AIM: Widely used second-generation antipsychotics are associated with adverse metabolic effects, contributing to increased cardiovascular mortality. To develop strategies to prevent or treat adverse metabolic effects, preclinical models have a clear role in uncovering underlying molecular mechanisms. However, with few exceptions, preclinical studies have been performed in healthy animals, neglecting the contribution of dysmetabolic features inherent to psychotic disorders. METHODS: In this study, methylazoxymethanol acetate (MAM) was prenatally administered to pregnant Sprague-Dawley rats at gestational day 17 to induce a well-validated neurodevelopmental model of schizophrenia mimicking its assumed pathogenesis with persistent phenotype. Against this background, the dysmetabolic effects of acute treatment with olanzapine and haloperidol were examined in female rats. RESULTS: Prenatally MAM-exposed animals exhibited several metabolic features, including lipid disturbances. Half of the MAM rats exposed to olanzapine had pronounced serum lipid profile alteration compared to non-MAM controls, interpreted as a reflection of a delicate MAM-induced metabolic balance disrupted by olanzapine. In accordance with the drugs' clinical metabolic profiles, olanzapine-associated dysmetabolic effects were more pronounced than haloperidol-associated dysmetabolic effects in non-MAM rats and rats exposed to MAM. CONCLUSION: Our results demonstrate metabolic vulnerability in female prenatally MAM-exposed rats, indicating that findings from healthy animals likely provide an underestimated impression of metabolic dysfunction associated with antipsychotics. In the context of metabolic disturbances, neurodevelopmental models possess a relevant background, and the search for adequate animal models should receive more attention within the field of experimental psychopharmacology.
- MeSH
- antipsychotika * terapeutické užití MeSH
- haloperidol * toxicita MeSH
- krysa rodu rattus MeSH
- lipidy MeSH
- methylazoxymethanolacetát toxicita analogy a deriváty MeSH
- modely nemocí na zvířatech MeSH
- olanzapin toxicita MeSH
- potkani Sprague-Dawley MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This work presents a deeper pharmacological evaluation of two formerly prepared and characterized, and highly in vitro cytotoxic platinum(II) oxalato complexes [Pt(ox)(L1)2] (1) and [Pt(ox)(L2)2] (2), containing the derivatives of cyclin-dependent kinase inhibitor (CDKi) seliciclib ((R)-roscovitine, CYC202) coordinating as N-donor carrier ligands, i.e., 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L1) and 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L2). The positive results of in vitro cytotoxicity screening on human cancer cell lines (HeLa, HOS, A2780, A2780R, G361 and MCF7 with IC50 at low micromolar levels) published previously, motivated us to perform extended preclinical in vitro experiments to reveal the mechanisms associated with the induction of cancer cell death. In addition, the in vivo antitumor activity was evaluated using the mouse lymphocytic leukaemia L1210 model. The obtained results revealed that complex 1 exceeds the antitumor effect of cisplatin (as for the extension of life-span of mice) and shows far less adverse effects as compared to reference drug cisplatin. The in vitro and ex vivo studies of cellular effects and molecular mechanisms of cell death induction showed that the mechanism of action of complex 1 is essentially different from that of cisplatin. The obtained results showed a possible way how to obtain antitumor active platinum(II) oxalato complexes with better therapeutic profile than contemporary used platinum-based therapeutics.
- MeSH
- apoptóza účinky léků MeSH
- cisplatina škodlivé účinky MeSH
- lidé MeSH
- lymfom patologie MeSH
- myši inbrední DBA MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny chemie MeSH
- oxaláty chemie MeSH
- protinádorové látky chemie farmakologie MeSH
- roskovitin chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. is used in traditional Chinese medicine for the treatment of various diseases, including bacterial infections and inflammation. As a rich source of phenolic compounds, the plant is an object of many phytochemical and pharmacological studies. AIM OF THE STUDY: The aim of the study was to isolate and evaluate possible parallel antiviral, antibacterial, and anti-inflammatory activities of phenolic mulberry compounds. MATERIALS AND METHODS: Extensive chromatographic separation of mulberry root bark extract and in vitro biological screening of 26 constituents identified promising candidates for further pharmacological research. Selected compounds were screened for anti-infective and anti-inflammatory activities. Antiviral activity was determined by the plaque number reduction assay and by the titer reduction assay, antibacterial using broth microdilution method, and anti-inflammatory activity using COX Colorimetric inhibitor screening assay kit. One compound was evaluated in vivo in carrageenan-induced paw-edema in mice. RESULTS: Five prenylated compounds 1, 2, 8, 9, and 11, together with a simple phenolic ester 13, exhibited inhibitory activity against the replication of herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2), with IC50 values ranging from 0.64 to 1.93 μg/mL, and EC50 values 0.93 and 1.61 μg/mL. Molecular docking studies demonstrated the effects of the active compounds by targeting HSV-1 DNA polymerase and HSV-2 protease. In antibacterial assay, compounds 1, 4, 11, and 17 diminished the growth of all of the Gram-positive strains tested, with MIC values of 1-16 μg/mL. The anti-inflammatory ability of several compounds to inhibit cyclooxygenase 2 (COX-2) was tested in vitro, and compound 16 displayed greater activity than the indomethacin, positive control. Mulberrofuran B (11) showed anti-inflammatory activity in vivo against carrageenan-induced paw-edema in mice. CONCLUSIONS: Experimental investigation showed promising antiviral, antibacterial, and/or anti-inflammatory activities of the phenolic mulberry constituents, often with multiple inhibitory effects that might be used as a potential source of new medicine.
- MeSH
- buněčné linie MeSH
- diabetes mellitus farmakoterapie metabolismus MeSH
- glukosa metabolismus MeSH
- glykogen metabolismus MeSH
- hypoglykemika farmakologie terapeutické užití MeSH
- inzulinová rezistence MeSH
- játra účinky léků metabolismus MeSH
- kosterní svaly účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- listy rostlin MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- Morus * MeSH
- myši MeSH
- proteinkinasy aktivované AMP metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rostlinné extrakty farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Cíl: Vývoj nových léčiv a léčebných postupů se v současnosti bez zvířecích modelů neobejde. Vzhledem k unikátní komplexnosti CMP je počet modelů ji studujících neobvykle široký. Cílem přehledu je popsat a jednoduše analyzovat spektrum používaných experimentálních modelů a běžně používaných živočišných druhů ve výzkumu CMP. Metody: Publikace byly vyhledány v listopadu 2017 v databázích: PubMed, Science Direct, Wiley Online Library a Springer Link pomocí kombinace klíčových slov. U každého modelu CMP byl evidován typ modelu, druh zvířete, jeho pohlaví a věk a byla vyhodnocena četnost výskytu v sledovaných publikačních databázích. Vyloučeny byly nerelevantní publikace a duplicity. Výsledky: Z 26 198 článků bylo dohledáno 3 093 relevantních odkazů, které odpovídaly zadání metodologie. Výsledky byly zpracovány v přehledové tabulce. Závěr: Práce mapuje četnost použití animálních modelů a používaných živočišných druhů v problematice výzkumu CMP.
Aim: The development of new drugs and curative treatments without animal models is currently not possible. Due to the unique complexity of stroke, the number of models studying this is unusually extensive. The aim of the overview is to describe and simply analyse used experimental models and commonly used animal species in research in vascular events. Methods: The publications were searched in November 2017 in databases: PubMed, Science Direct, Wiley Online Library and Springer Link by using key word combinations. There was the registered type of model, species of animal, its gender and age of the animal for each stroke model, and there was the registered frequency of occurrence in monitored publication databases. Relevant publications and duplications were not excluded. Results: There were 3,093 relevant links from 26,198 articles, which correspond to the specification of the methodology. The results were processed in an overviewed table. Conclusion: The article maps the frequency of use of animal models and used animal species in the field of stroke research.
- MeSH
- cévní mozková příhoda * MeSH
- Gerbillinae MeSH
- kočky MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech * MeSH
- myši MeSH
- ovce MeSH
- prasata MeSH
- primáti MeSH
- psi MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- myši MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
