Modulation of oxidative stress: pharmaceutical and pharmacological aspects 2018

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Bleomycin-induced trans lipid formation in cell membranes and in liposome models

Cell cultures of NTera-2 cells incubated with bleomycin and liposomes as biomimetic models of cell membranes were used for examining some novel aspects of drug-metal induced reactivity with unsaturated lipids under oxidative conditions. In cell cultures, bleomycin was found for the first time to cause the formation of trans fatty acids. The chemical basis of this transformation was ascertained by liposome experiments, using bleomycin-iron complexes in the presence of thiol as a reducing agent that by incubation at 37 °C gave rise to the thiyl radical-catalysed double bond isomerisation of membrane phospholipids. The effect of oxygen and reagent concentrations on the reaction outcome was studied. An interesting scenario of free radical reactivity is proposed, which can be relevant for understanding the role of membrane lipids in antitumoral treatments and drug carrier interaction.Fil: Cort, Aysegul. Akdeniz University. Faculty of Medicine; Turquía. Consiglio Nazionale delle Ricerche; ItaliaFil: Ozben, Tomris. Akdeniz University. Faculty of Medicine; TurquíaFil: Sansone, Anna. Consiglio Nazionale delle Ricerche; ItaliaFil: Barata Vallejo, Sebastian. Consiglio Nazionale delle Ricerche; Italia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chatgilialoglu, Chryssostomos. Demokritos National Centre For Scientific Research; GreciaFil: Ferreri, Carla. Consiglio Nazionale delle Ricerche; Itali

Multidrug Resistance-Associated Protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine Sulfoximine

BACKGROUND: Multidrug resistance mediated by the multidrug resistance-associated protein 1 (MRP1) decreases cellular drug accumulation. The exact mechanism of MRP1 involved multidrug resistance has not been clarified yet, though glutathione (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine (NAC) is a pro-glutathione drug. DL-Buthionine (S,R)-sulfoximine (BSO) is an inhibitor of GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1-mediated vincristine resistance in Human Embryonic Kidney (HEK293) and its MRP1 transfected 293MRP cells. Human Embryonic Kidney (HEK293) cells were transfected with a plasmid encoding whole MRP1 gene. Both cells were incubated with vincristine in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. GSH, Glutathione S-Transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs. RESULTS: N-acetylcysteine increased the resistance of both cells against vincristine and BSO decreased NAC-enhanced MRP1-mediated vincristine resistance, indicating that induction of MRP1-mediated vincristine resistance depends on GSH. Vincristine decreased cellular GSH concentration and increased GPx activity. Glutathione S-Transferase activity was decreased by NAC. CONCLUSION: Our results demonstrate that NAC and BSO have opposite effects in MRP1 mediated vincristine resistance and BSO seems a promising chemotherapy improving agent in MRP1 overexpressing tumor cells

Acute effects of hemodialysis on oxidative stress parameters in chronic uremic patients: Comparison of two dialysis membranes

Uremic state and hemobioincompatibility are implicated in subclinical inflammation and oxidative stress and progression of atherosclerosis in the hemodialysis (HD) population. To what extent different dialysis membranes contribute to oxidative stress induced by a dialysis procedure per se is still a subject of debate. Fifteen HD patients and 15 healthy controls were enrolled in this study. Patients received two index HD sessions with a cuprophane and polysulfone membrane two weeks apart. Blood samples were collected at baseline and then before and after HD sessions. We determined serum thiobarbituric acid, protein carbonyl, and serum nitrite/nitrate levels as markers of oxidative damage. We also measured erythrocyte glutathione level, catalase, superoxide dismutase and glutathione peroxidase activity, and serum vitamin C and E levels as antioxidant markers. At baseline, HD patients, in comparison with normal controls, had a trend towards increased oxidant state and depletion of antioxidants. Cuprophane dialysis induced a higher increase in production of oxidants, along with a lower compensatory increase of antioxidants when compared with polysulfone dialysis. In conclusion, a single HD session, even when conducted with a biocompatible membrane, appears to play an important role in the imbalance between ROS production and antioxidant defense, but to a milder extent than cuprophane dialysis

Diagnostic proteomic biomarkers to detect kidney diseases

Urinary proteomics is primarily applied to the study of renal and urogenital tract disorders. Here are reported two distinct successful examples of this approach for the discovery of early urinary biomarkers of kidney­ related dysfunctions: diabetic nephropathy (DN), a well ­known complication of diabetes frequently leading to dialysis, and drug­induced nephrotoxicity, a possible condition caused by medication ­overuse headache (MOH). Early detection of kidney disorders based on selective biomarkers could permit to diagnose patients at the initial stage of the disease, where the therapy is still possible to stop or prevent occurrence of advance disease. Urine samples were first concentrated and desalted. Subsequently, they were subjected to two­-dimensional gel electrophoresis (2­DE) coupled to mass spectrometry (MS) for protein identification. Furthermore, some proteins were verified by Western blot and ELISA test. In diabetes-­related study, 11 differentially expressed proteins were detected (8 up­regulated and 3 down­regulated) in type 2 diabetic (T2D) and T2DN patients compared to the healthy control subjects. In MOH study, a total of 21 over­excreted proteins was revealed in urine of non­-steroidal anti­inflammatory drugs (NSAIDs) and mixtures abusers vs controls. Particularly, 4 proteins were positively validated by immunoblotting and ELISA. Urinary proteomics allows non­invasive assessment of renal diseases at an early stage by the identification of characteristic protein pattern

dynamic thiol disulphide homeostasis before and after radical prostatectomy in patients with prostate cancer

AbstractThiol groups are important anti-oxidants and essential molecules protecting organism against the harmful effects of reactive oxygen species (ROS). The aim of our study is to evaluate thiol–disulphide homeostasis with a novel recent automated method in patients with localized prostate cancer (PC) before and six months after radical prostatectomy (RP). 18 patients with PC and 17 healthy control subjects were enrolled into the study. Blood samples were collected from the controls subjects and patients before and six months after RP. Thiol–disulphide homeostasis was determined using a recently developed novel method. Prostate-specific antigen (PSA), albumin, total protein, total thiol, native thiol, disulphide and total antioxidant status (TAS) were measured and compared between the groups. Native thiol, total thiol and TAS levels were significantly higher in the control group than the patients before RP (p < .001). There was a non-significant increase in the native thiol, total thiol and TAS levels i..

Results of the first survey of the EFLM Task Force Preparation of Labs for Emergencies (TF-PLE)

This survey includes a series of questions about the nature, organization, and preparedness for emergencies, was created using Google forms, officially mailed to over 12,000 potential EFLM contacts with an official newsletter to collect responses between May 8 and June 8, 2023. Although obviously not representative of all European countries, the collected data provides an overview of the current situation with respect to laboratory readiness for emergencies

Disruption of laboratory activities during the COVID-19 pandemic: results of an EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) survey

Background: The EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) created a survey that has been distributed to its members for gathering information on the key hazards experienced by European medical laboratories during the COVID-19 pandemic. Methods: The survey was distributed to over 12,000 potential contacts (laboratory workers) via an EFLM newsletter, with responses collected between May 8 and June 8, 2023. Results: Two hundred replies were collected and examined from European laboratories. 69.7% and 78.1% of all responders said they were short on non-COVID and COVID reagents, respectively. Exactly half of respondents (50.0%) said that they could not complete all laboratory tests required for a specific period, but this figure climbed to 61.2% for COVID tests. Finally, 72.3% of respondents expressed exhaustion during the pandemic, and 61.2% reported increasing patient hostility. Conclusions: The COVID-19 pandemic had a significant impact on laboratory medicine in Europe. Cultural change, proactive planning, and even re-engineering in some parts of the laboratory industry may thus be necessary to prepare for future challenges

Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis

Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences