 8-iso-PGF2α level and NIHSS score in old group (r=0.504,P=0.001). Conclusion The oxidative stress plays an important role in the occurrence and de-velopment process of ACI in elderly patients. The earlier and reasonable antioxidant therapy plays a positive role to alleviate the clinical symptoms and promote the recovery of illness.
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Objective To investigate the level change of glucose excursion , 8-iso prostaglandin F 2α( 8-iso-PGF2α) in type 2 diabetes mellitus(T2DM), and its effects on nonalcoholic fatty liver disease (NAFLD).Methods A total of 62 inpatients with type 2 diabetes mellitus including T2DM group(DM, 30 cases) and T2DM with NAFLD group(DM+NAFLD, 32 cases) were recruited from October 2012 to November 2013 , normal glucose tolerance group had normal glucose tolerance ( NGT;30 cases ) with normal physical examination results.The age, gender, duration, blood pressure, body mass index (BMI), and blood lipid among three groups were no statistical difference .The clinical data of each patient were collected by professional people .Blood lipids and glycated hemoglobin (HbA1c) were detected.Oral glucose tolerance test (OGTT) were taken in all groups.The Postprandial glucose excursion (PPGE), blood glucose standard deviation (SDBG), mean blood glucose and (MBG) and HbA1c were used to evaluate the glucose excursion.Serum 8-iso-PGF2αwas detected by enzyme-linked immunosorbent (ELISA) to evaluate oxidative stress.Inter-group com-parison was conducted with analysis of variance ( ANOVA) .Correlation analysis was used to evaluate the factors of influence .Results⑴The levels of PPGE[(7.34 ±2.23) mmol/L vs (8.52 ±2.43) mmol/L],SDBG[(2.43 ±0.90) mmol/L vs (2.80 ±0.78) mmol/L], MBG[(11.06 ±1.76) mmol/L vs (13.65 ±2.83) mmol/L], and HbA1c [(7.59 ±1.02)% vs (8.05 ±1.52)%] in T2DM group and T2DM with NAFLD group were significantly higher than that in NGT group (both P <0.05); and that in NAFLD group have significantly rise than that in DM group ( P <0.05), but there was no significant difference in HbA 1c between groups.⑵ The level of serum 8-iso-PGF2αwas gradually increased from NGT group [(33.45 ±8.60) pg/ml], DM group [(47.33 ±15.30) pg/ml], to DM +NAFLD group [(56.07 ±13.10) pg/ml], with statistically significant difference ( P <0.05);⑶The Person corre-lation analysis showed that the content of serum 8-iso-PGF2αwas positively correlated with PPGE, SDBG, and MBG ( r =0.796, 0.778 , 0.712 , P <0.01 ) .Conclusions Serum 8-iso-PGF2αis a better parameter to reflect the status of body oxidative stress .The level of oxidative stress is increased with the increase of glucose excursion in T 2DM, which is the important mechanism of its complica-tions of NAFLD.
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Reactive oxygen species have emerged as important molecules in cardiovascular function. Recent research has shown that the NADPH oxidases are important sources of superoxide in vascular cells and myocytes. The NADPH oxidases vascular share some, but not all, of the characteristics of the enzyme in neutrophils, both produce superoxide, which is metabolized to hydrogen peroxide, at the same time these reactive oxygen species serve as second messengers activate multiple intracellular signalling pathways. NADPH oxidases are essential in the physiological response of vascular cellsto pathological states such as atherosclerosis, and are functionally relevant in activation and recruitment of platelets. Recent studies suggest a key role for NADPH oxidase in the formation of a specific product from the oxidation of arachidonic acid, and a potential role in the process of recruitment of platelets. Taking into account these characteristics and evidence of the involvement of the NADPH oxidases in cardiovascular diseases as the thrombosis, inhibition of this enzymatic system appears as a promising therapy to treat and prevent these diseases.
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Humans , Atherosclerosis/enzymology , Reactive Oxygen Species , NADPH Oxidases/metabolism , Blood Platelets/enzymology , Platelet Activation/physiology , Antioxidants , Isoprostanes , PolyphenolsABSTRACT
Isoprostanes are endogenously formed products of lipid peroxidation,furthermore,they are undependent on ring oxidase and lipoxygenase.lsoprostanes are established markers of oxidative stress.Furthermore,they are markers of oxidative stress and independent risk markers of coronary heart disease.Studies have indicated that oxidative stress is one of the reasons for the pathological changes of Coronary artery.8-Iso-prostaglandin F( 2 ),which is the maximum in isoprostanes,belongs to the unsaturated fatty acid (20),exists in the phospholipid SN-2 position.8-1so-prostaglandin F ( 2 ),a representative isoprostane,is a specific,sensitive,reliable biomarker for enhanced oxidant stress in vivo,which plays an important role in coronary lesions.
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ObjectiveTo determine the levels of 8-iso-prostaglandin F2α (PGF2α) in sera and lesions as well as antioxidant capacity in sera of psoriatic patients,and to assess their correlations with disease severity.MethodsSerum and skin tissue samples were collected from 15 healthy controlsand 50 patients with psoriasis vulgaris.Spectrophotometry was performed to determine the levels of total antioxidant capacity (T-AOC) and the activities of antioxidant enzymes such as superoxide dismutase (SOD),catalase (CAT) and glutathione peroxidase (GSH-Px) in serum samples.Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical SP method were carried out to detect the expression level of 8-iso-PGF2α in the serum and tissue specimens respectively.ResultsThe psoriatic patients showed a significant decrease in the serum level of TAOC((12.78 ± 7.75) U/ml vs. (23.17 ± 8.81) U/ml,P＜ 0.01) as well as the activities of SOD((28.91 ±9.35) U/ml vs.(51.36 ± 7.92) U/ml,P＜ 0.01) and GSH-Px ((180.64 ± 47.70) U vs.(244.20 ± 66.68) U,P ＜ 0.01 ) compared with the healthy controls.The serum T-AOC level and SOD activity were lower in patients with severe psoriasis than those with mild or moderate psoriasis ((9.06 ± 5.30) U/ml vs. (15.27 ± 8.18) U/ml,(21.63 ± 5.28) U/ml vs. (33.76 ± 8.28) U/ml,both P＜ 0.01 ),while there was no significant difference in the activity of GSH-Px between patients with severe and mild or moderate psoriasis.The serum CAT activity was significantly higher in patients with mild or moderate psoriasis than in the healthy controls and patients with severe psoriasis ( (36.92 ± 11.31 ) U/ml vs.( 28.55 ± 8.51 ) U/ml and (24.15 ± 9.36 ) U/ml,P ＜ 0.05 and 0.01 ).Increased serum and lesional 8-iso-PGF2α levels were observed in psoriatic patients compared with the healthy controls ( (88.77 ± 25.27) ng/L vs.(38.34 ± 8.94) ng/L,0.0186 ± 0.0082 vs.0.0027 ± 0.0014,both P ＜ 0.01),as well as in patients with severe psoriasis compared with those with mild or moderate psoriasis(( 114.24 ±13.93) ng/L vs.(71.78 ± 14.35) ng/L,0.0279 ± 0.0027 vs.0.0125 ± 0.0030,both P＜ 0.01 ).The psoriasis area and severity index(PASI) score was negatively correlated with T-AOC level,SOD and CAT activities(r =-0.384,-0.573 and -0.444,all P ＜ 0.01 ),positively correlated with serum and lesional 8-iso-PGF2α levels (r =0.710,0.783,both P ＜ 0.01 ),and uncorrelated with GSH-Px activity.None of the parameters was correlated with the course of disease.ConclusionThe serum and lesional levels of 8-iso-PGF2α may be a more sensitive marker for oxidative damage and disease severity.
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Objectives To evaluate the effect of N-Acetylcysteine on the airway inflammation and remodeling of obese asthma mice with high-fat diets. Methods Forty female C57BL/6J mice were randomly divided into 4 groups, asthma group (A), obese asthma group (B), treatment group (C) and normal control group (D). Group A were sensitized and challenged by ovalbum (OVA) and normal diets. Group B were sensitized and challenged as group A but fed with high-fat diets, while group C were sensitized, challenged and fed as group B, but administrated N-Acetylcysteine 200 mg/kg. d from the third week after challenge. The cells in BALF were counted and classified after staining, IL-6 and 8-iso-PGF2α(8-iso-PGF2α) in lung tissues were detected by ELISA. WAt, WAm, Pbm, as the remodeling indices, measured in lung pathological section. All parameters were compared among 4 groups. Results In comparison with group D, the leukocytes and EOS in BALF, WAt/Pbm, WAm/Pbm in lung section were increased as well as IL-6 and 8-iso-PGF2α in lung tissue elevated in group A and group B, while the maximum changes were observed in group B (P ＜0. 05). After NAC treatment, the IL-6, 8-iso-PGF2α and WAt/ Pbm were decreased significantly (P ＜0. 05). Pearson correlation analysis showed that WAt/Pbm and IL-6 were in positive correlation with 8-iso-PGF2α (r =0. 817, 0. 737, P ＜0. 01). Conclusions N-Acetylcysteine can alleviate the airway inflammation and remodel reaction of asthma by a substantial inhibition of the oxidative stress reaction in lung.
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ObjectiveTo investigate the role of 15-F2t-isoprostane in intestinal injury induced by intestinal ischemia/reperfusion (I/R) in rats.MethodsThirty-two pathogen free adult male SD rats weighing 230-255 g were randomly divided into 4 groups ( n =8 each):group sham operation (group S) ; group intestinal I/R; group SQ-29548 (TXA2 receptor antagonist) (group SQ) and group DMSO (the solvent).Intestinal I/R was induced by 60 min occlusion of superior mesenteric artery (SMA) followed by 120 main reperfusion in groups I/R,SQ and DMSO SQ-29548 2 μmol/kg and DMSO were injected subcutaneusly at abdominal wall at 30 min before SMS in groups SQ and DMSO respectively.Arterial blood samples were taken at 120 min of reperfusion for determination of serum diamine oxidase (DAO) activity and 15-F2t-isoprostane,endothelin-1 (ET-1) and thromboxane B2 (TXB2) concentrations.Intestinal tissues were removed for microscopic examination and determination of myeloperoxidase (MPO) and SOD activities,MDA and lactate contents.Intestinal damage was assessed and scored according to Chiu (0 =normal,5 =disruption of tunica propria,bleeding and ulceration).ResultsIntestinal I/R significantly increased Chiu's score,MDA and lactate contents and MPO activity and decreased SOD activity in intestine in group I/R as compared with group S.SQ-29548 pretreatment significantly decreased Chiu's score,lactate content and MPO activity in intestine and increased intestinal SOD activity and decreased serum DAO activity and ET-1 concentration in group SQ as compared with group I/R.Conclusion15-F2t-isoprostane is involved in the development of intestinal injury induced by intestinal I/R by activating TXA2 receptor,increasing ET-1 production and promoting neutrophil infiltration.
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Objective To investigate the impact of smoking on the level of urinary 8-iso prostaglandin (PG) F2? (8-iso-PGF2?) of patients with acute cerebral infarction. 8-iso-PGF2? is a product of arachidonic acid catalyzed by free-radical, and it has been identified as an indicator of oxidative stress in vivo during reperfusion. Methods Plasma and urine samples were obtained from 28 patients with acute cerebral infarction. Among them 14 patients with no smoking habit were chosen as control group according to the selection criterion, and the other 14 patients with smoking habit were chosen as investigation group according to the same criterion. There was no significant difference between the two groups in age, gender ratio, blood pressure, lipids level, blood glucose, focus location, and degree of the cerebral focus of infaration. The concentration of urinary 8-iso PGF2? and levels of low-density lipoproteins (LDL), total cholesterol, LDL-triglyceride (TG) and LDL-free cholesterol in plasma were measured by enzyme immunoassay. The quantification of urinary 8-iso PGF2? and LDL levels in plasma were performed for each sample respectively. Results The concentration of urinary 8-epi PGF2? of the patients with smoking habit was significantly higher than that in the patients of control group (75.79?10.76 vs 67.36?9.18 ng/mmol creatinine, P0.05, respectively) between the two groups. Conclusions Cigarette smoking may raise the urinary 8-iso-PGF2? level of patients with acute cerebral infarction, suggesting an increase in the level of oxidative stress in vivo in these subjects.
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Objective To investigate the preventive effects of midazolam and propofol on liver against hypoxia/reoxgenation(H/R) injury in rats.Methods Twenty-four Wistar rats of both sexes weighing 200-250g were randomized into four groups:control group(group A),hypoxia/reoxygenation(group B),H/R + midazolam(group C) and H/R + propofol(group D).The 8-iso-prostaglandin F2?(8-iso-PGF2?) levels in the hepatic tissue were determined by enzyme-linked immunosorbent assay(ELISA).The contents of nitric oxide(NO) and the activity of nitric-oxide synthase(NOS) in hepatic tissue were determined by biochemistry methods.Results After hypoxia and reoxgenation injury in rats,the 8-iso-PGF2? level of hepatic tissue in group B was significantly higher than that in group A(P
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Objective To explore the effects of oxidative stress in the pathogenesis of lung injury and observe the influence of N-acetylcysteine (NAC). Methods The lung histopathology was observed by light microscope. The level of 8-iso-prostaglandin F2?lpha (8-iso-PGF2?) in blood plasm were measured by ELISA. The difference of 8-iso-PGF2? in blood plasm in air group, different dose NAC groups between hyperoxia-model and the air group was compared. Results In hyperoxia-model group, the inequality of size of lung alveoli, hemorrhage and inflammatory cell infiltration in lung alveoli were observed on the 3rd and 7th day. The alveolar septum was thick in the hyperoxic-damaged lungs on the 14th and the 21st day. In hyperoxia+high-dose NAC group, very small amounts of red blood cells leaked out into alveoli on the 3rd and 7th day and alveolar septum had no thickening obviously on the 14th day and the 21st day. The level of 8-iso-PGF2? in blood plasm in hyperoxia-model group [(28.33?5.57) pg/ml, (51.21?15.01) pg/ml, (84.54?14.85) pg/ml and (43.14?11.37) pg/ml at every time points] was higher than that of the air group and hyperoxia+high-dose NAC group(P