The effect of omega- 3 polyunsaturated fatty acids on endothelial tight junction occludin expression in rat aorta during lipopolysaccharide-induced inflammation

Objective(s): Occludin is essential for proper assembly of tight junctions (TJs) which regulate paracellular endothelial permeability. Omega-3 polyunsaturated fatty acids (Ω-3 PUFA) protect endothelial barrier function against injury. Materials and Methods: We examined anti-inflammatory effect of Ω-3 PUFA intake (30 mg/kg/day for 10 days) on expression and location of occludin in the aorta of adult Wistar rats after a single dose of bacterial lipopolysaccharide (LPS, Escherichia coli, 1 mg/kg). The ultrastructure of TJs after LPS administration was also investigated. We measured plasma levels of C-reactive protein (CRP), Malondialdehyde (MDA) and CD68 expression and determined the total activity of NO synthase (NOS) in the aortic tissue. Results:LPS induced a significant decrease of occludin expression accompanied by structural alterations of TJs. Levels of CRP, MDA, CD68 and NOS activity were elevated after LPS injection compared to controls indicating presence of moderate inflammation. Ω-3 PUFA supplementation did not affect occludin expression in treated inflammatory group. However they reduced CRP and MDA concentration and CD68 expression, but conversely, they increased NOS activity compared to inflammatory group. Conclusion:Our results indicate that a single dose of LPS could have a long-term impact on occludin expression and thus contribute to endothelial barrier dysfunction. 10-day administration of Ω-3 PUFA had partial anti-inflammatory effects on health of rats without any effect on occludin expression

Differences in Distribution and Biological Effects of F3O4@PEG Nanoparticles in Normotensive and Hypertensive Rats—Focus on Vascular Function and Liver

We investigate the distribution and biological effects of polyethylene glycol (PEG)-coated magnetite (Fe3O4@PEG) nanoparticles (~30 nm core size, ~51 nm hydrodynamic size, 2 mg Fe/kg/day, intravenously, for two days) in the aorta and liver of Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). Fe3O4@PEG had no effect on open-field behaviour but reduced the blood pressure (BP) of Fe3O4@PEG-treated SHR (SHRu) significantly, compared to both Fe3O4@PEG-treated WKY (WKYu) and saline-treated control SHR (SHRc). The Fe3O4@PEG content was significantly elevated in the aorta and liver of SHRu vs. WKYu. Nitric oxide synthase (NOS) activity was unaltered in the aorta, but significantly increased in the liver of SHRu vs. SHRc. In the aorta, Fe3O4@PEG treatment increased eNOS, iNOS, NRF2, and DMT1 gene expression (considered main effects). In the liver, Fe3O4@PEG significantly elevated eNOS and iNOS gene expression in SHRu vs. SHRc, as well as DMT1 and FTH1 gene expression (considered main effects). Noradrenaline-induced contractions of the femoral arteries were elevated, while endothelium-dependent contractions were reduced in SHRu vs. SHRc. No differences were found in these parameters in WKY rats. In conclusion, the results indicated that the altered haemodynamics in SHR affect the tissue distribution and selected biological effects of Fe3O4@PEG in the vasculature and liver, suggesting that caution should be taken when using iron oxide nanoparticles in hypertensive subjects

Potencial markers and metabolic processes involved in mechanism of radiation-induced heart injury

Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra and intercellular signaling to alter cell and tissue function. In the case of chest irradiation it can affect the heart, blood vessels and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction and ultimate failing of the heart occur as a pathological entity - "radiation-induced heart disease" (RIHD) that is major source of morbidity and mortality. The purpose of the review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant, tendency of increased levels of 8-hydroxy-2’-deoxyguanosine and malondialdehyde in the HRW group. This mild increase may be indicative of the hormetic effects of molecular hydrogen that occurred prior to the significant clinical improvements reported in previous longer-term studies. The favorable trends in this study in conjunction with previous animal and clinical findings suggest that HRW may serve as an important adjuvant therapy for promoting and maintaining optimal health and wellness. Longer term studies focused on prevention, maintenance, or treatment of NAFLD and early stages of NASH are warranted