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Keyser BM. Cytotoxicity, oxidative stress, and inflammatory response of smokeless tobacco extracts and cytotoxicity of combustible cigarette whole smoke in a 3D oral organotypic buccal cell model. Toxicol Mech Methods 2022; 32:352-361. [PMID: 34923904 DOI: 10.1080/15376516.2021.2009949] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 11/18/2021] [Accepted: 11/18/2021] [Indexed: 10/19/2022]
Abstract
Oral disease is frequently associated with viral and environmental exposures and oral hygiene. The use of tobacco is a risk factor in the development of oral disease. Cytotoxicity, inflammatory response, and oxidative stress have been reported to have a role in the development of oral disease. These three endpoints were evaluated in a 3D human oral buccal model, EpiOral™, following exposure to CORESTA reference smokeless tobacco products (CRPs) and cigarette whole smoke. CRPs for Swedish style snus (CRP1), moist snuff (CRP2), and dry snuff (CRP3) were each extracted in complete artificial saliva (CAS) with a ratio of 300 mg CRP to 1 mL of CAS. Each of the CRP extracts (15-300 mg/ml) were applied to the apical side of a 3D organotypic buccal cell model for 24 or 48 h continuously, then cytotoxicity (LDH), oxidative stress (8-isoprostane), and inflammatory response (IP10, IL-1α, and IL-8) were measured. Experiments with 3R4F cigarettes were conducted by exposing the buccal tissues to whole smoke for a maximum of 2.5 h. Cytotoxicity (MTT) was measured 24 h post-exposure. Exposure of buccal tissues to whole smoke from a cigarette induced a dose-dependent cytotoxic response. In contrast, the CRP extracts elicited minimal cytotoxicity (<15%) when compared to CAS (vehicle control), but time- and dose-dependent effects on oxidative stress and inflammatory response were observed. Collectively, these data demonstrate that a 3D organotypic buccal human model may be used to assess biological mechanisms (MOAs) involved in the development of oral disease following exposure to smokeless tobacco products and may be applicable for differentiation between tobacco product categories.
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Affiliation(s)
- Brian M Keyser
- Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC, USA
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Duchene B, Caffry S, Kaminsky DA, Que LG, Poynter ME, Dixon AE. Functional significance of 8-isoprostanes in sinonasal disease and asthma. Respir Med 2021; 185:106506. [PMID: 34166960 PMCID: PMC9531183 DOI: 10.1016/j.rmed.2021.106506] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/19/2021] [Accepted: 06/05/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND The purpose of this study was to investigate how 8-isoprostanes, used as a marker of airway oxidative stress, were related to sinus disease and asthma. METHODS We analyzed samples and data from two separate studies, one investigating sinonasal disease in asthma, the other investigating the effect of BMI on airway disease. We measured airway (nasal lavage) 8-isoprostanes and investigated the relationship with measures of sinus and asthma symptoms, asthma control and lung function. RESULTS The study of people with sinonasal disease and poorly controlled asthma included 48 obese, 31 overweight and 23 lean participants. In multivariate analysis, nasal lavage 8-isoprostane levels increased with increasing BMI (p < 0.01), and were higher in Caucasian than African American participants (p = 0.01). Sinus symptoms were inversely related to nasal 8-isoprostanes (p = 0.02) independent of BMI and Race. In the study investigating the effect of BMI on airway disease, we enrolled 13 controls with obesity and 21 people with obesity and asthma: 8-isoprostane levels were higher in obese controls than in obese people with asthma (p < 0.01), and levels were inversely related to sinus symptoms (p = 0.02) and asthma control (p < 0.01). INTERPRETATION 8-isoprostanes in nasal lavage are increased in obesity, and increased in Caucasians compared with African Americans. However, levels are higher in obese controls than obese people with asthma, and appear inversely related to symptoms of airway disease. CLINICAL IMPLICATION Airway 8-isoprostanes likely reflect complex oxidative signaling pathways, which are altered in obesity and those of different race, rather than being a simple marker of airway oxidative injury. CAPSULE SUMMARY Increased airway oxidative signaling (8-isoprostanes), may reflect normal physiology in the setting of obesity, as decreased levels are associated with disease activity in people with chronic sinonasal disease and asthma.
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Affiliation(s)
- Brittany Duchene
- Larner College of Medicine, University of Vermont, Burlington, VT, USA
| | - Sarah Caffry
- Larner College of Medicine, University of Vermont, Burlington, VT, USA
| | - David A Kaminsky
- Larner College of Medicine, University of Vermont, Burlington, VT, USA
| | | | - Matthew E Poynter
- Larner College of Medicine, University of Vermont, Burlington, VT, USA
| | - Anne E Dixon
- Larner College of Medicine, University of Vermont, Burlington, VT, USA.
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Menzel A, Samouda H, Dohet F, Loap S, Ellulu MS, Bohn T. Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice-Which to Use Regarding Disease Outcomes? Antioxidants (Basel) 2021; 10:antiox10030414. [PMID: 33803155 PMCID: PMC8001241 DOI: 10.3390/antiox10030414] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 03/03/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023] Open
Abstract
Many chronic conditions such as cancer, chronic obstructive pulmonary disease, type-2 diabetes, obesity, peripheral/coronary artery disease and auto-immune diseases are associated with low-grade inflammation. Closely related to inflammation is oxidative stress (OS), which can be either causal or secondary to inflammation. While a low level of OS is physiological, chronically increased OS is deleterious. Therefore, valid biomarkers of these signalling pathways may enable detection and following progression of OS/inflammation as well as to evaluate treatment efficacy. Such biomarkers should be stable and obtainable through non-invasive methods and their determination should be affordable and easy. The most frequently used inflammatory markers include acute-phase proteins, essentially CRP, serum amyloid A, fibrinogen and procalcitonin, and cytokines, predominantly TNFα, interleukins 1β, 6, 8, 10 and 12 and their receptors and IFNγ. Some cytokines appear to be disease-specific. Conversely, OS-being ubiquitous-and its biomarkers appear less disease or tissue-specific. These include lipid peroxidation products, e.g., F2-isoprostanes and malondialdehyde, DNA breakdown products (e.g., 8-OH-dG), protein adducts (e.g., carbonylated proteins), or antioxidant status. More novel markers include also -omics related ones, as well as non-invasive, questionnaire-based measures, such as the dietary inflammatory-index (DII), but their link to biological responses may be variable. Nevertheless, many of these markers have been clearly related to a number of diseases. However, their use in clinical practice is often limited, due to lacking analytical or clinical validation, or technical challenges. In this review, we strive to highlight frequently employed and useful markers of inflammation-related OS, including novel promising markers.
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Affiliation(s)
- Alain Menzel
- Laboratoires Réunis, 38, Rue Hiehl, L-6131 Junglinster, Luxembourg; (A.M.); (F.D.)
| | - Hanen Samouda
- Nutrition and Health Research Group, Department of Population Health, Luxembourg Institute of Health, 1 A-B, Rue Thomas Edison, L-1445 Strassen, Luxembourg;
| | - Francois Dohet
- Laboratoires Réunis, 38, Rue Hiehl, L-6131 Junglinster, Luxembourg; (A.M.); (F.D.)
| | - Suva Loap
- Clinic Cryo Esthetic, 11 Rue Éblé, 75007 Paris, France;
| | - Mohammed S. Ellulu
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Al-Azhar University of Gaza (AUG), Gaza City 00970, Palestine;
| | - Torsten Bohn
- Nutrition and Health Research Group, Department of Population Health, Luxembourg Institute of Health, 1 A-B, Rue Thomas Edison, L-1445 Strassen, Luxembourg;
- Correspondence:
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Influence of smoking on levels of urinary 8-iso Prostaglandin F2α. Toxicol Rep 2018; 6:18-25. [PMID: 30519530 PMCID: PMC6260378 DOI: 10.1016/j.toxrep.2018.11.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 10/15/2018] [Accepted: 11/19/2018] [Indexed: 11/21/2022] Open
Abstract
Cigarette smoking is an important modifiable risk factor for cardiovascular disease. Cigarette smoking affects oxidative stress markers such as 8-iso prostaglandin F2α. The effect of smoking on urinary 8-iso prostaglandin F2α levels was meta-analyzed. Urinary 8-iso prostaglandin F2α levels were increased in smokers. Background To evaluate the reduced-risk potential of alternative tobacco products, biomarkers that are involved in the biological pathways affected by cigarette smoking and smoking cessation are needed. Isoprostanes, a measure of oxidative stress, appear to be influenced by smoking and reversible upon smoking cessation and therefore could be a good biomarker. This review aims at quantifying the effect of smoking and smoking cessation on levels of urinary 8-iso prostaglandin F2α (8-epi-PGF2α), an isoprostane. Methods PubMed and Scopus databases were searched for publications that reported 8-epi-PGF2α levels in smokers and nonsmokers as well as articles reporting the effect of smoking cessation on 8-epi-PGF2α levels. Results Eighteen studies assessing 8-epi-PGF2α levels by smoking status were identified. Five of the papers reported the results as quantity excreted in 24-hour urine (μg/24 h), and 15 reported creatinine adjusted values. The meta-analyses show increased levels of 8-epi-PGF2α in current smokers compared with nonsmokers (mean difference = 0.16, 95% confidence interval [95%CI]: 0.14–0.19 μg/24 h with inconsistency statistic [I2] = 98%; mean difference = 172.38, 95%CI: 152.75–192.01 pg/mg creatinine with I2 = 89%, respectively). There were too few publications to perform a meta-analysis assessing the effects of smoking cessation on 8-epi-PGF2α levels. Conclusions Due to the high heterogeneity among the studies included in these meta-analyses, it is difficult to generalize the results; however, our study indicates increased levels of 8-epi-PGF2α and therefore increased oxidative stress in smokers compared with nonsmokers. More studies are still needed to assess if 8-epi-PGF2α levels are reversible after cessation.
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Suitability of biomarkers of biological effects (BOBEs) for assessing the likelihood of reducing the tobacco related disease risk by new and innovative tobacco products: A literature review. Regul Toxicol Pharmacol 2018; 94:203-233. [DOI: 10.1016/j.yrtph.2018.02.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 02/04/2018] [Accepted: 02/05/2018] [Indexed: 02/07/2023]
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van 't Erve TJ, Kadiiska MB, London SJ, Mason RP. Classifying oxidative stress by F 2-isoprostane levels across human diseases: A meta-analysis. Redox Biol 2017; 12:582-599. [PMID: 28391180 PMCID: PMC5384299 DOI: 10.1016/j.redox.2017.03.024] [Citation(s) in RCA: 133] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/23/2017] [Accepted: 03/24/2017] [Indexed: 02/07/2023] Open
Abstract
The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures. In this meta-analysis, the F2-isoprostane, 8-iso-PGF2α, was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges’ g) in 8-iso-PGF2α levels between affected and control populations were calculated. The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF2α levels (g<0.8) were found in the following conditions: hypertension (g=0.4), metabolic syndrome (g=0.5), asthma (g=0.4), and tobacco smoking (g=0.7). In contrast, large increases in 8-iso-PGF2α levels were observed in pathologies of the kidney, e.g., chronic renal insufficiency (g=1.9), obstructive sleep apnoea (g=1.1), and pre-eclampsia (g=1.1), as well as respiratory tract disorders, e.g., cystic fibrosis (g=2.3). In conclusion, we have established a quantitative classification for the level of 8-iso-PGF2α generation in different human pathologies and exposures based on a comprehensive meta-analysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation.
Oxidative damage is highly variable in human conditions as measured by F2-isoprostanes. Respiratory tract and urogenital diseases have the highest F2-isoprostanes. Cancer and cardiovascular diseases have surprisingly low F2-isoprostanes.
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Affiliation(s)
- Thomas J van 't Erve
- Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA.
| | - Maria B Kadiiska
- Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA
| | - Stephanie J London
- Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA; Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA
| | - Ronald P Mason
- Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA
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Masiá M, Padilla S, Fernández M, Rodríguez C, Moreno A, Oteo JA, Antela A, Moreno S, del Amo J, Gutiérrez F, CoRIS, Biobanco. Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients. PLoS One 2016; 11:e0153456. [PMID: 27111769 PMCID: PMC4844170 DOI: 10.1371/journal.pone.0153456] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Accepted: 03/30/2016] [Indexed: 01/07/2023] Open
Abstract
Objective We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients. Methods We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement. Results 54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23–4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log10 increase, 2.05 [0.91–4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log10 increase, 1.39 (1.01–1.91), P = 0.043; and OR (95% CI) per 1 log10 increase, 1.46 (1.07–1.99), P = 0.014, respectively, when adjustment included F2-IsoPs and MDA. Conclusion Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation.
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Affiliation(s)
- Mar Masiá
- Infectious Diseases Unit, Hospital General de Elche, Universidad Miguel Hernández, Alicante, Spain
| | - Sergio Padilla
- Infectious Diseases Unit, Hospital General de Elche, Universidad Miguel Hernández, Alicante, Spain
| | - Marta Fernández
- Infectious Diseases Research Laboratory, Hospital General de Elche, Alicante, Spain
| | - Carmen Rodríguez
- HIV/AIDS and Sexually Transmitted Diseases Clinic, Centro Sanitario Sandoval, Madrid, Spain
| | - Ana Moreno
- Infectious Diseases Service, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain
| | - Jose A. Oteo
- Infectious Diseases Service, Hospital San Pedro de La Rioja, Logroño, Spain
| | - Antonio Antela
- Infectious Diseases Unit, Hospital Clínico de Santiago, La Coruña, Spain
| | - Santiago Moreno
- Infectious Diseases Service, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain
| | - Julia del Amo
- Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain
| | - Félix Gutiérrez
- Infectious Diseases Unit, Hospital General de Elche, Universidad Miguel Hernández, Alicante, Spain
- * E-mail:
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Asombang AW, Kayamba V, Lisulo MM, Trinkaus K, Mudenda V, Sinkala E, Mwanamakondo S, Banda T, Soko R, Kelly P. Esophageal squamous cell cancer in a highly endemic region. World J Gastroenterol 2016; 22:2811-2817. [PMID: 26973419 PMCID: PMC4778003 DOI: 10.3748/wjg.v22.i9.2811] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Revised: 12/21/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α (8-isoPGF2α).
METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence of esophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus (HIV) serology. Urine was collected, and 8-isoPGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine.
RESULTS: Forty five controls (mean age 54.2 ± 15.3, 31 male) and 27 cases (mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases (median 16.8) than controls (median 23.2), P = 0.01. Histopathologically, 25/27 (93%) were squamous cell carcinoma and 2/27 (7%) adenocarcinoma. More cases smoked cigarettes (OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly (P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups (P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases (0.03 ng/mg creatinine) than controls (0.01 ng/mg creatinine) (OR = 2.35, 95%CI: 1.19-4.65, P = 0.014).
CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not.
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Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles. Part Fibre Toxicol 2013; 10:14. [PMID: 23587270 PMCID: PMC3641025 DOI: 10.1186/1743-8977-10-14] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 04/12/2013] [Indexed: 01/10/2023] Open
Abstract
Background Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear. Methods To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin–induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter. Results DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice. Conclusion This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.
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Eder A, Koegl E, von Duvillard SP, Sinzinger H, Berent R. Influence of cigarette smoking on synthesis of eicosanoids, isoprostanes and lipoxygenase metabolites in apical periodontitis. Arch Oral Biol 2012; 57:1133-40. [PMID: 22682033 DOI: 10.1016/j.archoralbio.2012.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Revised: 05/07/2012] [Accepted: 05/10/2012] [Indexed: 01/15/2023]
Abstract
UNLABELLED Arachidonic acid (AA) is metabolized to eicosanoids and isoprostanes (IPs) via different pathways. The presence of granuloma in apical periodontitis (AP) is linked with inflammation and the synthesis of metabolites of AA. OBJECTIVE We investigated the conversion rate of (14)C labelled arachidonic acid ((14)C-AA), the lipoxygenases (LOX) products and the endogenous synthesis of eicosanoids and IPs in extracted granuloma. Furthermore, we assessed if there are markers for bone destruction and the influence of cigarette smoking. PATIENTS AND METHODS In 46 patients with symptoms and corresponding radiological signs of AP, teeth were extracted including the periapical granuloma. The endogenous synthesis of eicosanoids and IPs, the conversion rate of (14)C-AA and LOX products in extracted granuloma were analyzed. RESULTS We found that smoking increases significantly the synthesis of IPs and LOX-metabolites in granuloma. Furthermore, smoking may have contributed to significant differences in qualitative and quantitative profile of eicosanoids, IPs and the conversion rate of (14)C-AA independent of the size of the granuloma. CONCLUSIONS Our data demonstrate that in smokers with granuloma due to AP products of lipid peroxidation as 8-iso-PGF(2α) and products of the LOX-pathway are increased at the expense of cyclooxygenase products. The size of granuloma did not influence the amount of synthesized eicosanoids, IPs or LOX-metabolites out of (14)C-AA whereas cigarette smoking was a significantly influencing and modifiable risk factor.
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Affiliation(s)
- Andreas Eder
- Department for Conservative Dentistry, University Dental Medical School Vienna, Austria
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Capra V, Bäck M, Barbieri SS, Camera M, Tremoli E, Rovati GE. Eicosanoids and Their Drugs in Cardiovascular Diseases: Focus on Atherosclerosis and Stroke. Med Res Rev 2012; 33:364-438. [DOI: 10.1002/med.21251] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Valérie Capra
- Department of Pharmacological Sciences; University of Milan; Via Balzaretti 9 20133 Milan Italy
| | - Magnus Bäck
- Department of Cardiology and Center for Molecular Medicine; Karolinska University Hospital; Stockholm Sweden
| | | | - Marina Camera
- Department of Pharmacological Sciences; University of Milan; Via Balzaretti 9 20133 Milan Italy
- Centro Cardiologico Monzino; I.R.C.C.S Milan Italy
| | - Elena Tremoli
- Department of Pharmacological Sciences; University of Milan; Via Balzaretti 9 20133 Milan Italy
- Centro Cardiologico Monzino; I.R.C.C.S Milan Italy
| | - G. Enrico Rovati
- Department of Pharmacological Sciences; University of Milan; Via Balzaretti 9 20133 Milan Italy
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Miri R, Saadati H, Ardi P, Firuzi O. Alterations in oxidative stress biomarkers associated with mild hyperlipidemia and smoking. Food Chem Toxicol 2012; 50:920-6. [DOI: 10.1016/j.fct.2011.12.031] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Revised: 11/30/2011] [Accepted: 12/20/2011] [Indexed: 11/25/2022]
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Seet RCS, Lee CYJ, Loke WM, Huang SH, Huang H, Looi WF, Chew ES, Quek AML, Lim ECH, Halliwell B. Biomarkers of oxidative damage in cigarette smokers: which biomarkers might reflect acute versus chronic oxidative stress? Free Radic Biol Med 2011; 50:1787-93. [PMID: 21420490 DOI: 10.1016/j.freeradbiomed.2011.03.019] [Citation(s) in RCA: 110] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2011] [Revised: 02/28/2011] [Accepted: 03/11/2011] [Indexed: 11/17/2022]
Abstract
Cigarette smoking predisposes to the development of multiple diseases involving oxidative damage. We measured a range of oxidative damage biomarkers to understand which differ between smokers and nonsmokers and if the levels of these biomarkers change further during the act of smoking itself. Despite overnight abstinence from smoking, smokers had higher levels of plasma total and esterified F(2)-isoprostanes, hydroxyeicosatetraenoic acid products (HETEs), F(4)-neuroprostanes, 7-ketocholesterol, and 24- and 27-hydroxycholesterol. Levels of urinary F(2)-isoprostanes, HETEs, and 8-hydroxy-2'-deoxyguanosine were also increased compared with age-matched nonsmokers. Several biomarkers (plasma free F(2)-isoprostanes, allantoin, and 7β-hydroxycholesterol and urinary F(2)-isoprostane metabolites) were not elevated. The smokers were then asked to smoke a cigarette; this acute smoking elevated plasma and urinary F(2)-isoprostanes, plasma allantoin, and certain cholesterol oxidation products compared to presmoking levels, but not plasma HETEs or urinary 8-hydroxy-2'-deoxyguanosine. Smokers showed differences in plasma fatty acid composition. Our findings confirm that certain oxidative damage biomarkers are elevated in smokers even after a period of abstinence from smoking, whereas these plus some others are elevated after acute smoking. Thus, different biomarkers do not measure identical aspects of oxidative stress.
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Affiliation(s)
- Raymond C S Seet
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Balakrishna S, Saravia J, Thevenot P, Ahlert T, Lominiki S, Dellinger B, Cormier SA. Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs. Part Fibre Toxicol 2011; 8:11. [PMID: 21388553 PMCID: PMC3061909 DOI: 10.1186/1743-8977-8-11] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2010] [Accepted: 03/09/2011] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM). The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs), in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma. METHODS Neonatal rats (7-days of age) were exposed to EPFR-containing combustion generated ultrafine particles (CGUFP), non-EPFR containing CGUFP, or air for 20 minutes per day for one week. Pulmonary function was assessed in exposed rats and age matched controls. Lavage fluid was isolated and assayed for cellularity and cytokines and in vivo indicators of oxidative stress. Pulmonary histopathology and characterization of differential protein expression in lung homogenates was also performed. RESULTS Neonates exposed to EPFR-containing CGUFP developed significant pulmonary inflammation, and airway hyperreactivity. This correlated with increased levels of oxidative stress in the lungs. Using differential two-dimensional electrophoresis, we identified 16 differentially expressed proteins between control and CGUFP exposed groups. In the rats exposed to EPFR-containing CGUFP; peroxiredoxin-6, cofilin1, and annexin A8 were upregulated. CONCLUSIONS Exposure of neonates to EPFR-containing CGUFP induced pulmonary oxidative stress and lung dysfunction. This correlated with alterations in the expression of various proteins associated with the response to oxidative stress and the regulation of glucocorticoid receptor translocation in T lymphocytes.
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Affiliation(s)
- Shrilatha Balakrishna
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
- Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA
| | - Jordy Saravia
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
| | - Paul Thevenot
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
| | - Terry Ahlert
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
| | - Slawo Lominiki
- Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Barry Dellinger
- Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Stephania A Cormier
- Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
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15
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Halliwell B, Lee CYJ. Using isoprostanes as biomarkers of oxidative stress: some rarely considered issues. Antioxid Redox Signal 2010; 13:145-56. [PMID: 20001743 DOI: 10.1089/ars.2009.2934] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The measurement of F2-isoprostanes by methods utilizing mass spectrometry is widely regarded as the best currently available biomarker of lipid peroxidation. F2-isoprostanes and their metabolites can be measured accurately in plasma, urine, and other body fluids using mass spectrometric techniques, and detailed protocols have been published in several papers. However, many clinical studies and intervention studies with diets or supplements, have employed single "spot" measurements of F2-isoprostanes on either plasma/serum or urine to estimate "oxidative stress." This review examines the validity of the common assumption that plasma and urinary F2-isoprostane measurements are equivalent. It identifies scenarios where they may not be and where "spot" measurements can be misleading, with examples from the literature. We also discuss the controversial issue of whether and how F2-isoprostane levels in plasma should be standardized against lipids, and, if so, which lipids to use.
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Affiliation(s)
- Barry Halliwell
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore , Singapore
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16
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Warner JH, Liang Q, Sarkar M, Mendes PE, Roethig HJ. Adaptive regression modeling of biomarkers of potential harm in a population of U.S. adult cigarette smokers and nonsmokers. BMC Med Res Methodol 2010; 10:19. [PMID: 20233412 PMCID: PMC2846953 DOI: 10.1186/1471-2288-10-19] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2009] [Accepted: 03/16/2010] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This article describes the data mining analysis of a clinical exposure study of 3585 adult smokers and 1077 nonsmokers. The analysis focused on developing models for four biomarkers of potential harm (BOPH): white blood cell count (WBC), 24 h urine 8-epi-prostaglandin F2alpha (EPI8), 24 h urine 11-dehydro-thromboxane B2 (DEH11), and high-density lipoprotein cholesterol (HDL). METHODS Random Forest was used for initial variable selection and Multivariate Adaptive Regression Spline was used for developing the final statistical models RESULTS The analysis resulted in the generation of models that predict each of the BOPH as function of selected variables from the smokers and nonsmokers. The statistically significant variables in the models were: platelet count, hemoglobin, C-reactive protein, triglycerides, race and biomarkers of exposure to cigarette smoke for WBC (R-squared = 0.29); creatinine clearance, liver enzymes, weight, vitamin use and biomarkers of exposure for EPI8 (R-squared = 0.41); creatinine clearance, urine creatinine excretion, liver enzymes, use of Non-steroidal antiinflammatory drugs, vitamins and biomarkers of exposure for DEH11 (R-squared = 0.29); and triglycerides, weight, age, sex, alcohol consumption and biomarkers of exposure for HDL (R-squared = 0.39). CONCLUSIONS Levels of WBC, EPI8, DEH11 and HDL were statistically associated with biomarkers of exposure to cigarette smoking and demographics and life style factors. All of the predictors together explain 29%-41% of the variability in the BOPH.
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Affiliation(s)
- John H Warner
- Pharsight Corporation, a Certara Company, Mountain View, CA 94041-1530, USA
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17
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Alessandrini F, Beck-Speier I, Krappmann D, Weichenmeier I, Takenaka S, Karg E, Kloo B, Schulz H, Jakob T, Mempel M, Behrendt H. Role of oxidative stress in ultrafine particle-induced exacerbation of allergic lung inflammation. Am J Respir Crit Care Med 2009; 179:984-91. [PMID: 19264975 DOI: 10.1164/rccm.200807-1061oc] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
RATIONALE The effects of ultrafine particle inhalation on allergic airway inflammation are of growing interest. The mechanisms underlying these effects are currently under investigation. OBJECTIVES To investigate the role of oxidative stress on the adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFPs) on allergic airway inflammation. METHODS Ovalbumin-sensitized mice were exposed to EC-UFPs (504 microg/m(3) for 24 h) or filtered air immediately before allergen challenge and systemically treated with N-acetylcysteine or vehicle before and during EC-UFP inhalation. Allergic inflammation was measured up to 1 week after allergen challenge by means of bronchoalveolar lavage, cytokine/total protein assays, lung function, and histology. Isoprostane levels in lung tissue served to measure oxidative stress. Transmission electron microscopy served to localize EC-UFPs in lung tissue and both electrophoretic mobility shift assay and immunohistochemistry to quantify/localize nuclear factor-kappaB (NF-kappaB) activation. MEASUREMENTS AND MAIN RESULTS In sensitized and challenged mice EC-UFP inhalation increased allergen-induced lung lipid peroxidation and NF-kappaB activation in addition to inflammatory infiltrate, cytokine release, and airway hyperresponsiveness. Prominent NF-kappaB activation was observed in the same cell types in which EC-UFPs were detected. N-acetylcysteine treatment significantly reduced the adjuvant activity of EC-UFPs. In nonsensitized or sensitized but not challenged mice EC-UFP exposure induced a moderate increase in isoprostanes but no significant effect on other parameters of lung inflammation. CONCLUSIONS Our findings demonstrate a critical role for oxidative stress in EC-UFP-induced augmentation of allergen-induced lung inflammation, where EC-UFP exposure has potentiating effects in lung allergic inflammation. Our data support the concept that allergic individuals are more susceptible to the adverse health effects of EC-UFPs.
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Affiliation(s)
- Francesca Alessandrini
- Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, ZAUM Center for Allergy and Environment, Helmholtz Zentrum München, Neuherberg, Germany.
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18
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Mannarino E, Pirro M, Cortese C, Lupattelli G, Siepi D, Mezzetti A, Bertolini S, Parillo M, Fellin R, Pujia A, Averna M, Nicolle C, Notarbartolo A. Effects of a phytosterol-enriched dairy product on lipids, sterols and 8-isoprostane in hypercholesterolemic patients: a multicenter Italian study. Nutr Metab Cardiovasc Dis 2009; 19:84-90. [PMID: 18762410 DOI: 10.1016/j.numecd.2008.03.012] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2008] [Revised: 03/21/2008] [Accepted: 03/31/2008] [Indexed: 11/22/2022]
Abstract
BACKGROUND AND AIMS Plant sterols, added to several food sources, lower serum cholesterol concentrations. Plant sterol-induced cholesterol lowering is paralleled by a mild decrease in plasma levels of the antioxidant beta-carotene, the amount of this decrease being considered clinically non-significant. Whether the effect on lipid profile of daily consumption of plant sterol-enriched low-fat fermented milk (FM) is paralleled by a concomitant variation in a reliable marker of the oxidative burden like plasma isoprostane levels is unresolved. METHODS AND RESULTS The effect of plant sterol consumption on plasma lipid and isoprostane levels of hypercholesterolemic patients was evaluated in a multicenter, randomized double blind study. Hypercholesterolemic patients consumed a FM daily for 6 weeks. Subjects were randomized to receive either 1.6g of plant sterol-enriched FM (n=60) or control FM product (n=56). After 6 weeks of plant sterol-enriched FM consumption, LDL cholesterol was reduced from 166.2+/-2.0 to 147.4+/-2.8 mg/dL (p=0.01). A significant reduction was observed for total cholesterol (from 263.5+/-2.6 to 231.0+/-3.2mg/dL, p=0.01). There was greater LDL cholesterol lowering among hypercholesterolemic patients with higher LDL cholesterol at baseline. We found a reduction of plasma 8-isoprostane in patients taking plant sterol-enriched FM (from 43.07+/-1.78 to 38.04+/-1.14 pg/ml, p=0.018) but not in patients taking the control product (from 42.56+/-2.12 to 43.19+/-2.0 pg/ml, p=NS). Campesterol and beta-sitosterol levels were not influenced by phytosterol consumption. CONCLUSIONS Daily consumption of low-fat plant sterol dairy product favourably changes lipid profile by reducing LDL-cholesterol, and may also have an anti-oxidative effect through a reduction of plasma isoprostanes.
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Affiliation(s)
- E Mannarino
- Medicina Interna, Angiologia e Malattie da Arteriosclerosi, Università di Perugia, Perugia, Italy.
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19
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Increased plasma levels of 8-iso-PGF2alpha and IL-6 in an elderly population with depression. Psychiatry Res 2008; 161:59-66. [PMID: 18783834 DOI: 10.1016/j.psychres.2007.07.019] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2006] [Revised: 04/29/2007] [Accepted: 07/20/2007] [Indexed: 11/21/2022]
Abstract
Oxidative damage and immune-inflammatory activation have been suggested to play a role in depression. The purpose of the study was to investigate possible associations and interactions of these pathophysiological mechanisms in geriatric depression by determining the levels of plasma 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) and interleukin-6 (IL-6) in elderly depressed individuals. Subjects over 60 years of age with depression and controls were randomly selected from a population in the community after screening with the Geriatric Depression Scale. Plasma concentrations of 8-iso-PGF2alpha and IL-6 were measured in both groups. Depressed patients had significantly higher mean (+/-S.D.) 8-iso-PGF2alpha levels compared to healthy controls (245.01+/-179.92 pg/ml vs 97.64+/-42.72 pg/ml, respectively). Similarly, the same groups demonstrated significantly elevated IL-6 levels compared with controls (58.73+/-39.90 pg/ml vs 15.41+/-9.27 pg/ml). This study indicates an association between increased levels of plasma 8-iso-PGF2alpha and IL-6 with depressive symptomatology in elderly individuals and indicates the necessity for further investigation, possibly within the framework of an integrated involvement of oxidative damage and inflammation in the pathophysiology of depression in the elderly.
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20
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Roethig HJ, Feng S, Liang Q, Liu J, Rees WA, Zedler BK. A 12-month, randomized, controlled study to evaluate exposure and cardiovascular risk factors in adult smokers switching from conventional cigarettes to a second-generation electrically heated cigarette smoking system. J Clin Pharmacol 2008; 48:580-91. [PMID: 18319361 DOI: 10.1177/0091270008315316] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This randomized, controlled, forced-switching, open-label, parallel-group study in 97 adult male and female smokers of conventional cigarettes evaluated biomarkers of tobacco smoke exposure and cardiovascular risk factors. After baseline measurements, smokers were either switched to a second-generation electrically heated cigarette smoking system (EHCSS) or continued smoking conventional cigarettes for 12 months. Biomarkers of exposure and cardiovascular risk factors were measured at 0.5, 1, 2, 3, 4, 5, 6, 9, and 12 months. There was a rapid and sustained reduction in all biomarkers of exposure after switching to the EHCSS, with statistically significant reductions from baseline in nicotine equivalents (-18%), plasma cotinine (-16%), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (-73%), total 1-hydroxypyrene (-53%), urine mutagenicity (-52%), 4-aminobiphenyl hemoglobin adducts (-43%), carboxyhemoglobin AUC7-23 h (-80%), and 3-hydroxypropylmercapturic acid (-35%). These reductions in exposure in the EHCSS group were associated with statistically significant and pathophysiologically favorable changes in several cardiovascular risk factors, including white blood cell count (-0.78 x 10(3)/microL), hemoglobin (-0.16 g/dL), hematocrit (-0.44%), urine 11-dehydrothromboxane B2 (-374 ng/24 h), and high-density lipoprotein cholesterol (+5 mg/dL).
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Affiliation(s)
- Hans J Roethig
- Philip Morris USA Inc, Research Center, 4201 Commerce Road, Richmond, VA 23234, USA.
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21
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Yan W, Byrd GD, Ogden MW. Quantitation of isoprostane isomers in human urine from smokers and nonsmokers by LC-MS/MS. J Lipid Res 2007; 48:1607-17. [PMID: 17456897 DOI: 10.1194/jlr.m700097-jlr200] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
A simple, rapid liquid chromatography-tandem mass spectrometry method was developed to identify and quantitate in human urine the isoprostanes iPF(2 alpha)-III, 15-epi-iPF(2 alpha)-III, iPF(2 alpha)-VI, and 8,12-iso-iPF(2 alpha)-VI along with the prostaglandin PGF(2 alpha) and 2,3-dinor-iPF(2 alpha)-III, a metabolite of iPF(2 alpha)-III. Assay specificity, linearity, precision, and accuracy met the required criteria for most analytes. The urine sample storage stability and standard solution stability were also tested. The methodology was applied to analyze 24 h urine samples collected from smokers and nonsmokers on controlled diets. The results for iPF(2 alpha)-III obtained by our method were significantly correlated with results by an ELISA, although an approximately 2-fold high bias was observed for the ELISA data. For iPF(2 alpha)-III and its metabolite 2,3-dinor-iPF(2 alpha)-III, smokers had significantly higher concentrations than nonsmokers (513 +/- 275 vs. 294 +/- 104 pg/mg creatinine; 3,030 +/- 1,546 vs. 2,046 +/- 836 pg/mg creatinine, respectively). The concentration of iPF(2 alpha)-VI tended to be higher in smokers than in nonsmokers; however, the increase was not statistically significant in this sample set. Concentrations of the other three isoprostane isomers showed no trends toward differences between smokers and nonsmokers. Among smokers, the daily output of two type VI isoprostanes showed a weak correlation with the amount of tobacco smoke exposure, as determined by urinary excretion of total nicotine equivalents.
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Affiliation(s)
- Weiying Yan
- Department of Physiology and Pharmacology, Wake Forest University Medical Center, Winston-Salem, NC, USA
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22
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Mure K, Takeshita T, Morioka I, Arita M. [Effects of kakisu (persimmon vinegar) on plasma antioxidant power and urinary 8-isoprostane level]. Nihon Eiseigaku Zasshi 2007; 62:32-8. [PMID: 17334090 DOI: 10.1265/jjh.62.32] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVES To clarify the antioxidative effects of kakisu (persimmon vinegar), plasma antioxidant power and urinary oxidative stress level in healthy subjects were measured using enzyme immunological assays. METHODS Eighty-one subjects (age 30-69, 58.4 +/- 0.8) were randomly divided into two groups using a crossover design. Group A drank kakisu for 56 days starting in March, whereas group B drank kakisu for 54 days starting in June. Copper reducing equivalent level in plasma was measured as antioxidant power, and urinary 8-isoprostane (8-iso-prostaglandin F2alpha) level was measured as oxidative stress marker. RESULTS Baseline plasma antioxidant power and urinary 8-isoprostane level showed no significant correlation among the subjects in this study. By drinking kakisu for 8 weeks, total antioxidant power significantly increased, and urinary 8-isoprostane level decreased. Total antioxidant power increased more markedly in group A than in group B. In contrast, urinary oxidative stress level decreased more markedly in group B than in group A. Smoking habits significantly correlated with urinary 8-isoprostane level. Males were more sensitive to the antioxidative effects of kakisu than females. CONCLUSIONS Kakisu has antioxidative effects that increase plasma antioxidant power and reduce urinary 8-isoprostane level. Further study is needed to clarify the influence of season and gender on such antioxidative effects.
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Affiliation(s)
- Kanae Mure
- Department of Public Health, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama City, Wakayama 641-8509, Japan.
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Rossner P, Gammon MD, Terry MB, Agrawal M, Zhang FF, Teitelbaum SL, Eng SM, Gaudet MM, Neugut AI, Santella RM. Relationship between urinary 15-F2t-isoprostane and 8-oxodeoxyguanosine levels and breast cancer risk. Cancer Epidemiol Biomarkers Prev 2006; 15:639-44. [PMID: 16614103 DOI: 10.1158/1055-9965.epi-05-0554] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
To evaluate the role of oxidative stress in breast cancer, we measured urinary levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) and 8-oxodeoxyguanosine (8-oxodG) in 400 cases and 401 controls, participants of the Long Island Breast Cancer Study Project. We also analyzed the effect of different factors that are associated with oxidative stress and might influence 15-F(2t)-IsoP and 8-oxodG levels. We observed a statistically significant trend in breast cancer risk with increasing quartiles of 15-F(2t)-IsoP levels [odds ratio (OR), 1.25; 95% confidence interval (95% CI), 0.81-1.94; OR, 1.53; 95% CI, 0.99-2.35; OR, 1.88; 95% CI, 1.23-2.88, for the 2nd, 3rd, and 4th quartile relative to the lowest quartile, respectively; P(trend) = 0.002]. Although it is possible that increased levels may reflect the stress associated with recent treatment, the positive association was also observed when the analyses were restricted to case women for whom chemotherapy and radiation therapy had not yet been initiated at the time of the urine collection. The association with the highest quartile compared with lowest quartile of 15-F(2t)-IsoP was similar across strata of age, physical activity, fruit and vegetable intake, alcohol intake, cigarette smoking, body mass index, and menopausal status. We did not observe any association of breast cancer risk with 8-oxodG levels, but when cases with radiation treatment were removed from the analysis, a significant inverse trend (P = 0.04) was observed. Among controls, levels of 15-F(2t)-IsoP were higher among current cigarette smokers but did not differ by the amount of physical activity, fruit and vegetable intake, alcohol intake, body mass index, and menopausal status. Among controls, levels of 8-oxodG were higher among postmenopausal women and current and former cigarette smokers but did not differ by the other factors. In summary, our results suggest that urinary markers of lipid peroxidation and oxidative DNA damage may be associated with breast cancer risk.
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Affiliation(s)
- Pavel Rossner
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
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Abstract
F(2)-isoprostanes are a complex family of compounds produced from arachidonic acid via a free radical-catalyzed mechanism. Their quantification as a pathophysiological biomarker provides a unique opportunity to investigate lipid peroxidation in vascular diseases. Their measurement also provides an interesting biomarker for the rational dose selection of antioxidants in vascular diseases where oxidative stress might be involved. In addition to their use as biomarkers, some isoprostanes possess a biological activity. The 15-series F(2)- and E(2)-isoprostanes mediate vasoconstriction in different vascular beds and species. In addition, 15-F(2t)-IsoP induces smooth muscle cells mitogenesis and monocyte adhesion to endothelial cells. The data available supports but does not prove the hypothesis that isoprostanes are involved in vascular physiology and pathogenesis.
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Affiliation(s)
- Jean-Luc Cracowski
- Laboratoire de Pharmacologie, Inserm ESPRI, HP2 EA 3745, Faculté de Médecine de Grenoble, France.
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Kitano S, Hisatomi H, Hibi N, Kawano K, Harada S. Improved method of plasma 8-Isoprostane measurement and association analyses with habitual drinking and smoking. World J Gastroenterol 2006; 12:5846-52. [PMID: 17007051 PMCID: PMC4100666 DOI: 10.3748/wjg.v12.i36.5846] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method to examine the effects of drinking and smoking habits against the levels of plasma 8-isoprostane in healthy Japanese volunteers.
METHODS: Plasma 8-isoprostane was extracted with ODS gel suspension followed by NH2 Sep-Pak column. The 8-isoprostane fractions were assayed using a commercially available ELISA kit. We measured plasma 8-isoprostane levels in 157 healthy Japanese volunteers divided into three groups (64 non-habitual drinkers, 56 moderate drinkers and 37 habitual drinkers) according to their alcohol consumption per week. Genotypes of aldehyde dehydrogenase 2 (ALDH2) were also determined to investigate the plasma 8-isoprostane levels with reference to drinking habits. In addition, the plasma 8-isoprostane levels of 96 non-smokers and 61 smokers from the same subjects were compared.
RESULTS: Our method fulfilled all the requirements for use in routine clinical assays with respect to sensitivity, intra- and inter-assay reproducibility, accuracy and dynamic assay range. Significant increases of plasma 8-isoprostane levels were observed in female habitual drinkers when compared with those of non-habitual drinkers (t = 5.494, P < 0.0001) as well as moderate drinkers (t = 3.542, P < 0.005), and 8-isoprostane levels were also significantly different between ALDH2*2/1 and ALDH2*1/1 in the female habitual drinkers (t = 6.930, P < 0.0001), suggesting that excessive drinking of alcohol may increase oxidization stress, especially in females. On the contrary, no significant difference of the plasma 8-isoprostane levels was observed between non-smokers and smokers.
CONCLUSION: Our present method was proved to be a simple and accurate tool for measuring plasma 8-isoprostane. However, the clinical utility of plasma 8-isoprostane for drinking and smoking habits was limited since elevated 8-isoprostane levels were observed in female heavy drinkers, and no association was found between smokers and nonsmokers.
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Affiliation(s)
- Soichi Kitano
- Development Planning Section, Technology Development Department, SRL Inc., 5-6-50 Shinmachi, Hino-shi, Tokyo, 191-0002, Japan.
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Zedler BK, Kinser R, Oey J, Nelson B, Roethig HJ, Walk RA, Kuhl P, Rustemeier K, Schepers G, Von Holt K, Tricker AR. Biomarkers of exposure and potential harm in adult smokers of 3-7 mg tar yield (Federal Trade Commission) cigarettes and in adult non-smokers. Biomarkers 2006; 11:201-20. [PMID: 16760130 DOI: 10.1080/13547500600576260] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
The paper reports levels of 24-h urine nicotine and five of its major metabolites (expressed as nicotine-equivalents) and blood carboxyhaemoglobin as biomarkers of exposure to particulate- and gas-phase cigarette smoke, respectively, from an exploratory pilot study of adult smokers of 3.0-6.9 mg tar delivery (Federal Trade Commission (FTC) method) cigarettes. On multiple occasions over 6 weeks, blood high-sensitivity C-reactive protein (hs-CRP), fibrinogen, HDL- and LDL-cholesterol, and 24-h urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and 11-dehydro-thromboxane B2 (11-dehydro-TxB2) were also evaluated as biomarkers of potential harm. All the biomarkers examined, except for LDL-cholesterol, discriminated with high sensitivity and specificity between adult smokers and non-smokers overall. Except for HDL-cholesterol, all biomarker medians were greater in adult smokers than in non-smokers: urine nicotine-equivalents 64.514 versus < 0.034 nmol mg-1 creatinine (p<0.001), carboxyhaemoglobin 4.0 versus 0.4% saturation (p<0.001), hs-CRP 0.27 versus 0.12 mg dl-1 (p=0.05), fibrinogen 292 versus 248 mg dl-1 (p<0.001), HDL-cholesterol 46 versus 53 mg dl-1 (p=0.003), LDL-cholesterol 119 versus 109 mg dl-1 (p=0.18), urine 8-epi-PGF2alpha 1935 versus 1034 pg mg-1 creatinine (p<0.001) and urine 11-dehydro-TxB2 973 versus 710 pg mg-1 creatinine (p<0.001). All the biomarkers of exposure and most of the biomarkers of potential harm showed no time of sampling (by visit week) effect.
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Affiliation(s)
- B K Zedler
- Philip Morris USA, Richmond, VA 23261, USA.
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Wolfram R, Oguogho A, Palumbo B, Sinzinger H. Enhanced oxidative stress in coronary heart disease and chronic heart failure as indicated by an increased 8-epi-PGF(2alpha). Eur J Heart Fail 2005; 7:167-72. [PMID: 15701462 DOI: 10.1016/j.ejheart.2004.05.007] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2004] [Revised: 03/25/2004] [Accepted: 05/05/2004] [Indexed: 01/07/2023] Open
Abstract
The role of oxidation injury as an important factor in the pathophysiology of cardiomyopathy (CMP) has recently gained increasing interest. Semiquantitative analysis for isoprostane, 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)), and oxidised low-density lipoprotein (ox-LDL) of coronary vascular tissue samples derived from CMP patients revealed an increased extent and intensity of uptake as compared to the respective controls. To evaluate oxidative stress in vivo, we examined plasma, serum, salivary, and urinary 8-epi-PGF(2alpha) in patients with dilated CMP (n=20) and ischemic CMP (n=20) with decreased left ventricular ejection fraction (LVEF). Patients with coronary heart disease (CHD) (n=20) and 20 healthy, age-matched, and sex-matched controls were investigated in parallel. 8-Epi-PGF(2alpha) levels were correlated with the functional severity of heart failure [New York Heart Association (NYHA) classification] and LVEF. 8-Epi-PGF(2alpha) levels were matched according to risk factors (smoking and hypercholesterolemia) and were significantly higher in patients with CMP as compared to healthy controls and patients with CHD in all investigated compartments. A positive correlation between NYHA stages and 8-epi-PGF(2alpha), as well as a negative correlation to LVEF, could be demonstrated in a subgroup analysis. These findings reflect the enhanced oxidation injury in patients with CMP and, to a lesser extent, in CHD as compared to healthy controls, thus highly indicating the relevance of oxidative stress for the pathogenesis and progression of cardiovascular disease.
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Affiliation(s)
- Roswitha Wolfram
- Department of Angiology, Medical University of Vienna, Vienna, Austria
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Dietrich M, Hu Y, Block G, Olano E, Packer L, Morrow JD, Hudes M, Abdukeyum G, Rimbach G, Minihane AM. Associations between apolipoprotein E genotype and circulating F2-isoprostane levels in humans. Lipids 2005; 40:329-34. [PMID: 16028714 DOI: 10.1007/s11745-006-1390-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Apolipoprotein E (apoE), an important determinant of plasma lipoprotein metabolism, has three common alleles (epsilon2, epsilon3, and epsilon4). Population studies have shown that the risk of diseases characterized by oxidative damage, such as coronary heart disease and Alzheimer's disease, is significantly higher in epsilon4 carriers. We evaluated the association between apoE genotypes and plasma F2-isoprostane levels, an index of lipid peroxidation, in humans. Two hundred seventy-four healthy subjects (104 males, 170 females; 46.9 +/- 13.0 yr; 200 whites, 74 blacks; 81 nonsmokers, 64 passive smokers, and 129 active smokers) recruited for a randomized clinical antioxidant intervention trial were included in this analysis. ApoE genotype was determined by PCR and restriction enzyme digestion. Free plasma F2-isoprostane was measured by GC-MS. Genotype groups were compared using multiple regression analysis with adjustment for sex, age, race, smoking status, body mass index, plasma ascorbic acid, and beta-carotene. Subjects with epsilon3/epsilon4 and epsilon4/epsilon4 genotype (epsilon4-carriers) and with epsilon2/epsilon3 and epsilon3/epsilon3 (non-epsilon4-carriers) were pooled for analysis. In subjects with high cholesterol levels (total cholesterol above 200 mg/dl), plasma F2-isoprostane levels were 29% higher in epsilon4 carriers than in non-epsilon4-carriers (P= 0.0056). High-cholesterol subjects that are epsilon4 carriers have significantly higher levels of lipid peroxidation as assessed by circulating F2-isoprostane levels.
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Affiliation(s)
- Marion Dietrich
- School of Public Health, University of California, Berkeley, California, USA
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29
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Morrow JD. Quantification of Isoprostanes as Indices of Oxidant Stress and the Risk of Atherosclerosis in Humans. Arterioscler Thromb Vasc Biol 2005; 25:279-86. [PMID: 15591226 DOI: 10.1161/01.atv.0000152605.64964.c0] [Citation(s) in RCA: 344] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Enhanced oxidant stress occurring either locally in the vessel wall or systemically is implicated in the pathogenesis of atherosclerosis in humans. Nonetheless, evidence that oxidant stress is increased in vivo in association with this disease and that it can be quantified in living human beings has been lacking because of the unavailability of biomarkers to assess oxidant stress in humans. Recently, the development of methods to quantify the F
2
-isoprostanes (IsoPs), prostaglandin (PG)-like compounds derived from the free radical-catalyzed peroxidation of arachidonic acid, has allowed, for the first time to the author’s knowledge, a facile and accurate assessment of oxidant stress in vivo. The purpose of this brief review is to discuss the usefulness of quantifying IsoPs as an index of oxidative injury in association with atherosclerosis. F
2
-IsoPs can be measured in human biological fluids, such as plasma and urine, using highly precise assays. They have been shown to be increased in association in with a number of atherosclerotic risk factors, including cigarette smoking, hypercholesterolemia, diabetes mellitus, and obesity, among others. In addition, recent evidence suggests their quantification may represent an independent marker of atherosclerotic risk. A reduction in cardiovascular risk factors is associated with a decrease in IsoP formation in humans. Despite the fact that the role of oxidant stress in the pathogenesis of atherosclerosis is a hotly debated issue, current evidence suggests that the IsoPs represent a biomarker that has the potential to be of great importance in the assessment of human atherosclerotic cardiovascular disease.
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Affiliation(s)
- Jason D Morrow
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
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30
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Abstract
Isoprostanes, are a novel group of prostaglandin-like compounds that are biosynthesised from esterified polyunsaturated fatty acid (PUFA) through a non-enzymatic free radical-catalysed reaction. Several of these compounds possess potent biological activity, as evidenced mainly through their pulmonary and renal vasoconstrictive effects, and have short half-lives. It has been shown that isoprostanes act as full or partial agonists through thromboxane receptors. Both human and experimental studies have indicated associations of isoprostanes and severe inflammatory conditions, ischemia-reperfusion, diabetes and atherosclerosis. Reports have shown that F2-isoprostanes are authentic biomarkers of lipid peroxidation and can be used as potential in vivo indicators of oxidant stress in various clinical conditions, as well as in evaluations of antioxidants or drugs for their free radical-scavenging properties. Higher levels of F2-isoprostanes have been found in the normal human pregnancy compared to non-pregnancy, but their physiological role has not been well studied so far. Since bioactive F2-isoprostanes are continuously formed in various tissues and large amounts of these potent compounds are found unmetabolised in their free acid form in the urine in normal basal conditions with a wide inter-individual variation, their role in the regulation of normal physiological functions could be of further biological interest, but has yet to be disclosed. Their potent biological activity has attracted great attention among scientists, since these compounds are found in humans and animals in both physiological and pathological conditions and can be used as reliable biomarkers of lipid peroxidation.
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Affiliation(s)
- Samar Basu
- Section of Geriatrics and Clinical Nutrition Research, Faculty of Medicine, Uppsala University, Box 609, SE-751 25 Uppsala, Sweden.
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Schwedhelm E, Böger RH. Application of gas chromatography-mass spectrometry for analysis of isoprostanes: their role in cardiovascular disease. Clin Chem Lab Med 2004; 41:1552-61. [PMID: 14708879 DOI: 10.1515/cclm.2003.238] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Cardiovascular disease (CVD) is the major cause of death in the Western hemisphere. Oxidative stress is involved in the pathophysiology of cancer, neurodegenerative conditions and CVD. Lipid peroxidation is one of the oxidative modifications possible in biological systems. The isoprostanes are derivatives of one specific lipid, i.e., arachidonic acid, after lipid peroxidation. Several isoprostanes have been identified in biological tissues and fluids, among them 8-iso prostaglandin F2alpha (8-iso-PGF2alpha, 8-epi-PGF2alpha, iPF2alpha-III, 15-F2t-IsoP) and its metabolite, 2,3-dinor-4,5-dihydro-8-iso-PGF2alpha. The isoprostanes are reliable in vivo markers of lipid peroxidation in humans: they are endogenously formed, characteristic in structure, ubiquitous in nature, stable in- and ex vivo and reliably quantitatable. In this Review, different analytical approaches will be discussed including immunologic, chromatographic and spectrometric techniques with the main emphasis on mass spectrometry. Analysis of isoprostanes applying radio immunoassay (RIA), enzyme immunoassay (EIA), high performance-liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-tandem MS), gas chromatography-mass spectrometry (GC-MS) and GC-tandem MS will be exemplified in the field of cardiovascular research. Results from several clinical studies are included indicating the validity of isoprostanes as surrogate parameters of oxidative stress in cardiovascular disease.
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Affiliation(s)
- Edzard Schwedhelm
- Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Germany.
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Praticò D, Rokach J, Lawson J, FitzGerald GA. F2-isoprostanes as indices of lipid peroxidation in inflammatory diseases. Chem Phys Lipids 2004; 128:165-71. [PMID: 15037161 DOI: 10.1016/j.chemphyslip.2003.09.012] [Citation(s) in RCA: 86] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Isoprostanes are a new class of lipids, isomers of conventional enzymatically derived prostaglandins, which are produced in vivo primarily by a free radical-catalyzed peroxidation of polyunsaturated fatty acids. F2-isoprostanes, isomers of the enzyme-derived prostaglandin F2alpha, are the most studied species. Because of their mechanisms of formation, specific structural features that distinguish them from other free radical-generated products and chemical stability, they provide a reliable index of the oxidative component of several diseases in vivo. Consistent data suggest that formation of F2-isoprostanes is indeed altered in a variety of clinical settings associated with inflammation and oxidant stress. Moreover, measurement of F2-isoprostanes might provide a sensitive biochemical basis of dose-selection in studies of natural and synthetic antioxidants.
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Affiliation(s)
- Domenico Praticò
- Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
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Abstract
Among the isoprostanes, the 15-series F2-isoprostanes and 15-E2t-IsoP mediate vasoconstriction in different vascular beds and species. In addition, 15-F2t-IsoP induces smooth muscle cells mitogenesis and monocyte adhesion to endothelial cells. In clinical studies, 15-F2t-IsoP levels are increased in some vascular disorders involving atherosclerosis, ischemia-reperfusion and inflammation. Whether the same effects observed in vitro are observed consistently in vivo at physiological concentrations and whether these effects contribute to pathological states in vivo is still debated.
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Affiliation(s)
- Jean-Luc Cracowski
- Laboratoire de Pharmacologie, Faculté de Médecine de Grenoble, Domaine de la Merci, La Tronche 38700, France.
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Wolfram RM, Palumbo B, Chehne F, Palumbo R, Budinsky AC, Sinzinger H. (ISO) Prostaglandins in saliva indicate oxidation injury after radioiodine therapy. ACTA ACUST UNITED AC 2004; 23:183-8. [PMID: 15153361 DOI: 10.1016/s0212-6982(04)72279-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
UNLABELLED As salivary glands concentrate radioiodine the radiation injury associated with 131I-therapy may result in sialoadenitis and xerostoma leading to a lasting impaired quality of life. Recently we reported about prostaglandin concentration changes as biochemical markers for radiation injury. Isoprostanes, a new family of prostaglandin-like compounds, have been demonstrated to be reliable markers for oxidation injury in vivo. PATIENTS AND METHODS In this study we examined the levels of 8-epi-PGF2alpha, the major member of the isoprostane family in 24 patients undergoing 1311 treatment in different doses for hyperthyroidism and differentiated thyroid cancer. 6 healthy sex and age-matched volunteers were monitored in parallel. Saliva(iso)prostaglandins were determined before 131I treatment, as well as 1, 3, 7, 14, 21, and 28 days, and 2, 3, and 6 months after therapy. RESULTS 8-epi-PGF2alpha showed a significant 1311 dose-dependent temporary increase. The alterations were comparable in all investigated patients and significantly higher in cigarette smokers. TXB2 and 6-oxo-PGF, showed a dose-dependent increase too. TXB2 was higher in cigarette smokers and 6-oxo-PGF1alpha lower as compared to non-smokers. CONCLUSION These results clearly demonstrate a dose- and time-dependent tissue (TXB2, 6-oxo-PGF1alpha) and oxidation in-jury (8-epi-PGF2alpha) after 131I-therapy in the salivary glands.
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Affiliation(s)
- R M Wolfram
- Departments of Angiology, University of Vienna, Austria
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Abstract
The relative importance of mechanisms relevant to smoking-induced vascular injury is poorly understood. Cigarette smoke is a source of free radicals but also results in cellular activation and consequent generation of free radicals in vivo. Here we consider several approaches to estimating the consequences of free radical generation in vivo, using measurements of modified lipids, proteins, and DNA. Smoking appears to result in elevation of several biomarkers of oxidant stress, some in a dose-related fashion. There is also some evidence that disordered endothelial function in smokers may be partly attributable to oxidant stress. Other effects of smoking on hemostatic activation, sympathoadrenal function, and lipoprotein structure and function may also be modulated by smoking-induced oxidant stress. The emergence and application of rational quantitatively reliable indexes of oxidant stress in vivo is likely to elucidate the relative contribution of oxidant stress to smoking-induced vascular injury.
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Affiliation(s)
- Anne Burke
- Gastrointestinal Division and the Center for Experimental Therapeutics, Hospital of the University of Pennsylvania, Philadelphia, PA 19104-6084, USA
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36
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Keaney JF, Larson MG, Vasan RS, Wilson PWF, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 2003; 23:434-9. [PMID: 12615693 DOI: 10.1161/01.atv.0000058402.34138.11] [Citation(s) in RCA: 1024] [Impact Index Per Article: 46.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To determine the clinical conditions associated with systemic oxidative stress in a community-based cohort. Information regarding cardiovascular risk factors associated with systemic oxidative stress has largely been derived from highly selected samples with advanced stages of vascular disease. Thus, it has been difficult to evaluate the relative contribution of each cardiovascular risk factor to systemic oxidative stress and to determine whether such risk factors act independently and are applicable to the general population. METHODS AND RESULTS We examined 2828 subjects from the Framingham Heart Study and measured urinary creatinine-indexed levels of 8-epi-PGF2alpha as a marker of systemic oxidative stress. Age- and sex-adjusted multivariable regression models were used to assess clinical correlates of oxidative stress. In age- and sex-adjusted models, increased urinary creatinine-indexed 8-epi-PGF2alpha levels were positively associated with female sex, hypertension treatment, smoking, diabetes, blood glucose, body mass index, and a history of cardiovascular disease. In contrast, age and total cholesterol were negatively correlated with urinary creatinine-indexed 8-epi-PGF2alpha levels. After adjustment for several covariates, decreasing age and total/HDL cholesterol ratio, sex, smoking, body mass index, blood glucose, and cardiovascular disease remained associated with urinary 8-epi-PGF2alpha levels. CONCLUSIONS Smoking, diabetes, and body mass index were highly associated with systemic oxidative stress as determined by creatinine-indexed urinary 8-epi-PGF2alpha levels. The effect of body mass index was minimally affected by blood glucose, and diabetes and may suggest an important role of oxidative stress in the deleterious impact of obesity on cardiovascular disease.
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Affiliation(s)
- John F Keaney
- Evans Memorial Department of Medicine, Boston University School of Medicine, Whitaker Cardiovascular Institute, 715 Albany St, Rm W507, Boston, MA 02118, USA.
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Cracowski JL, Durand T, Bessard G. Isoprostanes as a biomarker of lipid peroxidation in humans: physiology, pharmacology and clinical implications. Trends Pharmacol Sci 2002; 23:360-6. [PMID: 12377577 DOI: 10.1016/s0165-6147(02)02053-9] [Citation(s) in RCA: 234] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Isoprostanes are a complex family of compounds produced from arachidonic acid via a free-radical-catalyzed mechanism. They can be quantified as reliable markers of lipid peroxidation. Among the isoprostanes, 15-F(2t)-IsoP and 15-E(2t)-IsoP are biologically active and mediate vasoconstriction and bronchoconstriction and augment nociception. These effects are thought to be mediated via the activation of prostanoid TP receptors, with isoprostanes acting as full or partial agonists. A strong link between lipid peroxidation and diseases associated with ischaemia-reperfusion, atherosclerosis and inflammation has been suggested by elevated levels of F(2)-isoprostanes observed in such diseases. Thus, quantification of F(2)-isoprostanes as a pathophysiological marker provides a unique opportunity to investigate lipid peroxidation in human diseases and provides an interesting biomarker for rational dose selection of antioxidants in diseases where oxidative stress might be involved.
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Abstract
Lipid lowering has been shown to be effective in preventing primary and recurrent cardiovascular events and to save life. Statins almost exclusively used for this purpose meanwhile became one of the most widely prescribed families of drugs world-wide. Myopathies--mainly not well characterized--are the major group of side effects. We here review different types of clinical appearances, localizations, symptoms and the biochemical background. The data indicate that severe muscular side effects are rare. Patients and their doctors, however, easily overlook mild ones. Myopathic symptoms without any known biochemical correlate are not rare. No general guideline exists about exact diagnosis and differential diagnosis. Strict adherence to the measures of life-style change and performance of regular exercise can even further enhance significantly these side effects. Much more research should be directed onto the pathophysiological (genetic?) background to finally evaluate possible therapeutic consequences rather than simply to withdraw or change the respective statin.
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Affiliation(s)
- Helmut Sinzinger
- Department of Nuclear Medicine, University of Vienna, A-1090 Vienna, Austria.
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