F2-isoprostanes can mediate bleomycin-induced lung fibrosis

F2-isoprostanes (F2-IsoPs) have been considered markers of oxidative stress in various pulmonary diseases, but little is known about their possible role in pulmonary fibrosis. In this study, we have investigated the potential key role of F2-IsoPs as markers and mediators of bleomycin (BLM)-induced pulmonary fibrosis in rats. During the in vivo study, plasma F2-IsoPs showed a peak at 7 days and remained elevated for the entire experimental period. Lung F2-IsoP content nearly tripled 7 days following the intratracheal instillation of BLM, and by 28 days, the value increased about fivefold compared to the controls. Collagen deposition correlated with F2-IsoP content in the lung. Furthermore, from day 21 onwards, lung sections from BLM-treated animals showed α-smooth muscle actin (α-SMA) positive cells, which were mostly evident at 28 days. In vitro studies performed in rat lung fibroblasts (RLF) demonstrated that either BLM or F2-IsoPs stimulated both cell proliferation and collagen synthesis. Moreover, RLF treated with F2-IsoPs showed a significant increase of α-SMA expression compared to control, indicating that F2-IsoPs can readily activate fibroblasts to myofibroblasts. Our data demonstrated that F2-IsoPs can be mediators of key events for the onset and development of lung fibrosis, such as cell proliferation, collagen synthesis and fibroblast activation. Immunocytochemistry analysis, inhibition and binding studies demonstrated the presence of the thromboxane A2 receptor (TP receptor) on lung fibroblasts and suggested that the observed effects may be elicited through the binding to this receptor. Our data added a new perspective on the role of F2-IsoPs in lung fibrosis by providing evidence of a profibrotic role for these mediators in the pathogenesis of pulmonary fibrosis

Increased F2-isoprostane levels in semen and immunolocalization of the 8-iso prostaglandin F2α in spermatozoa from infertile patients with varicocele

Polyunsaturated fatty acid damages lead to alterations in sperm function. This study aimed to investigate the involvement of F2-isoprostanes (F2-IsoPs), oxidized lipid products from arachidonic acid, in sperm quality impairment. For this purpose, F2-IsoP levels in semen and F2-IsoP localization in spermatozoa were explored in infertile subjects affected by idiopathic infertility or varicocele, as well as in fertile men. As compared to fertile men, in the idiopathic infertility and varicocele groups, sperm concentration, motility, morphology, viability, and fertility index were significantly lower and the mean scores concerning sperm apoptosis, necrosis, and immaturity were significantly higher. The idiopathic infertile group showed a reduction in sperm motility and fertility index, as well as an increase of apoptosis and necrosis percentages, in comparison to the varicocele group. The varicocele group showed the highest levels of F2-IsoPs, a significant increase of sperm immaturity, and a significant correlation between F2-IsoP levels and sperm immaturity. 8-Iso Prostaglandin F2α, biomarker of in vivo F2-IsoP, was clearly localized in sperm midpiece and cytoplasmic residues. Data show that F2-IsoP formation is relevant in semen and sperm from infertile patients with varicocele and high percentage of immaturity, suggesting that a correct fatty acid integrity is needed for sperm maturation

Pro-Atherogenic and Pro-Oxidant Diets Influence Semen and Blood Traits of Rabbit Bucks

: Many dietary factors can affect sperm traits. We compared the effect of diets rich in pro-oxidant (flaxseed oil) and pro-atherogenic (coconut oil) substances without added antioxidants on semen traits, using the rabbit as an animal model. Thirty rabbit bucks (8 months old) were fed three diets for 150 days: CNT (control) a standard diet; HA (high-atherogenic) standard diet + 3% coconut oil, and HO (high-oxidizing) standard diet + 3% flaxseed oil. Semen samples were collected weekly for the evaluation of qualitative traits (kinetics, viability) and the oxidative damage (MDA and cytokines). Blood was collected at the start (T0) and end (T8) of the experimental period for the assessment of the oxidative damage (MDA and isoprostanoids), lipid profile, and testosterone. A worsening of sperm kinetics and viability was recorded in the HA group. Lipid oxidation in seminal plasma, as well as isoprostanoids in blood (F3-IsoPs and F4-NeuroPs), increased in both the HO and HA groups. A high level of TNF-α, a marker of inflammatory status, was recorded in the seminal plasma of the HA group. The resulting outcomes were mainly attributable to the different fatty acid profiles (SFA vs. PUFA) of the diets, which modulated an inflammatory/oxidative response

measles mumps and rubella vaccination and autism misperception miscommunication vs scientific evidence results of a blinded anonymous italian survey

Herd immunity towards measles, one of the 20 most lethal diseases in human history, has been recently challenged on a global scale. Despite a missing causal relationship, vaccine fear has triggered a global anti vaccine movement. We investigated i) the extent of the vaccination-autism false belief in a selected Italian population from two geographical areas with and without an ongoing epidemics for a potentially vaccination-preventable infectious disease (Neisseria meningitidis, groups C and B); ii) the corresponding information source; and iii) the belief in a possible global conspiracy. Four different population sub-categories (I-general population; II-parents of autistic children; III-paramedics; IV-physicians, biologists and pharmacists; n=424) were administered anonymous questionnaires. A total of 30.1% of the general population and the 54.5% of autism parents participants believed in a vaccine-autism relationship (P<0.0001). The web was the major information source for the general population (35.3%). A total of 41.6% of the general population believes in a cover up of potential conflicts of interests by the Institutions. The belief in the autism-vaccination link was also positively related to the parenthood of an autistic child (OR:5.78, 95%CI: 2.36 to 14.12). We conclude that, against scientific evidence, information source and emotional involvement are major influencers of the misperception in the vaccine-autism paradigm, potentially fuelling the resurgence of vaccinepreventable diseases with major public health consequences

Review Article Isoprostanes and 4-Hydroxy-2-nonenal: Markers or Mediators of Disease? Focus on Rett Syndrome as a Model of Autism Spectrum Disorder

Lipid peroxidation, a process known to induce oxidative damage to key cellular components, has been implicated in several diseases. Following three decades of explorations mainly on in vitro models reproducible in the laboratories, lipid peroxidation has become increasingly relevant for the interpretation of a wide range of pathophysiological mechanisms in the clinical setting. This cumulative effort has led to the identification of several lipid peroxidation end-products meeting the needs of the in vivo evaluation. Among these different molecules, isoprostanes and 4-hydroxy-2-nonenal protein adducts appear to be particularly interesting. This review shows how specific oxidation products, deriving from polyunsaturated fatty acids precursors, are strictly related to the clinical manifestations and the natural history of Rett syndrome, a genetically determined neurodevelopmental pathology, currently classified among the autism spectrum disorders. In our experience, Rett syndrome offers a unique setting for physicians, biologists, and chemists to explore the borders of the lipid mediators concept

Isoprostanoids in clinical and experimental neurological disease models

Isoprostanoids are a large family of compounds derived from non-enzymatic oxidation of polyunsaturated fatty acids (PUFAs). Unlike other oxidative stress biomarkers, they provide unique information on the precursor of the targeted PUFA. Although they were discovered about a quarter of century ago, the knowledge on the role of key isoprostanoids in the pathogenesis of experimental and human disease models remains limited. This is mainly due to the limited availability of highly purified molecules to be used as a reference standard in the identification of biological samples. The accurate knowledge on their biological relevance is the critical step that could be translated from some mere technical/industrial advances into a reliable biological disease marker which is helpful in deciphering the oxidative stress puzzle related to neurological disorders. Recent research indicates the value of isoprostanoids in predicting the clinical presentation and evolution of the neurological diseases. This review focuses on the relevance of isoprostanoids as mediators and potential biomarkers in neurological diseases, a heterogeneous family ranging from rare brain diseases to major health conditions that could have worldwide socioeconomic impact in the health sector. The current challenge is to identify the preferential biochemical pathways that actually follow the oxidative reactions in the neurological diseases and the consequence of the specific isoprostanes in the underlying pathogenic mechanisms