In today's modern society, it seems to be more and more challenging to cope with life stresses. The effect of psychological stress on emotional and physical health can be devastating, and increased stress is associated with increased rates of heart attack, hypertension, obesity, addiction, anxiety and depression. This review focuses on the possibility of an influence of psychological stress on the metabolism of selected antidepressants (TCAs, SSRIs, SNRIs, SARIs, NDRIs a MMAs) and anxiolytics (benzodiazepines and azapirone), as patients treated with antidepressants and/or anxiolytics can still suffer from psychological stress. Emphasis is placed on the drug metabolism mediated by the enzymes of Phase I, typically cytochromes P450 (CYPs), which are the major enzymes involved in drug metabolism, as the majority of psychoactive substances are metabolized by numerous CYPs (such as CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2A6, CYP2D6, CYP3A4). As the data on the effect of stress on human enzymes are extremely rare, modulation of the efficacy and even regulation of the biotransformation pathways of drugs by psychological stress can be expected to play a significant role, as there is increasing evidence that stress can alter drug metabolism, hence there is a risk of less effective drug metabolism and increased side effects.

• Klíčová slova
• antidepressants, anxiolytics, cytochrome P450, drug metabolism, psychological stress,
• MeSH
• antidepresiva metabolismus   MeSH
• anxiolytika * metabolismus   MeSH
• biotransformace MeSH
• jaterní mikrozomy metabolismus   MeSH
• lidé MeSH
• psychický stres MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antidepresiva MeSH
• anxiolytika * MeSH
• systém (enzymů) cytochromů P-450 MeSH

The gut microbiota is involved in a number of different metabolic processes of the host organism, including the metabolism of xenobiotics. In our study, we focused on liver cytochromes P450 (CYPs), which can metabolize a wide range of exo- and endogenous molecules. We studied changes in mRNA expression and CYP enzyme activities, as well as the mRNA expression of transcription factors that have an important role in CYP expression, all in stressed germ-free (GF) and stressed specific-pathogen-free (SPF) mice. Besides the presence of the gut microbiota, we looked at the difference between acute and chronic stress. Our results show that stress has an impact on CYP mRNA expression, but it is mainly chronic stress that has a significant effect on enzyme activities along with the gut microbiome. In acutely stressed mice, we observed significant changes at the mRNA level, however, the corresponding enzyme activities were not influenced. Our study suggests an important role of the gut microbiota along with chronic psychosocial stress in the expression and activity of CYPs, which can potentially lead to less effective drug metabolism and, as a result, a harmful impact on the organism.

• MeSH
• játra enzymologie   mikrobiologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• psychický stres * MeSH
• regulace genové exprese enzymů MeSH
• střevní mikroflóra fyziologie   MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• xenobiotika metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• systém (enzymů) cytochromů P-450 MeSH
• transkripční faktory MeSH
• xenobiotika MeSH

Gadolinium (Gd)-based contrast agents are extensively used for magnetic resonance imaging (MRI). Liposomes are potential nanocarrier-based biocompatible platforms for development of new generations of MRI diagnostics. Liposomes with Gd-complexes (Gd-lip) co-encapsulated with thrombolytic agents can serve both for imaging and treatment of various pathological states including stroke. In this study, we evaluated nanosafety of Gd-lip containing PE-DTPA chelating Gd+3 prepared by lipid film hydration method. We detected no cytotoxicity of Gd-lip in human liver cells including cancer HepG2, progenitor (non-differentiated) HepaRG, and differentiated HepaRG cells. Furthermore, no potential side effects of Gd-lip were found using a complex system including general biomarkers of toxicity, such as induction of early response genes, oxidative, heat shock and endoplasmic reticulum stress, DNA damage responses, induction of xenobiotic metabolizing enzymes, and changes in sphingolipid metabolism in differentiated HepaRG. Moreover, Gd-lip did not show pro-inflammatory effects, as assessed in an assay based on activation of inflammasome NLRP3 in a model of human macrophages, and release of eicosanoids from HepaRG cells. In conclusion, this in vitro study indicates potential in vivo safety of Gd-lip with respect to hepatotoxicity and immunopathology caused by inflammation.

• MeSH
• diethylentriaminpentaacetát gadolinia * škodlivé účinky   toxicita   MeSH
• fibrinolytika MeSH
• fosfatidylethanolaminy * škodlivé účinky   toxicita   MeSH
• hepatocyty účinky léků   MeSH
• inflamasomy MeSH
• kontrastní látky * MeSH
• kultivované buňky MeSH
• lidé MeSH
• liposomy * MeSH
• magnetická rezonanční tomografie * MeSH
• makrofágy účinky léků   MeSH
• nanočástice MeSH
• nosiče léků * MeSH
• protein NLRP3 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• diethylentriaminpentaacetát gadolinia * MeSH
• fibrinolytika MeSH
• fosfatidylethanolaminy * MeSH
• gadolinium phosphatidylethanolamine-DTPA MeSH Prohlížeč
• inflamasomy MeSH
• kontrastní látky * MeSH
• liposomy * MeSH
• NLRP3 protein, human MeSH Prohlížeč
• nosiče léků * MeSH
• protein NLRP3 MeSH