scholarly journals Investigation of betaine as a novel psychotherapeutic for schizophrenia

2019 ◽  
Author(s):  
Tetsuo Ohnishi ◽  
Shabeesh Balan ◽  
Manabu Toyoshima ◽  
Motoko Maekawa ◽  
Hisako Ohba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Behavioral Sensitization ◽  
Inbred Mice ◽  
Causal Link ◽  
Carbonyl Stress ◽  
Proinflammatory Responses ◽  
Postmortem Brains ◽  
Trait Locus ◽  
Deficient Mice

ABSTRACTBetaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine treatments. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with “betaine deficit-oxidative stress pathology”. We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-defícient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. In conclusion, the present study underscores the potential benefit of betaine in a subset of schizophrenia.

scholarly journals The influence of natural dicarbonils on the antioxidant enzymes activity in vitro and in vivo

2012 ◽  
Vol 58 (6) ◽  
pp. 727-736 ◽  
Author(s):  
V.Z. Lankin ◽  
G.G. Konovalova ◽  
A.K. Tikhaze ◽  
L.V. Nedosugova
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Antioxidant Enzymes ◽  
Carbonyl Stress ◽  
Diabetic Patients ◽  
Glutathione S Transferase ◽  
Liver Glutathione ◽  
Bovine Erythrocytes

Natural dicarbonyls, which may be accumulated during oxidative stress in atherosclerosis (e.g. malondialdehyde) or carbonyl stress in diabetes mellitus (glyoxal and methylglyoxal) effectively inhibited the activities of commercial preparations of antioxidant enzymes: catalase, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Se-contained glutathione peroxidase from human and bovine erythrocytes and also rat liver glutathione-S-transferase. After incubation of human erythrocytes with 10 mM of each investigated dicarbonyls the decrease of intracellular Cu,Zn-SOD was observed. The decreased activity of erythrocyte Cu,Zn-SOD was also detected in diabetic patients with carbohydrate metabolism disturbance but effective sugar-lowered therapy was accompanied by the increase of this enzyme activity. The increase of erythrocytes activity of Cu,Zn-SOD of diabetic patients theated with metformin (which may utilize methylglyoxal) was higher than in erythrocytase of diabetic patients subjected to traditional therapy.

scholarly journals Inhibition of Phosphodiesterase 3A by Cilostazol Dampens Proinflammatory Platelet Functions

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1998
Author(s):  
Daniëlle M. Coenen ◽  
Alexandra C. A. Heinzmann ◽  
Silvia Oggero ◽  
Hugo J. Albers ◽  
Magdolna Nagy ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Ex Vivo ◽  
Pde5 Inhibitor ◽  
Human Platelets ◽  
Type I ◽  
Proinflammatory Responses ◽  
Coronary Syndromes ◽  
Deficient Mice ◽  
Platelet Functions

Objective: platelets possess not only haemostatic but also inflammatory properties, which combined are thought to play a detrimental role in thromboinflammatory diseases such as acute coronary syndromes and stroke. Phosphodiesterase (PDE) 3 and -5 inhibitors have demonstrated efficacy in secondary prevention of arterial thrombosis, partially mediated by their antiplatelet action. Yet it is unclear whether such inhibitors also affect platelets’ inflammatory functions. Here, we aimed to examine the effect of the PDE3A inhibitor cilostazol and the PDE5 inhibitor tadalafil on platelet function in various aspects of thromboinflammation. Approach and results: cilostazol, but not tadalafil, delayed ex vivo platelet-dependent fibrin formation under whole blood flow over type I collagen at 1000 s−1. Similar results were obtained with blood from Pde3a deficient mice, indicating that cilostazol effects are mediated via PDE3A. Interestingly, cilostazol specifically reduced the release of phosphatidylserine-positive extracellular vesicles (EVs) from human platelets while not affecting total EV release. Both cilostazol and tadalafil reduced the interaction of human platelets with inflamed endothelium under arterial flow and the release of the chemokines CCL5 and CXCL4 from platelets. Moreover, cilostazol, but not tadalafil, reduced monocyte recruitment and platelet-monocyte interaction in vitro. Conclusions: this study demonstrated yet unrecognised roles for platelet PDE3A and platelet PDE5 in platelet procoagulant and proinflammatory responses.

scholarly journals Characterization of the Age-Dependent Changes in Antioxidant Defenses and Protein’s Sulfhydryl/Carbonyl Stress in Human Follicular Fluid

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 927
Author(s):  
Alice Luddi ◽  
Laura Governini ◽  
Angela Capaldo ◽  
Giovanna Campanella ◽  
Vincenzo De Leo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Follicular Fluid ◽  
Structural Changes ◽  
Early Embryo ◽  
Antioxidant Defenses ◽  
Carbonyl Stress ◽  
2D Electrophoresis ◽  
Human Follicular Fluid ◽  
Vitro Fertilization

The oxidative stress, characterized by the imbalance between pro-oxidants and antioxidants molecules, seems to be involved in the pathogenesis of female subfertility. In particular, the presence of different markers of oxidative stress has been reported in human follicular fluid (FF) surrounding oocytes. Based on its distinctive composition and on the close proximity to the oocyte, FF creates a unique microenvironment having a direct impact on oocyte quality, implantation, and early embryo development. An imbalance in reactive oxygen species (ROS) production in ovarian follicular fluid may have a negative effect on these processes and, as a consequence, on female fertility. Therefore, the aim of this study was to evaluate the redox state of the FF through various methodological approaches. By means of 2D-electrophoresis we demonstrated that the main structural changes occurring in the proteins of the follicular fluid of normovulatory women were correlated to the age of the patients and to the antioxidant defenses present in the FF. Measurement of these parameters could have clinical relevance, since the assessment of the oxidative stress rate may be helpful in evaluating in vitro fertilization potential.

Multinucleated Osteoclast Formation In Vivo and In Vitro by P2X7 Receptor-Deficient Mice

2003 ◽  
Vol 13 (2-4) ◽  
pp. 12 ◽  
Author(s):  
Alison Gartland ◽  
Katherine A. Buckley ◽  
Robert A. Hipskind ◽  
M. J. Perry ◽  
J. H. Tobias ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Osteoclast Formation ◽  
Deficient Mice

Interactions Between Dental Composite Resins and Saliva A comparative biochemical in vitro study

2019 ◽  
Vol 56 (3) ◽  
pp. 529-533
Author(s):  
Mihaela Pantea ◽  
Diana Andreea Ighigeanu ◽  
Alexandra Totan ◽  
Maria Greabu ◽  
Daniela Miricescu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Vitro Study ◽  
Composite Resins ◽  
Vitro Study ◽  
Dental Composite ◽  
Gamma Glutamyl Transferase ◽  
Specific Protocol ◽  
Dental Composite Resins ◽  
Glutamyl Transferase

This in vitro study analyses the biochemical interaction between saliva and three types of dental composite resins (a direct resin, an indirect resin and a dual-cure resin used for cementation of indirect dental restorations). The resin samples were obtained following a specific protocol and in line with the producers� recommendations; the resin samples were incubated with saliva samples collected from 19 healthy volunteers. The obtained results showed that the tested composite resins did not produce significant changes in oxidative stress parameters that were analysed (albumin, uric acid, GGT / gamma glutamyl transferase, OXSR-1 / oxidative stress responsive kinase 1) and do not influence the inflammatory salivary status reflected by the levels of IL-6 - an inflammatory marker.

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