Ivermectin (IVM) is a drug from the group of anthelmintics used in veterinary and human medicine. Recently, interest in IVM has increased as it has been used for the treatment of some malignant ...diseases, as well as viral infections caused by the Zika virus, HIV-1 and SARS-CoV-2. The electrochemical behaviour of IVM was investigated using cyclic (CV), differential pulse (DPV) and square wave voltammetry (SWV) at glassy carbon electrode (GCE). IVM showed independent oxidation and reduction processes. The effect of pH and scan rate indicated the irreversibility of all processes and confirmed the diffusion character of oxidation and reduction as an adsorption-controlled process. Mechanisms for IVM oxidation at the tetrahydrofuran ring and reduction of the 1,4-diene structure in the IVM molecule are proposed. The redox behaviour of IVM in a biological matrix (human serum pool) showed a pronounced antioxidant potential similar to that of Trolox during short incubation, whereas a prolonged stay among biomolecules and in the presence of an exogenous pro-oxidant (tert-butyl hydroperoxide, TBH) resulted in a loss of its antioxidant effect. The antioxidant potential of IVM was confirmed by voltametric methodology which is proposed for the first time.
The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, ...which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (-IRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) in +IRF compared with -IRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels in +IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11b + dendritic cells and their positioning within lymph nodes in +IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats.
Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize ...new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (
-
) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as
-hydroxyurea derivatives (
,
and
), 3,5-di-tert-butylphenol derivatives (
,
,
,
and
), urea derivatives (
,
and
) and "type B hydroxamic acids" (
and
). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests. The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (
,
,
,
,
,
and
) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors
,
,
,
and
showed good antioxidant properties.
Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated ...by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).
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•Antidepressants alleviated pain hypersensitivity in rats with osteoarthritis (OA).•Duloxetine, unlike vortioxetine, depressed burrowing behavior in OA rats.•Vortioxetine improved cognitive performance in male and female OA rats.•Duloxetine improved cognitive performance only in female OA rats.•Duloxetine induced cardiac oxidative damage in female OA rats.
Disruption of the redox balance in the body causes oxidative stress that can initiate many diseases. While antioxidants reduce the level of oxidizing compounds in the medium, prooxidants promote the ...opposite process and have been used in therapies in particular those of cancer diseases. In this study, a series of azolyl lactones, were tested in human serum as a biological matrix and the obtained values of their oxy scores (OS) were compared. The antioxidative properties of these compounds were also tested under conditions of induced oxidative stress using an external prooxidant, t-butylhydroperoxide. The results showed that the sulphur analogue 4-azolyl coumarin 5 has the best antioxidant properties (OS ?2.2), while the halogenated derivatives of pyrazolylcoumarin 7 and 8 act as prooxidants, but successfully resist oxidative stress (OS 2.7 and 2.0, respectively). Related phthalides and isocoumarins showed prooxidative properties, but azolyl isocoumarins 10 and 11 show the strongest resistance to oxidative stress, reflected in their negative oxy score value (OS ?2.1 and ?1.1, respectively). The results demonstrated that combining two pharmacophores with known redox properties can produce potent compounds in both directions, with the antioxidative and the prooxidative characteristics.
An imbalance between oxidants and antioxidants in favour of oxidants, potentially leading to damage, is termed oxidative stress. Antioxidants (AO), either enzymatic or non-enzymatic, are the ones ...that can reduce diverse effects of pro-oxidants such as DNA, proteins and lipids damage. Chalcones (1,3-diaryl-2-propen-1-ones) are open chain flavonoids that are widely biosynthesized in plants. Aim of this study was to test antioxidative potency of 15 chalcones (Chs) in in vitro model in serum (native conditions), so as with exogenously induced oxidative stress.
Oxidative stress was induced in serum samples of healthy individuals with 0.25 mmol/L terc-buthyl-hydroperoxide (TBH), and then we monitored the effects of various concentrations of chalcones on oxidative stress parameters: total antioxidative status (TAS), total oxidative status (TOS), total concentration of sulfhydryl group (SHG) and prooxidative-antioxidative balance (PAB), and calculated prooxidative score, antioxidative score, and oxy score (OS). Nonparametric repeated measures ANOVA (Friedman's test) was used for comparison of antioxidative potency of samples with 15 different chalcones, in a native state and upon TBH influence. Spearman's nonparametric correlation analysis was used for estimation of relation between different parameters.
Negative Oxy Score (OS) values for Chs11-15 showed significantly stronger antioxidative potency compared to other investigated chalcones (p < 0.05). Ch11, Ch13 and Ch14 remained with negative OS even after TBH addition, whereas OS of Ch12 and Ch15 became positive, with small nominal values. Samples with Ch11 and Ch13 showed significant negative correlation between TAS and TOS (p < 0.05 for both), but in Ch14 sample the negative correlation existed between TAS and PAB (p < 0.05).
Lower value of OS (i.e. better antioxidative potency) was noticed in samples with Ch11-Ch15. Electron-donor effects of substituent groups as a structural part of these chalcones could explain its antioxidative capability. Phenolic and methyl groups are responsible for antioxidative ability enhancement of five chalcones with the best activity.
•In vitro biological model system.•The best antioxidative properties showed methyl-, phenol- and nitro- chalcones.•Further investigation should lead to chalcones use in human medicine.
There is a growing body of evidence that tomato consumption reduces the risk of cardiovascular disease, through antioxidative, anti-inflammatory and hypotensive effects. We compared the effects of ...polyphenol-enriched and standard tomato juice on parameters of lipid and oxidative status and blood pressure in subjects with stage 1 hypertension. The experimental group (
n
= 13) was supplemented with 200 g of tomato fruit juice enriched with 1 g of ethanolic extract of whole tomato fruit, while the control group (
n
= 13) was consuming 200 g tomato fruit juice. Before and after the treatment, blood samples were collected, and blood pressure was measured. Markers of oxidative stress and antioxidative defense: paraoxonase (PON1), thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), total oxidant status (TOS), pro-oxidant-antioxidant balance (PAB) and C reactive protein (CRP) were determined in serum. Prothrombin time (PT) was measured in the whole blood samples. Parameters of lipid status, as well as susceptibility to copper-induced oxidation of LDL particles
in vitro
were also determined. There was a significant reduction in total cholesterol and LDL-C only in the control group at the end of the study. No significant differences were observed in the remainder of the assessed parameters along the study. In conclusion, tomato juice may have favorable effects on lipid metabolism, but polyphenol fortification does not constitute additional beneficial cardiovascular effects.
The objective of this prospective study was to evaluate whether soluble programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) and serum amyloid A1 (SAA1) are potential diagnostic, ...predictive or prognostic biomarkers in lung cancer.
Lung cancer patients (n=115) with advanced metastatic disease, 101 with non-small cell lung cancer, NSCLC (77 EGFR wild-type NSCLC patients on chemotherapy, 15 EGFR mutation positive adenocarcinoma patients, 9 patients with mPD-L1 Expression ≥50% NSCLC - responders to immunotherapy), and 14 patients with small cell lung cancer (SCLC) were examined. ELISA method was used to determine sPD-L1 and SAA1 concentrations in patients' plasma.
Significantly higher blood concentrations of sPD-L1 and SAA1 were noted in lung cancer patients compared with a healthy control group. In PD-L1+ NSCLC patients, a significantly higher sPD-L1 level was noticed compared to any other lung cancer subgroup, as well as the highest average SAA1 value compared to other subgroups.
It seems that sPD-1/PD-L1 might be a potential biomarker, prognostic and/ or predictive, particularly in patients treated with immunotherapy. Serum amyloid A1 has potential to act as a good predictor of patients' survival, as well as a biomarker of a more advanced disease, with possibly good capability to predict the course of disease measured at different time points.
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