STUDY OF POSSIBLE MECHANISMS OF ACTOPROTECTIVE ACTION OF СATEKHIN HYDRATE

A study was carried out to study the possible mechanisms of actoprotective action of catechin hydrate administered at a dosage of 100 mg/kg. The animals were subjected to daily exhausting loads in the forced swimming test with a load of 10% of the animal's weight. After the end of the experiment, the rats were decapitated under chloral hydrate anesthesia (350 mg/kg) and the skeletal muscle was taken to obtain the supernatant. Using the ELISA method, the concentrations of nitric oxide isoforms (eNOS, iNOS, nNOS), PPAR (peroxisome proliferator-activated receptors) and JNK were estimated. It was found that against the background of the introduction of the test substance, an increase in eNOS activity was observed by 48.7% (p <0.05) relative to the group of negative control rats, as well as a decrease in iNOS and JNK — 1.9 times (p <0.05). In comparison with the group receiving Metaprot®, the concentration of endothelial synthase in the group receiving catechin hydrate was 1.3 times higher (p <0.05). The experiment performed suggests that the actoprotective effect of catechin hydrate is likely to be associated with inhibition of pathways mediated by JNK, activation of PPAR receptors, and the effect of these compounds on NO isoforms.

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Refinement of anesthetic choice in procedures preceding psychopharmacological studies

10.1101/390583 ◽

2018 ◽

Author(s):

LS Herbst ◽

T Gaigher ◽

AA Siqueira ◽

SRL Joca ◽

KN Sampaio ◽

...

Keyword(s):

Chloral Hydrate ◽

Forced Swimming Test ◽

Elevated Plus Maze ◽

General Anesthetics ◽

Single Exposure ◽

Experimental Conditions ◽

Plus Maze ◽

Swimming Test ◽

Per Se

AbstractRationalePrevious studies indicated that some general anesthetics induce long-term antidepressant and/or anxiolytic-like effects. This raises the concern about the use of anesthesia in surgeries that precede psycopharmacological tests, since it may be a potential bias on results depending on the experimental design used.ObjectivesTo evaluate whether commonly used general anesthetics in surgeries preceding psychopharmacological tests would affect rat behavior in tests predictive of antidepressant or anxiolytic-like effects. We also evaluated whether prior anesthesia would interfere in the detection of the antidepressant-like effect of imipramine or the anxiolytic-like effect of diazepam.MethodsWe tested if a single exposure to subanesthetic or anesthetic doses of 2,2,2-tribromoethanol, chloral hydrate, thiopental or isoflurane would change rat’s behavior in the forced swimming test (FST) or in the elevated plus-maze (EPM) test, at 2 hours or 7 days after administration.ResultsPrevious anesthesia with the aforementioned anesthetics did not change rat behavior in FST per se nor it changed the antidepressant-like effect induced by imipramine treatment. Rats previously anesthetized with tribromoethanol or chloral hydrate exhibited, respectively, anxiogenic-like or anxiolytic-like behavior in the EPM. Prior anesthesia with thiopental or isoflurane did not produce anyper seeffect in rat behavior in the EPM nor disturbed the anxiolytic-like effect of diazepam.ConclusionOur results suggest that, in our experimental conditions, tribromoethanol and chloral hydrate are improper anesthetics for surgeries that precede behavioral tests related to anxiety. Isoflurane or thiopental may be suitable for anesthesia before evaluation in animal models predictive of antidepressant or anxiolytic-like effect.

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Subtle Impact of Akt1 and Akt3 on Exploratory Behavior in Gene Targeted Mice

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000218 ◽

2015 ◽

Vol 223 (3) ◽

pp. 173-180 ◽

Cited By ~ 1

Author(s):

Christina Leibrock ◽

Michael Hierlmeier ◽

Undine E. Lang ◽

Florian Lang

Keyword(s):

Forced Swimming Test ◽

Open Field Test ◽

Wild Type ◽

Average Speed ◽

Closed Area ◽

Light Area ◽

Swimming Test ◽

The Impact ◽

Center Area ◽

Dark Transition

Abstract. The present study explored the impact of Akt1 and Akt3 on behavior. Akt1 (akt1-/-) and Akt3 (akt3-/-) knockout mice were compared to wild type (wt) mice. The akt1-/- mice, akt3-/- mice, and wt mice were similar in most parameters of the open-field test. However, the distance traveled in the center area was slightly but significantly less in akt3-/- mice than in wt mice. In the light/dark transition test akt1-/- mice had significantly lower values than wt mice and akt3-/- mice for distance traveled, number of rearings, rearing time in the light area, as well as time spent and distance traveled in the entrance area. They were significantly different from akt3-/- mice in the distance traveled, visits, number of rearings, rearing time in the light area, as well as time spent, distance traveled, number of rearings, and rearing time in the entrance area. In the O-maze the time spent, and the visits to open arms, as well as the number of protected and unprotected headdips were significantly less in akt1-/- mice than in wt mice, whereas the time spent in closed arms was significantly more in akt1-/- mice than in wt mice. Protected and unprotected headdips were significantly less in akt3-/- mice than in wt mice. In closed area, akt3-/- mice traveled a significantly larger distance at larger average speed than akt1-/- mice. No differences were observed between akt1-/- mice, akt3-/- mice and wt-type mice in the time of floating during the forced swimming test. In conclusion, akt1-/- mice and less so akt3-/ mice display subtle changes in behavior.

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Experimental anxiety-depressive state in rats caused by neonatal exposure to the inhibitor of dipeptidyl peptidase IV, diprotin A: effects of imipramine

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/igpp.2017.4.8517 ◽

2017 ◽

pp. 4-12

Author(s):

Н.Н. Хлебникова ◽

Н.А. Крупина

Keyword(s):

Forced Swimming Test ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Forced Swimming ◽

Face Validity ◽

Neonatal Exposure ◽

Depressive State ◽

Serum Corticosterone ◽

Old Rats ◽

Swimming Test

В наших предыдущих исследованиях было показано, что ингибитор пролинспецифической пептидазы дипептидилпептидазы-IV (ДП-IV, EC 3.4.14.5) трипептид дипротин А, введенный крысам в 5-18 постнатальные дни, приводит к развитию у крыс подросткового возраста и взрослых животных эмоционально-мотивационных расстройств. Такие расстройства можно рассматривать как модель смешанного тревожно-депрессивного состояния. Однако специальных исследований по валидности данной модели проведено не было. Цель настоящей работы состояла в проверке влияния трициклического антидепрессанта имипрамина (ИМИ) на депрессивноподобное поведение крыс и уровень кортикостерона в сыворотке крови животных на модели смешанного тревожно-депрессивного состояния. Методика. У крыс в возрасте одного и двух мес. определяли уровень тревожности в автоматизированном тесте «Приподнятый крестообразный лабиринт» и оценивали депрессивноподобное поведение в тесте принудительного плавания. ИМИ вводили взрослым животным в течение 10 дней (20 мг/кг/день, интрагастрально). Уровень кортикостерона в сыворотке крови определяли методом твердофазного иммуноферментного анализа. Результаты. Неонатальное действие дипротина А приводило к повышению тревожности у крыс в возрасте 1 мес. Депрессивноподобное поведение обнаружено у животных в возрасте одного и двух мес. ИМИ нормализовал поведение животных в тесте принудительного плавания и снижал уровень кортикостерона в сыворотке крови крыс. Кроме того, ИМИ снижал вес крыс. Заключение. Результаты исследования свидетельствуют в пользу адекватности модели смешанного тревожно-депрессивного расстройства, возникающего у крыс вследствие действия ингибитора ДП-IV дипротина А на второй-третьей неделях постнатального развития, клиническому прообразу заболевания по критериям «внешней схожести», прогностической и конструкционной валидности. Previously, we have shown that the inhibitor of proline-specific peptidase, dipeptidyl peptidase-IV (DP-IV, EC 3.4.14.5), tripeptide diproptin A administered on postnatal days 5-18 induced emotional and motivational disorders in adolescent and adult rats. These disorders can be considered a model of a mixed anxiety-depression-like disorder. However, validation studies of this model are not available. The aim of this work was to test the effect of the tricyclic antidepressant, imipramine (IMI), on depressive-like behavior in rats and the level of serum corticosterone using the model of mixed anxiety-depressive state. Methods. The level of anxiety was assessed by the automated Elevated Plus Maze test and the depressive-like behavior was evaluated by the forced swimming test in one- and two-month old rats. IMI was administered to adult animals for ten days (20 mg/kg a day, intragastrically). Serum corticosterone concentrations were measured using ELISA. Results. The neonatal exposure to diprotin A increased anxiety in one-month old rats. The depressive-like behavior was observed in animals aged one and two months. IMI normalized behavior of animals in the forced swimming test and reduced serum levels of corticosterone. Also, IMI reduced body weight of rats. Conclusion. The results of the study evidenced adequacy of the model of mixed anxiety-depressive state induced by the DP-IV inhibitor, diprotin A, on the second and third postnatal weeks to the clinical prototype of disease according to criteria of face validity, predictive and construct validity.

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New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

Current Medicinal Chemistry ◽

10.2174/1570162x18666201123114934 ◽

2020 ◽

Vol 28 ◽

Author(s):

Seyed Mohammad Nabavi ◽

Kasi Pandima Devi ◽

Sethuraman Sathya ◽

Ana Sanches-Silva ◽

Listos Joanna ◽

...

Keyword(s):

Tissue Expression ◽

Health Concern ◽

Pharmacological Intervention ◽

Peroxisome Proliferator ◽

Expression Of Genes ◽

Ppar Agonists ◽

Prevalence Of Obesity ◽

Peroxisome Proliferator Activated Receptors ◽

Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

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Keratinocyte aquaporin‐3 expression induced by histone deacetylase inhibitors is mediated in part by peroxisome proliferator‐activated receptors (PPARs)

Experimental Dermatology ◽

10.1111/exd.14080 ◽

2020 ◽

Vol 29 (4) ◽

pp. 380-386 ◽

Cited By ~ 2

Author(s):

Rong Yang ◽

Shinjini Chowdhury ◽

Vivek Choudhary ◽

Xunsheng Chen ◽

Wendy B. Bollag

Keyword(s):

Histone Deacetylase ◽

Histone Deacetylase Inhibitors ◽

Peroxisome Proliferator ◽

Aquaporin 3 ◽

Peroxisome Proliferator Activated Receptors

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Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽

10.3390/cells10030629 ◽

2021 ◽

Vol 10 (3) ◽

pp. 629

Author(s):

Jorge Gutiérrez-Cuevas ◽

Ana Sandoval-Rodriguez ◽

Alejandra Meza-Rios ◽

Hugo Christian Monroy-Ramírez ◽

Marina Galicia-Moreno ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Dysfunction ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Peroxisome Proliferator ◽

White Adipocyte ◽

Peroxisome Proliferator Activated Receptors ◽

And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

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Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.16.29 ◽

2020 ◽

Vol 16 ◽

pp. 297-304 ◽

Cited By ~ 1

Author(s):

Amit Raj Sharma ◽

Enjuro Harunari ◽

Naoya Oku ◽

Nobuyasu Matsuura ◽

Agus Trianto ◽

...

Keyword(s):

Fatty Acids ◽

Spectroscopic Analysis ◽

Culture Broth ◽

Peroxisome Proliferator ◽

Simulation Studies ◽

Fish Pathogen ◽

Chemical Structures ◽

Agonistic Activity ◽

Isoform Specificity ◽

Peroxisome Proliferator Activated Receptors

A pair of geometrically isomeric unsaturated keto fatty acids, (6E,8Z)- and (6E,8E)-5-oxo-6,8-tetradecadienoic acids (1 and 2), were isolated from the culture broth of an actinomycete of the genus Micrococcus, which was associated with a stony coral, Catalaphyllia sp. Their chemical structures were elucidated by spectroscopic analysis including NMR and MS, with special assistance of spin system simulation studies for the assignment of an E geometry at C8 in 2. As metabolites of microbes, compounds 1 and 2 are unprecedented in terms of bearing a 2,4-dienone system. Both 1 and 2 showed antibacterial activity against the plant pathogen Rhizobium radiobacter and the fish pathogen Tenacibaculum maritimum, with a contrasting preference that 1 is more effective to the former strain while 2 is so to the latter. In addition, compounds 1 and 2 displayed agonistic activity against peroxisome proliferator-activated receptors (PPARs) with an isoform specificity towards PPARα and PPARγ.

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