In this study, we focused on comparing the effects of serotonin and its metabolites on the functions of RAW264.7 cells (emphasis on oxidative burst and production of nitric oxide and cytokines), thereby expanding the scope of existing knowledge with advent of novel findings in this field. Changes in production of reactive oxygen species (ROS) by RAW264.7 cells after treatment with serotonin, N-acetylserotonin and melatonin were determined using the chemiluminescence (CL) assay. To exclude the direct scavenging effects of the studied compounds on the CL response, the antioxidant properties of all respective compounds were measured using TRAP and amperometrical method. Nitric oxide (NO) production was measured by Griess reagent and inducible NO synthase (iNOS) expression by Western blot. Cytokine production was assessed using the Mouse Cytokine Panel A Array kit and ELISA. We showed that all tested compounds were able to reduce oxidative stress, as well as inhibit production of inflammatory cytokines by macrophages. Of the tested compounds, serotonin and N-acetylserotonin were markedly better antioxidants than melatonin. In comparison, other effects of tested compounds were very similar. It can be concluded that antioxidant capacity of tested compounds is a major advantage in the early stages of inflammation. Since plasma concentrations of N-acetylserotonin and melatonin are lower than serotonin, it can be deduced that serotonin plays a key role in modulation of inflammation and the regulatory functions of immune cells, while also protecting cells against oxidative stress.
- MeSH
- antioxidancia farmakologie MeSH
- cytokiny metabolismus MeSH
- makrofágy metabolismus MeSH
- melatonin farmakologie MeSH
- myši MeSH
- oxid dusnatý metabolismus MeSH
- oxidační stres účinky léků MeSH
- RAW 264.7 buňky MeSH
- reaktivní formy kyslíku metabolismus MeSH
- serotonin analogy a deriváty farmakologie MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.
- MeSH
- arachidonátlipoxygenasy genetika metabolismus MeSH
- artritida experimentální farmakoterapie genetika patologie MeSH
- biologické markery MeSH
- C-reaktivní protein MeSH
- časové faktory MeSH
- cytokiny krev genetika metabolismus MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- mediátory zánětu * MeSH
- methotrexát farmakologie MeSH
- modely nemocí na zvířatech MeSH
- orgánová specificita MeSH
- regulace genové exprese účinky léků MeSH
- serotonin analogy a deriváty farmakologie MeSH
- stupeň závažnosti nemoci MeSH
- transkriptom * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.
- MeSH
- amidohydrolasy antagonisté a inhibitory genetika metabolismus MeSH
- chování zvířat účinky léků MeSH
- endokanabinoidy metabolismus MeSH
- fyzické omezení MeSH
- glyceridy metabolismus MeSH
- kationtové kanály TRPV antagonisté a inhibitory genetika metabolismus MeSH
- kortikosteron krev MeSH
- krysa rodu rattus MeSH
- kyseliny arachidonové metabolismus farmakologie terapeutické užití MeSH
- mozek účinky léků metabolismus MeSH
- mozkový neurotrofický faktor genetika metabolismus MeSH
- plavání MeSH
- polynenasycené alkamidy metabolismus MeSH
- potkani Wistar MeSH
- psychický stres krev farmakoterapie metabolismus MeSH
- serotonin analogy a deriváty farmakologie terapeutické užití MeSH
- systém hypofýza - nadledviny MeSH
- systém hypotalamus-hypofýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The effects of N-feruloylserotonins, substances isolated from the seeds of Leuzea carthamoides (WILLD.) DC., on nociception and anxiety were studied in Wistar rats. Nociceptive responses were measured using the plantar and tail-flick tests which were administered before and after swimming stress (3 min, water temperature 32 degrees C). Anxiety was evaluated using an elevated plus maze. In Experiment I, neither basal nociception nor stress-induced analgesia was influenced significantly. Separating the animals into groups based on their basal nociceptive sensitivity, either high- or low-pain threshold revealed that N-feruloylserotonins have selective effects, especially on rats with high-pain thresholds. In these animals, N-feruloylserotonins reduced the stress-induced analgesia that followed swimming stress. In Experiment II, basal nociceptive sensitivity correlated with indicators of anxiety; high-pain threshold rats were more anxious in the elevated plus maze, with less frequent visits to open arms. The opposite effect was seen in low-pain threshold rats. N-feruloylserotonins did not influence anxiety in low-pain threshold rats, although it reduced anxiety in the high-pain threshold rats as indicated by the increased ratio of open arm visit frequency compared to closed arm visit frequency in the elevated plus maze. From these results we concluded that N-feruloylserotonins have selective stress-reducing effects in stress-sensitive animals.
- MeSH
- analgetika MeSH
- anxiolytika MeSH
- financování organizované MeSH
- krysa rodu rattus MeSH
- Leuzea chemie MeSH
- měření bolesti účinky léků MeSH
- plavání psychologie MeSH
- potkani Wistar MeSH
- práh bolesti účinky léků MeSH
- psychický stres psychologie MeSH
- reakční čas účinky léků MeSH
- serotonin analogy a deriváty farmakologie izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie MeSH
- adjuvancia imunologická farmakologie MeSH
- ileum fyziologie účinky léků MeSH
- metergolin farmakologie MeSH
- receptory serotoninové účinky léků MeSH
- serotonin analogy a deriváty farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- antagonisté serotoninu farmakologie MeSH
- hladké svalstvo chemie účinky léků MeSH
- kolon chemie účinky léků MeSH
- morčata MeSH
- receptory serotoninové fyziologie MeSH
- relaxace svalu účinky léků MeSH
- serotonin analogy a deriváty farmakologie MeSH
- techniky in vitro MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Klíčová slova
- IMIGRAN,
- MeSH
- lidé MeSH
- migréna etiologie farmakoterapie MeSH
- receptory serotoninové MeSH
- serotonin analogy a deriváty MeSH
- vazokonstriktory MeSH
- Check Tag
- lidé MeSH
