- Evaluation of the antianxiety and antidepressant activities of mosapride in Wistar albino rats. [Journal Article]
- JBJ Basic Clin Physiol Pharmacol 2019 Jul 18
- Background The 5HT4 receptor agonists are antidepressants with a unique mode of action. Many studies have been done on investigational drugs, and mosapride has been shown to have a 5HT3 antagonistic …
Background The 5HT4 receptor agonists are antidepressants with a unique mode of action. Many studies have been done on investigational drugs, and mosapride has been shown to have a 5HT3 antagonistic property. In this study, we assessed the potential anxiolytic and antidepressant effects of mosapride on Wistar albino rats. Methods The rats were randomly assigned to two models containing 4 groups of 6 animals each. In the anxiety model, four groups included 0.5 mL of 0.5% carboxymethyl cellulose (CMC), mosapride 1.5 mg/kg, mosapride 3 mg/kg and diazepam 2 mg/kg. They were dosed for 5 days. On the 3rd day, the elevated plus maze (EPM) was conducted, and on the 5th day, the open field (OF) tests were conducted. In the depression model, four groups included 0.5 mL of 0.5% CMC, mosapride 1.5 mg/kg, mosapride 3 mg/kg and imipramine 30 mg/kg. After 3 days of dosing, the forced swim test (FST) was conducted, followed by a washout period of 1 month. Then, the rats were subjected to chronic unpredictable stress with sucrose preference. Results Compared with the control, the mosapride-treated animals showed significant anxiolytic behavior at both high and low doses in the EPM and OF tests. In the FST, both high and low doses of mosapride reduced immobility. The climbing behavior was prominent at a high dose of mosapride, whereas swimming was prominent at a low dose. In the chronic stress model, both doses of mosapride preserved sucrose preference comparable to imipramine. Conclusion These findings suggest that mosapride has anxiolytic and antidepressant activities at clinically used doses.
- Optical Nanosensing of Lipid Accumulation due to Enzyme Inhibition in Live Cells. [Journal Article]
- ANACS Nano 2019 Jul 17
- Drugs that influence enzymes of lipid metabolism can cause pathological accumulation of lipids in animal cells. Here, gold nanoparticles, acting as nanosensors that deliver surface-enhanced Raman sca…
Drugs that influence enzymes of lipid metabolism can cause pathological accumulation of lipids in animal cells. Here, gold nanoparticles, acting as nanosensors that deliver surface-enhanced Raman scattering (SERS) spectra from living cells provide molecular evidence of lipid accumulation in lysosomes after treatment of cultured cells with the three tricyclic antidepressants (TCA), desipramine, amitryptiline, and imipramine, respectively. The vibrational spectra elucidate to a great detail, and with very high sensitivity the composition of the drug induced lipid accumulations, also observed in fixed samples by electron microscopy and X-ray nanotomography. The nanoprobes show that mostly sphingomyelin is accumulated in the lysosomes, but also other lipids, in particular cholesterol. The observation of sphingomyelin accumulation supports the impairment of the enzyme acid sphingomyelinase. The SERS data were analyzed by random forest (RF) based approaches, in particular by minimal depth (MD) variable selection and surrogate minimal depth (SMD), shown here to be particularly useful machine learning tools for the analysis of the lipid signals that contribute only weakly to SERS spectra of cells. SMD is used for the identification of molecular co-localization and interactions of the drug molecules with lipid membranes and for discriminating between the biochemical effects of the three different TCA molecules, in agreement with their different activity. The spectra also indicate that the protein composition is significantly changed in cells treated with the drugs.
- Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies. [Journal Article]
- AApoptosis 2019 Jul 05
- Depression is a serious medical condition, typically treated by antidepressants. Conventional monotherapy can be effective only in 60-80% of patients, thus modern psychiatry deals with the challenge …
Depression is a serious medical condition, typically treated by antidepressants. Conventional monotherapy can be effective only in 60-80% of patients, thus modern psychiatry deals with the challenge of new methods development. At the same moment, interactions between antidepressants and the occurrence of potential side effects raise serious concerns, which are even more exacerbated by the lack of relevant data on exact molecular mechanisms. Therefore, the aims of the study were to provide up-to-date information on the relative mechanisms of action of single antidepressants and their combinations. In this study, we evaluated the effect of single and combined antidepressants administration on mouse hippocampal neurons after 48 and 96 h in terms of cellular and biochemical features in vitro. We show for the first time that co-treatment with amitriptyline/imipramine + fluoxetine initiates in cells adaptation mechanisms which allow cells to adjust to stress and finally exerts less toxic events than in cells treated with single antidepressants. Antidepressants treatment induces in neuronal cells oxidative and nitrosative stress, which leads to micronuclei and double-strand DNA brakes formation. At this point, two different mechanistic events are initiated in cells treated with single and combined antidepressants. Single antidepressants (amitriptyline, imipramine or fluoxetine) activate cell cycle arrest resulting in proliferation inhibition. On the other hand, treatment with combined antidepressants (amitriptyline/imipramine + fluoxetine) initiates p16-dependent cell cycle arrest, overexpression of telomere maintenance proteins and finally restoration of proliferation. In conclusion, our findings may pave the way to better understanding of the stress-related effects on neurons associated with mono- and combined therapy with antidepressants.
- A non-toxic approach to assess total antioxidant capacity (TAC) of exotic tropical fruits from Thailand. [Journal Article]
- JFJ Food Sci Technol 2019; 56(7):3547-3552
- A simple flow injection analysis (FIA) integrating with a metal-free approach for total antioxidant capacity (TAC) was developed. The non-toxic reaction was based on generating a vibrant blue radical…
A simple flow injection analysis (FIA) integrating with a metal-free approach for total antioxidant capacity (TAC) was developed. The non-toxic reaction was based on generating a vibrant blue radical from imipramine to avoid the potential interferents arising from the colorful fruit extracts. The blue radical can be rapidly scavenged by antioxidant compounds present in the sample. TAC values of Thai tropical fruit extracts were assessed by monitoring the quenching in absorbance of the test mixture following the addition of the antioxidant compounds/fruit extracts. The FIA co-operated in order to increase the sample throughput. The results demonstrated that Antidesma thwaiteaianum Muell. Arg. has the highest capacity followed by Terminalia chebula Retz. and Phyllanthus Emblica Linn., respectively. An excellent correlation between the proposed method was found with the DPPH assay. The proposed method allowed the TAC determination of fruit extracts in a high-throughput and straightforward way in accordance with the principles of green analytical chemistry.
- Acid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity. [Journal Article]
- BloodBlood 2019 Jul 01
- Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of the coagulation. Typically, most of TF on cell surfaces exist in a cryptic, coagulant inactive state, but transf…
Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of the coagulation. Typically, most of TF on cell surfaces exist in a cryptic, coagulant inactive state, but transformed to a procoagulant form (decryption) following cell activation. Our recent studies in cell model systems showed that sphingomyelin (SM) in the outer leaflet of the plasma membrane is responsible for maintaining TF in an encrypted state in resting cells and the hydrolysis of SM leads to decryption of TF. The present study was carried out to investigate the relevance of this novel mechanism in the regulation of TF procoagulant activity in pathophysiology. As observed in cell systems, administration of ATP to mice enhanced LPS-induced TF procoagulant activity in monocytes. Treatment of mice with pharmacological inhibitors of ASMase, desipramine and imipramine, attenuated ATP-induced TF decryption. Interestingly, ASMase inhibitors also blocked LPS-induced TF procoagulant activity without affecting the LPS-induced de novo synthesis of TF protein. Additional studies showed that LPS induced translocation of ASMase to the outer leaflet of the plasma membrane and reduced SM levels in monocytes. Studies using human monocyte-derived macrophages and endothelial cells further confirmed the role of ASMase in LPS- and cytokine-induced TF procoagulant activity. Overall, our data indicate that LPS- or cytokine-induced TF procoagulant activity requires the de-encryption of newly synthesized TF protein by ASMase-mediated hydrolysis of SM. The observation that ASMase inhibitors attenuate TF-induced coagulation raises the possibility of their therapeutic use in treating thrombotic disorders associated with aberrant expression of TF.
- Modulation of the neurotransmitter systems through the anti-inflammatory and antidepressant-like effects of squalene from Aurantiochytrium sp. [Journal Article]
- PlosPLoS One 2019; 14(6):e0218923
- Although algae have been the focal point of biofuel research, studies on their biological activities have been limited. In recent years, however, the importance of algae as sources of functional ingr…
Although algae have been the focal point of biofuel research, studies on their biological activities have been limited. In recent years, however, the importance of algae as sources of functional ingredients has been recognized due to their health beneficial effects. In this study, we evaluated the antidepressant-like activities of ethanol extract of Aurantiochytrium sp. (EEA) in the forced swimming test (FST)-induced depression in ICR mice. Imipramine, a commercially available tricyclic antidepressant drug, was used as positive control. Animals were administered EEA orally for 14 consecutive days and were subjected to the locomotor activity testing. Additionally, changes in gene expression in mice brain were assessed by real-time PCR and microarray assays to understand the molecular mechanisms underlying the effect of EEA. We found that the immobility time in FST was significantly reduced in the EEA-treated mice compared to that of in the control mice. Microarray and real-time PCR results revealed that EEA treatment induced changes in several genes in mice brain associated with pro-inflammation and dopaminergic, cholinergic, glutamatergic, and serotonergic synapses. It has previously been reported that several cytokines, such as IL-6 and TNF-α, which mediate neuroinflammation, are also responsible for indirectly altering brain neurotransmitter levels in neuropsychiatric disorders. Therefore, the regulation of the expression of pro-inflammatory genes in EEA-administered mice brain is considered to contribute to the enhancement of neurotransmitter systems-related gene expression in our study. Moreover, our in vitro study suggested that squalene, a component produced by Aurantiochytrium, was one of the active substances in EEA. In conclusion, our study provides the first evidence that Aurantiochytrium sp. can reduce neuroinflammation that may contribute to the modulation of the neurotransmitter systems, which could underlie its antistress and antidepressant effects.
- Esketamine and Rapastinel, but not Imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression. [Journal Article]
- ANActa Neuropsychiatr 2019 Jun 24; :1-23
- CONCLUSIONS: The present data confirms development of a resistance to treatment following chronic ACTH administration. In addition, the study confirms the possible effectiveness of s-ketamine and rapastinel as treatment options in treatment resistant depression. Moreover, it highlights the importance of the glutamatergic system in the neurobiology of depression. Further studies are necessary to evaluate how repeated treatment with ACTH leads to a depressed condition resistant to monoaminergic antidepressants.
- Anxiolytic-Like and Antidepressant-Like Effects of Resveratrol in Streptozotocin-Induced Diabetic Rats. [Journal Article]
- NPNoro Psikiyatr Ars 2019; 56(2):144-149
- CONCLUSIONS: This study indicates that chronic resveratrol treatment may able to treat comorbid anxiety-and depressive-like behaviors in diabetes through inhibition of oxidative stress.
- A novel and sensitive UPLC-MS/MS method to determine mequitazine in rat plasma and urine: Validation and its application to pharmacokinetic studies. [Journal Article]
- BCBiomed Chromatogr 2019 Jun 20; :e4627
- The aim of this study was to develop an analytical method to determine mequitazine in rat plasma and urine. Mequitazine was separated by UPLC-MS/MS equipped with a Kinetex core-shell C18 column (50 ×…
The aim of this study was to develop an analytical method to determine mequitazine in rat plasma and urine. Mequitazine was separated by UPLC-MS/MS equipped with a Kinetex core-shell C18 column (50 × 2.1 mm, 1.7 μm) using 0.1% (v/v) aqueous formic acid and acetonitrile containing 0.1% (v/v) formic acid as a mobile phase by gradient elution at a flow rate of 0.3 mL/min. Quantitation of this analysis was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique operating in multiple reaction monitoring positive ion mode. Mass transitions were m/z 323.3 → 83.1 for mequitazine and 281.3 → 86.3 for imipramine as internal standard. Liquid-liquid extraction with ethyl acetate and protein precipitation with methanol were used for sample extraction. Chromatograms showed that the method had high resolution, sensitivity and selectivity without interference from plasma constituents. Calibration curves for mequitazine in rat plasma and urine were 0.02-200 ng/mL, showing excellent linearity with correlation coefficients (r2) >0.99. Both intra- and inter-day precisions (CV%) were within 4.08% for rat plasma and urine. The accuracies were 99.58-102.03%. The developed analytical method satisfied the criteria of international guidance. It could be successfully applied to pharmacokinetic studies of mequitazine after oral and intravenous administration to rats.
New Search Next
- A single injection of imipramine affected proliferation in the hippocampus of adult Swiss mice depending on the route of administration, doses, survival time and lodging conditions. [Journal Article]
- JCJ Chem Neuroanat 2019 Jun 13; 100:101655
- Swiss mice may be valuable for the screening of antidepressants in preclinical trials. Acute treatment with antidepressants may affect the behaviour of Swiss mice, but the effects on their hippocampa…
Swiss mice may be valuable for the screening of antidepressants in preclinical trials. Acute treatment with antidepressants may affect the behaviour of Swiss mice, but the effects on their hippocampal neurogenesis remain unknown. The present work aims to assess the influence of acute treatment with antidepressants on cell proliferation in the dentate gyrus of the hippocampus of adult Swiss mice. Cell proliferation was estimated by ex vivo counting of Ki-67 immunoreactive nuclei (Ki-67-ir) in the dentate gyrus of Swiss mice housed in standard or enriched environments, at survival-times 2 or 24 h after imipramine injection Independent of the experimental group, intraperitoneal imipramine (0 or 30 mg/kg) failed to change the number of Ki-67-ir in the hippocampus of mice. Through intracerebroventricular route, imipramine reduced the number of Ki-67-ir in the hippocampus of Swiss mice at the dose of 0.06 nmol and increased it at the dose 0.2 nmol. At the dose 0.2 nmol, not 0.06 nmol, imipramine increased the immunoreactivity to doublecortin (a marker for immature neurons) in the hippocampus of mice. The effects of intracerebroventricular injection of imipramine on neurogenesis markers were seen 24 h after the injection in mice housed in standard conditions. The effects of intracerebroventricular injection of imipramine on neurogenesis markers were absent in mice housed in enrichment or 2 h after the injection. These data suggest that acute treatment with imipramine may affect proliferation in the hippocampus of adult Swiss mice depending on the route of administration, doses, survival time and lodging conditions.