共查询到20条相似文献，搜索用时 31 毫秒
1.
Parham Jabbarzadeh Kaboli Melody Pui-Yee Leong Patimah Ismail King-Hwa Ling 《Pharmacological reports : PR》2019,71(1):13-23
Background
Berberine is an alkaloid plant-based DNA intercalator that affects gene regulation, particularly expression of oncogenic and tumor suppressor proteins. The effects of berberine on different signaling proteins remains to be elucidated. The present study aimed to identify the effects of berberine against key oncogenic proteins in breast cancer cells.Methods
Molecular docking and molecular dynamics simulations were used for EGFR, p38, ERK1/2, and AKT. The effects of berberine and lapatinib on MAPK and PI3K pathways in MDA-MB231 and MCF-7 cells were evaluated using immunoflorescence assays, and the amounts of phosphorylated kinases were compared to total kinases after treating with different concentrations of berberine.Results
Simulations showed berberine accurately interacted with EGFR, AKT, P38, and ERK1/2 active sites in silico (scores = -7.57 to -7.92 Kcal/mol) and decreased the levels of active forms of corresponding enzymes in both cell lines; however, berberine binding to p38 showed less stability. Cytotoxicity analysis indicated that MDA-MB231 cells were resistant to berberine compared to MCF-7 cells [72?h IC50?=?50 versus 15 μM, respectively). Also, lapatinib strongly activated AKT but suppressed EGFR in MDA-MB231 cells. The activity of EGFR, AKT, P38, and ERK1/2 were affected by berberine; however, berberine dramatically reduced EGFR and AKT phosphorylation.Conclusion
By way of its multikinase inhibitory effects, berberine might be a useful replacement for lapatinib, an EGFR inhibitor which can cause acquired drug resistance in patients. 相似文献2.
Jagoda Abramek Jacek Bogucki Marta Ziaja-Sołtys Andrzej Stępniewski Anna Bogucka-Kocka 《Pharmacological reports : PR》2019,71(2):248-256
Background
Sodium dichloroacetate (DCA) is an agent with anticancer properties against solid tumors. DCA also seems to have antileukemic activity. In order to affirm it we investigate the effect of DCA on cell viability and apoptotic gene expression profiles in leukemia cell lines: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2.Methods
Cell viability was assessed by trypan blue staining. The expression of 93 genes involved in the process of apoptosis was determined by real-time PCR method using Taqman Low Density Array (TLDA).Results
CEM/C1, CCRF/CEM, HL-60, HL-60/MX2 cells were exposed to DCA for 24?h. The sensitivity of each cell line to DCA is different and depends on the concentration. CEM/C1 was the most sensitive with an half-maximal inhibitory concentration (IC50) value of 30?mM, while HL-60/MX2 was the most resistant with an IC50 value of 75?mM. Exposure of leukemia cells to DCA causes differences in gene expression profiles which cannot indicate that any particular pathway of apoptosis is initiated. However, the presence of 388 statistically significant correlations between expression pattern of gens was determined.Conclusion
We showed that DCA causes a decrease in viability of leukemia cells. The decline depends on DCA concentration. The induction of any particular apoptosis pathway is not shown in cells after DCA treatment. For that reason, studies on the molecular mechanism of cell death after exposure to DCA should be continued. 相似文献3.
Ewa Langner Witold Jeleniewicz Waldemar A. Turski Tomasz Plech 《Pharmacological reports : PR》2019,71(2):189-193
Background
Origin, synthesis and activity of quinaldic acid (QA), proposed derivative of kynurenic acid, have been poorly studied to date. Previously, we have demonstrated the antiproliferative effect of QA in a colon cancer model in vitro. The goal of present study was to verify QA activity to modify the expression of p53 tumor suppressor in colon cancer cells, and to relate it to its cancer cell growth inhibiting activity in vitro.Methods
LS180 colon cancer cells possessing the wild type form of p53 were used in the study. Real-time PCR and immunobloting techniques were used to test the expression of p53 at gene and protein level, respectively. Next, immunocytochemistry was used to visualize the localization of p53 protein within the cells. Furthermore, the antiproliferative activity of QA was retested in cells with siRNA silenced P53 gene.Results
The activity of QA to modify both the expression and phosphorylation of p53 protein as well as the level of P53 gene is shown. Concomitantly, the nuclear and cytoplasmic localization of phospho-p53 protein upon QA treatment is also presented. Moreover, reduced activity of QA in colon cancer cells with silenced p53 expression is observed.Conclusion
QA affects the expression of p53 tumor suppressor, both at gene and protein level. The prominent contribution of p53 to the antiproliferative effect of QA in LS180 colon cancer cells can be suggested. 相似文献4.
Refaat I. ElFayoumi Magda M. Hagras Adel Abozenadaha Mamdouh Gari Ibrahim Abosoudah Thoraia Shinawi Talaat Mirza Waleed Bawazir 《Pharmacological reports : PR》2019,71(1):90-95
Background
Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL.Methods
Three single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs 3213619 T129C, rs 2032582 G2677T and rs1045642 C3435T) were analysed in 70 Saudi children with ALL and 60 control subjects. Participants were treated according to the ALL 2000 study protocol. Toxicities were assessed and associations with genotypes were evaluated according to Common Toxicity Criteria (NCI-CTC).Results
Significant associations were observed among carriers and the mutated genotype C3435T (ABCB1), which had an incidence of infection (p?=?0.05). Although no correlations were found between liver toxicity and glucose abnormalities for patients carrying ABCB1 SNPs, risk factors for liver toxicity were elevated by a factor of three for patients carrying the SNP G2677T, OR 3.00 (1.034–8.702). The risk factor of glucose abnormality toxicity for the patients carring T129C were increased three times OR 3.06 (0.486–19.198).Conclusions
In terms of infection incidence, polymorphism C3435T may contribute to potential life-threatening infections during paediatric ALL therapy, through glucocorticoid usage. 相似文献5.
Mohammed I. Rasool Ahsan F. Bairam Saud A. Gohal Amal A. El Daibani Fatemah A. Alherz Maryam S. Abunnaja Eid S. Alatwi Katsuhisa Kurogi Ming-Cheh Liu 《Pharmacological reports : PR》2019,71(2):257-265
Background
Non-opioid and opioid analgesics, as over-the-counter or prescribed medications, are widely used for the management of a diverse array of pathophysiological conditions. Previous studies have demonstrated the involvement of human cytosolic sulfotransferase (SULT) SULT1A1 in the sulfation of acetaminophen, O-desmethylnaproxen (O-DMN), and tapentadol. The current study was designed to investigate the impact of single nucleotide polymorphisms (SNPs) of the human SULT1A1 gene on the sulfation of these analgesic compounds by SULT1A1 allozymes.Methods
Human SULT1A1 genotypes were identified by database search. cDNAs corresponding to nine SULT1A1 nonsynonymous missense coding SNPs (cSNPs) were generated by site-directed mutagenesis. Recombinant wild-type and SULT1A1 allozymes were bacterially expressed and affinity-purified. Purified SULT1A1 allozymes were analyzed for sulfation activity using an established assay procedure.Results
Compared with the wild-type enzyme, SULT1A1 allozymes were shown to display differential sulfating activities toward three analgesic compounds, acetaminophen, O-desmethylnaproxen (O-DMN), and tapentadol, as well as the prototype substrate 4NP.Conclusion
Results obtained indicated clearly the impact of genetic polymorphisms on the drug-sulfation activity of SULT1A1 allozymes. Such information may contribute to a better understanding about the differential metabolism of acetaminophen, O-DMN, and tapentadol in individuals with different SULT1A1 genotypes. 相似文献6.
Fatemeh Delrobaei Iman Fatemi Ali Shamsizadeh Mohammad Allahtavakoli 《Pharmacological reports : PR》2019,71(1):133-138
Background
Menopause is associated with increased oxidative stress and memory impairment. Based on the antioxidant property of ascorbic acid (AA), It’s effect on cognitive function, the serum level of the brain-derived neurotrophic factor (BDNF) and the activity of antioxidant enzymes within the brain in ovariectomized (OVX) mice was investigated.Methods
AA (100, 300 and 500?mg/kg), was orally administrated per day in OVX mice for 30 days. Tactile learning and working memory were evaluated by the novel object recognition task and T-maze continuous alternation task, respectively. The levels of serum BDNF were measured and animals’ brains were analyzed for the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity.Results
AA prevented from the deleterious effects of ovariectomy on learning memory (300 and 500?mg/kg) and working memory (100 and 500?mg/kg). The serum BDNF level was also increased in OVX animals treated with AA (100 and 500?mg/kg). Furthermore, AA (500?mg/kg) increased the SOD and GPx activity in the brain of OVX animals.Conclusions
Collectively, the results of the present study suggest that AA might be an appropriate choice in loss or reduction of estradiol for the amelioration of cognitive impairment. 相似文献7.
Jan Detka Joanna Ślusarczyk Anna Kurek Mateusz Kucharczyk Tomasz Adamus Paweł Konieczny Marta Kubera Agnieszka Basta-Kaim Władysław Lasoń Bogusława Budziszewska 《Pharmacological reports : PR》2019,71(2):338-346
Background
In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.Methods
Adult male PS rats were subjected to acute stress and/or received orally glucose. Levels of hormones and their receptors were assayed with ELISA method. In vitro studies were performed on mHypoA-2/12?hypothalamic cell line, stably transfected with CRH promoter coupled with luciferase.Results
PS has reduced GLP-1 and GLP-1R levels, attenuated glucose-induced increase in insulin concentration and increased the amount of phosphorylated IR in the hypothalamus of animals subjected to additional stress stimuli, and also decreased the GLP-1R level in the hippocampus. In vitro studies demonstrated that insulin is capable of increasing CRH promoter activity in the condition of stimulation of the cAMP/PKA pathway in the applied cellular model.Conclusion
Prenatal stress may act as a preconditioning factor, affecting the concentrations of hormones such as insulin and GLP-1 in the hypothalamus in response to adverse stimuli. The decreased GLP-1R level in the hippocampus could be linked with the disturbances in neuronal plasticity. 相似文献8.
Aleksandra Sałagacka-Kubiak Marta Żebrowska-Nawrocka Agnieszka Jeleń Marek Mirowski Ewa Balcerczak 《Pharmacological reports : PR》2019,71(2):272-275
Background
CYP2C19 isoenzyme of cytochrome P450 in the liver catabolises proton pump inhibitors, one of the therapeutics utilized in Helicobacter pylori eradication therapy, and in this way could influence the eradication effectiveness. The isoensyme contributes also to metabolism of endogenous substances, which derivatives are involved in the pathogenesis of peptic ulceration. CYP2C19*2 polymorphism (rs4244285) changing the CYP2C19 function could be relevant in the predisposition to peptic ulcer disease.Methods
CYP2C19*2 polymorphism in 197 peptic ulcer patients and 107 healthy subjects of Polish origin by PCR-RFLP method was investigated.Results
There were no statistically significant differences in genotypes and alleles frequencies for investigated polymorphism between peptic ulcer patients and healthy individuals. No associations between frequencies of particular CYP2C19 genotypes and alleles and the presence of H. pylori infection in peptic ulcer patients were stated. However, significant association between CYP2C19*2 and gender in H. pylori-infected but not -uninfected peptic ulcer individuals was found.Conclusions
Investigated polymorphism is not a risk factor for peptic ulcer in Polish population. Obtained results could suggested there is some interaction between gender, CYP2C19*2 polymorphism, and pathogenesis of H. pylori infection development. However, this hypothesis should be verified in the further studies. 相似文献9.
Background
Both selenium and vitamin D were found to reduce thyroid antibody titers in women with Hashimoto’s thyroiditis.Methods
The study enrolled 37 young drug-naïve euthyroid men with autoimmune thyroiditis, who were treated for 6 months with either exogenous vitamin D (group A, n?=?20) or selenomethionine (group B, n?=?17). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin and free thyroid hormones, serum levels of 25-hydroxyvitamin D, as well Jostel’s thyrotropin, the SPINA-GT and the SPINA-GD indices were determined at the beginning and at the end of the study.Results
At baseline, there were no differences between the study groups. Both vitamin D and selenomethionine reduced antibody titers and increased the SPINA-GT index. Only selenomethionine affected the SPINA-GD index, while only vitamin D increased 25-hydroxyvitamin D levels. Neither selenomethionine nor vitamin D significantly affected thyrotropin and free thyroid hormone levels. The effect of vitamin D on antibody titers correlated with baseline and treatment-induced changes in serum levels of 25-hydroxivitamin D.Conclusions
Both vitamin D and selenomethionine have a beneficial effect on thyroid autoimmunity in drug-naïve men with Hashimoto’s thyroiditis. 相似文献10.
Reza Fartootzadeh Fatemeh Azizi Hojjatallah Alaei Parham Reisi 《Pharmacological reports : PR》2019,71(2):361-366
Background
The nucleus accumbens core (NAcc) expresses both orexin and nicotinic acetylcholine receptors (nAChRs). Orexin is among important neurotransmitters, which regulates addictive properties of drugs of abuse including nicotine. The role of orexin-2 receptor (OX2R) in the regulation of NAcc neural activity in response to nicotine has not yet been studied. Hence, in this study, we examined whether the OX2R antagonist (TCS-OX2-29) can adjust the effects of nicotine on electrical activity of NAcc neurons, in urethane-anesthetized rats, using the single unit recording.Methods
Neuronal firing of NAcc was recorded for 15?min, then TCS-OX2-29 (OX2R-antagonist; 1, 3 and 10?ng/rat) or DMSO were microinjected into NAcc, just 5?min before subcutaneous (sc) administration of nicotine (0.5?mg/kg) or saline. The spontaneous firing activity was recorded for 70?min, after nicotine injection.Results
The results demonstrated that nicotine significantly excites the NAcc neurons and interestingly, the administration of TCS-OX2-29 (3 and 10?ng/rat) into the NAcc, inhibited nicotine-induced increases of NAcc neuronal responses. Furthermore, administration of TCS-OX2-29 (10?ng/rat), just 5?min before sc administration of saline instead of nicotine, did not significantly alter the neuronal responses, compared to the saline-control group.Conclusion
Our results showed that, although OX2R blockade alone did not affect neuronal activity in the NAcc, it was able to prevent the exciting effects of nicotine on NAcc neuronal activity. Therefore, we proposed that orexin has a potential modulator effect, in response to nicotine. 相似文献11.
Yueh-Lun Lee Ling-Heng Hsu Yueh-Hsiung Kuo Chen-Chen Lee 《Pharmacological reports : PR》2019,71(2):194-200
Background
Caffeic amides are derivatives of caffeic acid, which have antioxidant and anti-inflammatory properties, and high in vivo stability. The therapeutic effect of caffeic amides on allergic diseases, and especially on the maturation of bone marrow-derived dendritic cells (BM-DCs), remains unclear. In this study, we investigated the therapeutic potential of caffeic amides on allergic diseases by evaluating the maturation of DCs and evaluated their potential in inducing the differentiation of TH2 cells.Methods
BM-DCs isolated from BALB/c mice were treated with different caffeic amide derivatives for 48?h and the expression of surface markers was analyzed by flow cytometry. The differentiation of CD4+ T cells was detected by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay and cytokine production was analyzed by ELISA.Results
Our results showed that among the six caffeic amides tested herein, only 36?M significantly inhibited the antigen-induced maturation of DCs associated with the expression of CD80, CD86, and major histocompatibility complex II (VC ovalbumin (OVA)+ thymic stromal lymphopoietin (TSLP) vs. 36?M OVA?+?TSLP). Additionally, the isolation and co-culture of antigen-specific CD4+ T cells with 36?M-treated BM-DCs suppressed the antigen-specific differentiation of TH2 cells.Conclusion
Among the six caffeic amides tested herein, 36?M (N-octyl caffeamide) might possess therapeutic potential for allergic diseases. 相似文献12.
Yosuke Suzuki Nanako Muraya Takashi Fujioka Fuminori Sato Ryota Tanaka Kunihiro Matsumoto Yuhki Sato Keiko Ohno Hiromitsu Mimata Satoshi Kishino Hiroki Itoh 《Pharmacological reports : PR》2019,71(2):276-281
Background
Phenoconversion is a phenomenon whereby some genotypic extensive metabolizers transiently exhibit drug metabolizing enzyme activity at similar level as that of poor metabolizers. Renal failure is known to decrease CYP3A activity in humans. Indoxyl sulfate, parathyroid hormone (PTH), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) have been reported to cause CYP3A downregulation in renal failure. We measured plasma concentrations of the above compounds in stable kidney transplant recipients, and evaluated their relations with phenoconversion of CYP3A evaluated by plasma concentration of 4β-hydroxycholesterol, a biomarker of CYP3A activity. Phenoconversion was defined as a genotypic extensive/intermediate metabolizer exhibiting CYP3A activity below the cutoff value that discriminates extensive/intermediate from poor metabolizers.Methods
Sixty-three Japanese kidney transplant recipients who underwent transplantation more than 180 days prior to the study were included. Morning blood samples were collected, and CYP3A5 polymorphism as well as plasma concentrations of 4β-hydroxycholesterol, indoxyl sulfate, intact-PTH, IL-6 and TNF-α were determined.Results
Significantly higher plasma 4β-hydroxycholesterol concentration was observed in recipients with CYP3A5*1 allele (n?=?23) compared to those without the allele (n?=?40), and the cut-off value was 40.0?ng/mL. Ten recipients with CYP3A5*1 allele exhibited CYP3A activity below 40.0?ng/mL (phenoconversion). Only plasma indoxyl sulfate concentration was significantly higher in recipients with CYP3A phenoconversion compared to those without phenoconversion.Conclusions
These findings suggest that higher plasma indoxyl sulfate concentration may be involved in CYP3A phenoconversion. Dose adjustment of drugs metabolized by CYP3A may be needed in patients with CYP3A5*1 allele and high blood indoxyl sulfate. 相似文献13.
Hubert Zatorski Maciej Salaga Marta Zielińska Andrzej Wasilewski Aleksandra Misicka Mariusz Sacharczuk Jakub Fichna 《Pharmacological reports : PR》2019,71(2):218-224
Background
Gastric mucosal injury appears when acid and pepsin production, simultaneously with inadequate mucosal response, overwhelms protective mechanism in stomach. Here we aimed to explore the linkage between gastric lesion formation and endogenous opioid system activity.Methods
Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low endogenous opioid system activity were used. Gastric mucosal injury was induced by ethanol (EtOH) and chronic mild stress. To investigate the anti-inflammatory effect of the endogenous opioid system macroscopic score, myeloperoxidase (MPO) activity, the expression of inflammatory molecules as well as oxidative stress markers were determined. Moreover, expression of opioid receptors μ (MOR), κ (KOR) and δ (DOR) at mRNA levels were determined in gastric tissue.Results
High activity of the endogenous opioid system alleviated gastric lesions development in the EtOH-and chronic mild stress-induced mouse gastric mucosal injury models, as demonstrated by decreased macroscopic score in HA line compared to LA. Additionally, antioxidative stress defence mechanisms were positively modulated in both models of gastric mucosal injury. MOR and partially KOR receptors may be responsible for the gastroprotective effect.Conclusion
To our knowledge this is the first study to show that increased activity of the endogenous opioid system prevents from gastric lesion formation by influencing – among others – the anti-inflammatory and anti-oxidant mechanisms in the mice stomach. Hence, we suggest that opioids may play an important role in gastric mucosal injury prevention. 相似文献14.
Insights into the structure and tubulin-targeted anticancer potential of N-(3-bromobenzyl) noscapine
Sanith Cheriyamundath Tejashree Mahaddalkar Praveen Kumar Reddy Nagireddy Balasubramanian Sridhar Srinivas Kantevari Manu Lopus 《Pharmacological reports : PR》2019,71(1):48-53
Background
Noscapine is a non-narcotic, antitussive alkaloid isolated from plants of Papaveraceae family. This benzylisoquinoline alkaloid and its synthetic derivatives, called noscapinoids, are being evaluated for their anticancer potential.Methods
The structure of a novel analogue, N-(3-bromobenzyl) noscapine (N-BBN) was elucidated by X-ray crystallography. Effect of N-BBN on cancer cell proliferation and cellular microtubules were studied by sulphorhodamine B assay and immunofluorescence, respectively. Binding interactions of the alkaloid with tubulin was studied using spectrofluorimetry.Results
N-BBN, synthesized by introducing modification at site B (‘N’ in isoquinoline unit) and a bromo group at the 9th position of the parent compound noscapine, was found to be superior to many of the past-generation noscapinoids in inhibiting cancer cell viability and it showed a strong inhibition of the clonogenic potential of an aggressively metastatic breast tumour cell line, MDA-MB-231. The compound perturbed the tertiary structure of purified tubulin as indicated by an anilinonaphthalene sulfonic acid-binding assay. However, substantiating the common feature of noscapinoids, it did not alter microtubule polymer mass considerably. In cells, the drug-treatment showed a peculiar type of disruption of normal microtubule architecture.Conclusion
N-BBN may be considered for further investigations as a potent antiproliferative agent. 相似文献15.
Gabriela Handzlik Michał Holecki Joanna Kozaczka Michał Kukla Katarzyna Wyskida Leszek Kędzierski Krzysztof Pawlicki Jan Duława 《Pharmacological reports : PR》2019,71(2):183-188
Background
Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of liver disease worldwide. There is growing evidence on pathogenesis and pathophysiology of NAFLD. However, there is still no universally accepted pharmacotherapy protocol.Methods
The study was conducted on 42 patients with NAFLD. They were randomized to dietary treatment alone (n?=?21) or to diet and metformin therapy (n?=?21). Liver ultrasonography, controlled attenuation parameter (CAP), liver stiffness (LS), complete blood count, anthropometric and biochemical parameters were obtained before treatment (baseline), and after 3 and 5 months of the therapy.Results
Patients treated with diet and metformin exhibited significantly decreased CAP values at 3 and 5 months of the therapy compared to baseline (319?dB/m vs. 285?dB/m; p < 0.05; 319?dB/m vs. 295?dB/m; p < 0.05 respectively). Five months of diet and the metformin therapy resulted in significant reduction of LS value (6.2?kPa vs. 5.2?kPa; p?<? 0.05), while patients treated with diet alone had no significant changes in liver CAP and LS measurements.Conclusions
Metformin therapy combined with dietary treatment seems to be effective for the reduction of hepatic steatosis and fibrosis. However, considering limitations of the study and inconsistent results of previous investigations in this area, there is a need for further research on metformin efficacy in this group of patients. 相似文献16.
Background
The osmolyte and antioxidant taurine plays an important role in regulation of cellular volume, oxidative status and Ca2+-homeostasis. Taurine uptake in human cells is regulated by the Na+- and Cl?-dependent taurine transporter TauT. In order to gain deeper structural insights about the substrate binding pocket of TauT, a HEK293 cell line producing a GFP-TauT fusion protein was generated.Methods
Transport activity was validated using cell-based [3H]-taurine transport assays. We determined the Km and IC50 values of taurine, β-alanine and γ-aminobutyrate. Additionally we were able to identify structurally similar compounds as potential new substrates or inhibitors of the TauT transporter. Substrate induced cytotoxicity was analyzed using a cell viability assay.Results
In this study we show competitive effects of the 3-pyridinesulfonate, 2-aminoethylhydrogen sulfate, 5-aminovalerate, β-aminobutyrate, piperidine-4-sulfonate, 2-aminoethylphosphate and homotaurine. We demonstrate that taurine uptake can be inhibited by a phosphate. Furthermore our studies revealed that piperidine-4-sulfonate interacts with TauT with a higher affinity than γ-aminobutyrate and imidazole-4-acetate.Conclusion
We propose that piperidine-4-sulfonate may serve as a potential lead structure for the design of novel drug candidates required for specific modulation of the TauT transporter in therapy of neurodegenerative diseases. 相似文献17.
Duygun Altıntaş Aykan Tuba Tulay Koca Selma Yaman Nadire Eser 《Pharmacological reports : PR》2019,71(2):306-310
Background
We hypothesized that renin-angiotensin system and neprilysin (NEP) inhibition can modulate the nociceptive parameters on hypertensive rats. The aim of this study is to assess the preventive and therapeutic effects of ramipril and sacubitril on the pain hypersensitivities, and their interaction mechanisms with high blood pressure.Methods
Antinociceptive effects of ramipril and sacubitril were compared with those of diclofenac. Threshold of pain assesments were recorded before drugs administration. After a 18 days treatment, normotensive and dexamethasone-induced hypertensive rats were evaluated on thermal hyperalgesia and mechanical allodynia tests. Blood pressure of rats were verified by mean arterial pressure measurement.Results
Hypertensive rats showed significantly high pain threshold on thermal plantar test compared to that of normotensives. Among hypertensive rats, pain hypersensitivity was lowest in diclofenac group, followed by sacubitril group, while ramipril caused increased thermal and mechanical hypersensitivities.Conclusion
We found that NEP inhibition may play a role in nociception in hypertensive rats. NEP inhibitors may be suitable choice for the management of hypertension and pain because of their therapeutic and preventive effects on nociception and arterial blood pressure. 相似文献18.
Marek Zadrozniak Marcin Szymanski Jarogniew J. Luszczki 《Pharmacological reports : PR》2019,71(2):351-356
Background
Drug-induced ototoxicity is still a main clinical problem in otolaryngology. It is widely known that aminoglycoside antibiotics combined with loop diuretics significantly contribute to permanent ototoxicity. The aim of this study was to find out whether ascorbic acid (vitamin C) is able to reverse or alleviate ototoxicity evoked by systemic (ip) administration of combination of amikacin and furosemide in experimental male albino Swiss mice.Methods
Ototoxic combination of amikacin and furosemide was isobolographically evaluated based on the hearing threshold decreasing doses by 20% and 50% (TDD20 and TDD50), respectively. Linear regression analysis was used to determine the TDD20 and TDD50 values for amikacin, furosemide, vitamin C administered alone and in combination (at the fixed-ratio of 1:1).Results
Vitamin C (in a dose of 500?mg/kg, ip) alleviated the impairment in hearing threshold evoked by combined ip administration of amikacin and furosemide (at the fixed-ratio of 1:1) in mice by reducing TDD50 values from 49.82 to 21.56 (p?<? 0.01). In contrast, vitamin C (500?mg/kg, ip) had no significant effect on TDD20 values for the combination of amikacin and furosemide at the fixed-ratio of 1:1.Conclusions
Vitamin C administered together with ototoxic drug combination of amikacin and furosemide reduced ototoxicity evoked by this two-drug combination in the experimental mice. 相似文献19.