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1.
Background
Limited data demonstrate the effect of nickel released from orthodontic appliances. The mechanism of this action is not clear. The present study aimed to investigate the role of kynurenines, oxidative stress and caspase pathway in the mechanism of nickel action.Methods
We studied the concentration of nickel, 3-hydroxykynurenine, total oxidative status in saliva and caspase-3 in epithelial cells in 10 subjects before and one week after orthodontic treatment.Results
Orthodontic appliances significantly enhanced the concentration of nickel, 3-hydroxykynurenine, total oxidative status and augmented the expression of caspase-3 seven days after treatment in the oral cavity in respect to pre-treatment values.Conclusion
Our data suggest that nickel released from orthodontic appliances activate tryptophan metabolism in oral cavity via the kynurenine pathway. The metal directly or through kynurenines enhancement activates oxidative stress and then via the caspase pathway induce apoptosis of buccal epithelial cells. 相似文献2.
Jinyan Han Ping Zhao Weiqin Shao Zengmin Wang Fengxue Wang Lei Sheng 《Pharmacological reports : PR》2018,70(5):853-862
Background
Acute lymphoblastic leukemia (ALL) is the most common fatal cancer in people younger than 20 years of age. This study was designed to explore the anti-leukemia activity of physcion 8-O-β-glucopyranoside (PG) in B-cell ALL.Methods
NALM6 and SupB15 cells were used as model cell lines. Cell viability, cell apoptosis, cell cycle distribution were determined by CCK-8 assay, DNA fragmentation assay and flow cytometry, and flow cytometry, respectively. Expression of proteins involved in cell apoptosis and cell cycle regulation was determined by western blot and the levels of ceramide and sphingosine 1-phosphate (S1P) were determined by ELISA. Activity of sphingosine kinase 1 (SphK1) was also determined with a Sphingosine Kinase Assay Kit. In the present study, both model cell lines were transfected with siRNA targeting SphK1 or an overexpression plasmid to examine the role of SphK1 in the anti-leukemia activity of PG. Moreover, the efficacy of PG was examined in vivo in a mouse model by measuring survival and spleen weight.Results
Our results provided experimental evidence that PG could significantly induce apoptosis and cell cycle arrest in vitro. Mechanistically, the anti-leukemia activity of PG was mediated by its ability to repress SphK1 and thus modulate ceramide-S1P rheostat. Moreover, the anti-leukemia activity of PG was also verified in a murine model.Conclusion
Collectively, our results indicate that PG may be a promising agent for the treatment of B-cell leukemia. 相似文献3.
Background
Long term use of glucocorticoids is one of the most common causes of secondary osteoporosis. Osteocyte, the most abundant cell type in bone, coordinates the function of osteoblast and osteoclast. This study evaluates the protective effect of alpinumisoflavone (AIF), a naturally occurring flavonoid compound, on dexamethasone (Dex)-induced apoptosis of osteocytes.Methods
MLO-Y4 cell was used as a cell model. The effect of AIF on the cell viability was assessed by MTT assay. Apoptosis of MYL-Y4 cells was determined by DNA fragment detection ELISA kit and flow cytometry. Intracellular ROS level was determined by DCFH-DA staining. mRNA and protein expression of target genes were determined by qRT-PCR and western blot, respectively.Results
AIF effectively protected MLO-Y4 cells against Dex-induced apoptosis, which was associated with attenuation of Dex-induced ROS generation in MLO-Y4 cells. Furthermore, our data indicated that the expression of NAD(P)H oxidase 2 (Nox2) was suppressed by AIF, which in turn mediated the attenuating effect on Dex-induced ROS generation and apoptosis in MLO-Y4 cells. Moreover, our results showed that AIF modulated the expression of Nox2 by activating AMPK signaling.Conclusion
AIF activated AMPK-dependent Nox2 signaling pathway to suppress Dex-induced ROS production in cultured osteocytes, which might explain its anti-apoptotic effect. These results indicate that activation of AMPK pathway by AIF could have beneficial effects on bone damage induced by excessive oxidative stress and osteocyte apoptosis. 相似文献4.
Artur Beberok Dorota Wrześniok Aldona Minecka Jakub Rok Marcin Delijewski Zuzanna Rzepka Michalina Respondek Ewa Buszman 《Pharmacological reports : PR》2018,70(1):6-13
Background
Low effectiveness of anti-melanoma therapies makes it necessary to search for new drugs that could improve or replace the standard chemotherapy. Fluoroquinolones are a group of synthetic antibiotics, used in the treatment of wide range of bacterial infections. Moreover, this class of antibiotics has shown promising anti-tumor activity in several cancer cell lines. The aim of this study was to examine the effect of ciprofloxacin on cell viability, apoptosis and cell cycle distribution in COLO829 melanoma cells.Methods
Cell viability was evaluated by the WST-1 assay. Cell cycle distribution and apoptosis in cells exposed to ciprofloxacin was analyzed by the use of fluorescence image cytometer NucleoCounter NC-3000.Results
Ciprofloxacin decreased the cell viability in a dose- and time-dependent manner. For COLO829 cells treated with ciprofloxacin for 24?h, 48?h and 72?h the values of IC50 were found to be 0.74?mM, 0.17?mM and 0.10?mM, respectively. The oligonucleosomal DNA fragmentation was observed when the cells were exposed to ciprofloxacin in concentration of 1.0?mM for 48?h and 72?h. At lower ciprofloxacin concentrations (0.01?mM and 0.1?mM) cells were arrested in S-phase suggesting a mechanism related to topoisomerase II inhibition. Moreover, it was demonstrated that ciprofloxacin induced apoptosis as a result of mitochondrial membrane breakdown.Conclusions
The obtained results for COLO829 melanoma cells were compared with data for normal dark pigmented melanocytes and the use of ciprofloxacin as a potential anticancer drug for the treatment of melanoma in vivo was considered. 相似文献5.
Background
Nitidine chloride (NC) is known to exert anticancer and anti-metastatic effects on a variety of tumors. Recently, NC has also been shown to inhibit PIK3/AKT/mTOR axis in U87 human glioma cells.Methods
The study shows NC employing pDok2, caspase 3 dependent cell death in C6 rat glioma and U87 human malignant glioblastoma cells. The effect of NC on glioblastoma cell lines was accessed by MTT, clonogenic and wound healing assays. Cell cycle analysis was performed by FACS. Moreover, the effect of NC on downstream target proteins, such as caspase3, pDok2, PARP, and Gsk3 beta, were measured by western blotting.Results
Overexpressed pDok2 protein has recently been reported as a prognostic marker with poor outcomes for human glioblastoma multiformae. We found that NC inhibits pDok2 in U87 cells in a concentration-dependent way. We further showed that cleaved PARP and cleaved caspase 3 protein expressions were increased in C6 cells treated with NC in a dose-dependent way. NC effectively attenuated C6 cells growth and colony formation at 8 μM (micromoles) concentration. Cell cycle arrest in G2/M phase was further confirmed by flow cytometry. NC also exhibited its inhibitory effect on Gsk3 beta, which has been proven to be altered in glioma biology.Conclusions
Collectively, we predicted that NC could be employed as a potential anti-glioma mediator that needs attention to explore the mechanisms of its activity. 相似文献6.
Isabella dos Santos Guimarães Taciane Ladislau-Magescky Nayara Gusmão Tessarollo Diandra Zipinotti dos Santos Etel Rodrigues Pereira Gimba Cinthya Sternberg Ian Victor Silva Leticia Batista Azevedo Rangel 《Pharmacological reports : PR》2018,70(3):409-417
Background
Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy. Primary cytoreductive surgery with adjuvant taxane-platinum chemotherapy is the standard treatment to fight ovarian cancer, however, their side effects are severe, and chemoresistance emerges at high rates. Therefore, EOC clinic urges for novel treatment strategies to reverse chemoresistance and to improve the survival rates. Metformin has been shown to act in synergy with certain anti-cancer agents, overcoming chemoresistance in various types of tumors. This paper aims to investigate the use of metformin as a new treatment option for cisplatin- and paclitaxel-resistant ovarian cancer.Methods
The effects of metformin alone or in combination with conventional drugs on resistant EOC cell lines were investigated using the MTT assay for cell proliferation; Flow Cytometry analysis for cell cycle and the mRNA expression was analyzed using the real-time PCR technique.Results
We found that metformin exhibited antiproliferative effects in paclitaxel-resistant A2780-PR, and in cisplatin-resistant ACRP cell lines. The combined therapy containing conventional drugs and metformin improved the effect of the treatment in cell proliferation rate, especially in the resistant cells. We found that metformin, in clinical relevant doses, could significantly reduce the mRNA expression of inflammatory cytokines and NF-κB signaling pathway.Conclusions
Taken together, our observations suggest that metformin inhibits the inflammatory pathway induced by paclitaxel and cisplatin treatment. Furthermore, metformin in combination with paclitaxel or cisplatin improved the sensitivity in drug-resistant ovarian cancer cells. Therefore, metformin may be beneficial treatment strategy, particularly in patients with tumors refractory to platinum and taxanes. 相似文献7.
Yoshihiro Nakatsu Fumio Nakagawa Sen Higashi Tomoko Ohsumi Shunji Shiiba Seiji Watanabe Hiroshi Takeuchi 《Pharmacological reports : PR》2018,70(1):29-36
Background
N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear. Therefore, we investigated the effect of APAP on osteoblastic differentiation and cell migration, with a particular focus on TRP channels and CB1.Methods
Effects of APAP on osteoblastic differentiation and cell migration of MC3T3-E1, a mouse pre-osteoblast cell line, were assessed by the increase in alkaline phosphatase (ALP) activity, and both wound-healing and transwell-migration assays, respectively.Results
APAP dose-dependently inhibited osteoblastic differentiation, which was well correlated with the effects on COX activity compared with other NSAIDs. In contrast, cell migration was promoted by APAP, and this effect was not correlated with COX inhibition. None of the agonists or antagonists of TRP channels and the CB receptor affected the APAP-induced cell migration, while the effect of APAP on cell migration was abolished by down-regulating TRPV4 gene expression.Conclusion
APAP inhibited osteoblastic differentiation via COX inactivation while it promoted cell migration independently of previously known targets such as COX, TRPV1, TRPA1 channels, and CB receptors, but through the mechanism involving TRPV4. APAP may have still unidentified molecular targets that modify cellular functions. 相似文献8.
Maria João Rodrigues Catarina Vizetto-Duarte Katkam N. Gangadhar Gokhan Zengin Adriano Mollica João Varela Luísa Barreira Luísa Custódio 《Pharmacological reports : PR》2018,70(5):896-899
Background
Juncunol is a phenanthrene isolated from the halophyte species Juncus acutus, with selective cytotoxic activity towards human hepatocarcinoma (HepG2) cells. However, its mechanism of action is unknown.Methods
The in vitro cytotoxic mechanism of juncunol was evaluated on HepG2 cells through several methods to elucidate its potential to induce apoptotic features, decrease mitochondrial membrane potential, promote internal ROS production and influence cell cycle. We also report its haemolytic activity on human erythrocytes and in silico DNA-binding studies.Results
Juncunol induced an increase in the number of apoptotic cells in a concentration-dependent manner, accompanied by a decrease in the mitochondrial membrane potential. No significant differences were observed in production of reactive oxygen species (ROS). Moreover, juncunol application at the IC50 value significantly induced cell cycle arrest in the G0/G1 phase comparatively to the control group. No significant haemolysis was detected. In silico studies indicate that juncunol seems to bind between GC base pairs.Conclusion
Juncunol reduced HepG2 cells proliferation through the induction of apoptotic cellular death, in a concentration-dependent manner. Apoptosis induction seems to be related with a decrease of the mitochondrial membrane potential but not with ROS production. Juncunol had no haemolytic activity and may act as a DNA intercalator. Our data suggests juncunol as a suitable candidate for more detailed studies, including in vivo experiments, in order to completely characterize its mode of action. 相似文献9.
Zekrayat J.H. Medras Norhan M. El-Sayed Sawsan A. Zaitone Eman A. Toraih Manal M. Sami Yasser M. Moustafa 《Pharmacological reports : PR》2018,70(2):233-242
Background
Glutamine aminoacid regulates insulin exocytosis from pancreatic β-cells. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has fascinated function in inhibiting β-cell apoptosis and preserving pancreatic β-cell mass. The present study investigated the benefit of adding glutamine to a regimen of liraglutide in diabetic rats focusing on their role in increasing insulin production and upregulation of the expression of sodium-dependent neutral aminoacid transporter-2 (SNAT2).Methods
In the present study, diabetes mellitus was induced in rats using streptozotocin (STZ, 50 mg/kg, ip). Male rats were allocated into 5 groups, (i) vehicle group, (ii) STZ-diabetic rats, (iii) STZ-diabetic rats treated with liraglutide (150 μg/kg, sc), (iv) STZ-diabetic rats treated with glutamine (po) and (v) STZ-diabetic rats treated with a combination of liraglutide and glutamine for four weeks. After finishing the therapeutic courses, the fasting blood glucose value was determined and rats were sacrificed. Pancreases were used for quantification of mRNA expression for SNAT2. Paraffin fixed samples were used for histologic staining and immunohistochemistry for insulin and apoptosis markers (activated caspase-3, BCL2 and BAX).Results
Treatment with liraglutide and/or glutamine enhanced insulin production and hence glycemic control in diabetic male rats with favorable effects on apoptosis markers. Treatment with glutamine and its combination with liraglutide significantly increased pancreatic expression of SNAT2 by approximately 30–35 folds.Conclusion
Addition of glutamine to liraglutide regimen enhances the glycemic control and may have utility in clinical settings. 相似文献10.
Background
The association between p53 protein phosphorylated at serine 15 (Ser15), serine 20 (Ser20) and ovarian tumor cell sensitivity after chemotherapy was analyzed in order to define the influence of p53 activation on tumor cell sensitivity to chemotherapy.Methods
The study was performed on ovarian cancer cell line (OvBH-1), colon adenocarcinoma metastasis to ovary (SW626) and on cells isolated from ascitic fluids from patients with ovarian cancer: with (p53+) or without (p53?) p53 nuclear protein accumulation. p53 protein, Ser15, Ser20, Bax, Noxa and PgP protein expression was evaluated by means of immunocytochemical staining before and after chemotherapy. Cell viability after treatment was estimated using MTT assay.Results
Cell lines and tumor cells p53+, p53- revealed a significant decrease in cell survival after camptothecin, paclitaxel, cisplatin treatment, compared to the control group (p?<?0.01). In p53+ group, the expression of Ser20 significantly increased after camptothecin and paclitaxel (p?<?0.05). Ser15, Ser20, Bax, Noxa expression correlated with MTT and depended on p53+, p53? tumor cell and the drug used (p?<?0.05). Expression of Bax and Noxa were dependent on the type of tumor cells and drug used. The correlation between Ser15, Ser20 and Bax, Noxa expression was found in cell lines and tumor cells (p?<?0.05).Conclusions
Our study suggests that the relation between Ser15 or Ser20 and tumor cell viability might reflect their role in tumor sensitivity on chemotherapy in dependent p53 protein status. Revealed association between p53 protein phosphorylated at Ser15, Ser20 and Bax, Noxa protein expression determined the apoptotic activity of tumor cells. 相似文献11.
Abdulkadir Tasdemir Mehmet Taskiran Nusret Ayyildiz 《Pharmacological reports : PR》2018,70(5):885-889
Background
The most common headache associated with epilepsy occurs after seizure activity and is called a postictal headache. Therefore, the objective of this study was to investigate the effects of low and high doses acetylsalicylic acid (aspirin) on a penicillin-induced experimental epilepsy model.Methods
Adult male Wistar rats (n?=?28, weighing 220?±?40?g) were used in the experiments. The rats were divided into four groups as Control, Penicillin, Aspirin 150?mg/kg, Aspirin 500?mg/kg. Seizure activity was triggered by an intracortical injection of penicillin G potassium (500?IU/2.5?μl) into the sensory motor cortex. An electrocorticogram was recorded by using conductive screw electrodes. Aspirin at the doses of 500?mg/kg and 150?mg/kg was given intraperitoneally (ip) 30?min after penicillin administration.Results
Anticonvulsant activity appeared at the 30th and 40th min after an intracortically administered injection of penicillin in the groups given aspirin doses of 500?mg/kg (ip) and 150?mg/kg (ip) respectively. The amplitude of epileptiform activity at both doses of aspirin decreased but the difference was not statistically significant.Conclusions
The results of the present study suggest that low and high doses of aspirin may decrease epileptiform activity in penicillin-induced epilepsy. Aspirin might be suggested for headache associated with epilepsy. 相似文献12.
Anita K. Bakrania Bhavesh C. Variya Snehal S. Patel 《Pharmacological reports : PR》2018,70(3):549-557
Background
Angiogenesis, the physiological process involving growth of new blood vessels from preexisting vessels, is essential for organ growth and repair. However, the imbalance in angiogenesis contributes to copious pathologies including cancer. Preceding the development of anti-angiogenic or proangiogenic agents, its evaluation is equally imperative; hence, precise and adequate models required. Valid mammalian models are expensive, time-consuming and not easy to set up, instigating legal and ethical aspects making it necessary to establish models with satisfactory activity and limited drawbacks.Methods
We investigated the activity of DEAE-Dextran on diversified models viz. in vitro cell migration assay, ex vivo aortic ring assay, in vitro chick yolk sac membrane assay and in vivo matrigel plug xenograft model corroborating its anti-angiogenic potential and establishing the best means of evaluation.Results
Assorted models were reproducible and correlative to one another. DEAE-Dextran exhibited excellent anti-angiogenic effect in cell migration assay over a duration of 24 h compared to the vehicle control fibroblast cell line and aortic ring possessed an alleviated rate of sprouting when treated with DEAE-Dextran with contrast to vehicle control aorta. Similarly, decreased vascular density was observed in DEAE-Dextran treated chick embryos implicating potency of the β-interferon inducer. Augmenting to these results, the matrigel plugs also mitigated vascular net as well as reduced levels of angiogenic marker CD31.Conclusion
Substantially, DEAE-Dextran leads to anti-tumor activity through anti-angiogenic action and a combination of in vitro and in vivo model is vital for the judgement of anti-angiogenic potential since an in vitro model exempts mammalian-culture considerations. 相似文献13.
Takahiro Mizoguchi Hiroko Minakuchi Miyu Tanaka Kazuhiro Tsuruma Masamitsu Shimazawa Hideaki Hara 《Pharmacological reports : PR》2018,70(3):476-480
Background
VGF nerve growth factor inducible (VGF) is a neuropeptide which is expressed in neuronal cells and endocrine cells. VGF is induced by several neurotrophic factors. The expression level of VGF in patients with schizophrenia is increased in cerebrospinal fluid (CSF) and prefrontal cortex. In our previous study, we generated mice in which the expression level of VGF in the brain was increased. VGF-overexpressing mice exhibited abnormal behaviors including hyperactivity. However, it remains unknown whether VGF-overexpressing mice exhibit the endophenotype of schizophrenia and whether abnormal behaviors in these mice can be improved by antipsychotics.Methods
In the present study, we investigated schizophrenia-like behaviors and the responsiveness to antipsychotics in transgenic mice.Results
VGF-overexpressing mice (1) exhibited prepulse inhibition (PPI) impairment, (2) showed normalized hyperactivity following antipsychotic drug treatment, and (3) showed abnormal responsiveness to haloperidol.Conclusion
Upregulation of VGF may be implicated in the pathophysiology of schizophrenia and abnormalities of dopaminergic signaling. 相似文献14.
Yuichiro Amano Hiroko Yamakawa Kazuko Yonemori Mitsuyuki Shimada Ryuichi Tozawa 《Pharmacological reports : PR》2018,70(1):172-177
Background
The effects of farnesoid X receptor (FXR) antagonists on plasma lipid profile in mice have not been investigated thus far. The aim of this study was to investigate the antidyslipidemic effects of an FXR antagonist in dyslipidemic mice, and to clarify the mechanisms underlying the lipid modulatory effect.Methods
Compound-T0 (1–100?mg/kg) was orally administered to C57BL/6J mice fed a Western-type diet or low-density lipoprotein receptor knockout (LDLR-/-) mice fed a Western-type diet for a week, and plasma lipid levels were investigated. Effects on lipid clearance, hepatic triglyceride secretion after Triton WR-1339 challenge, and intestinal lipid absorption were investigated after multiple dosing.Results
Compound-T0 significantly increased plasma level of non-high-density lipoprotein cholesterol in both C57BL/6 and LDLR-/- mice; in addition, it significantly increased plasma triglyceride level in LDLR-/- mice. Compound-T0 failed to enhance the clearance of 3,3′-dioctadecylindocarbocyanine (DiI)-labeled LDL in C57BL/6J mice. Although compound-T0 did not affect triglyceride clearance and hepatic triglyceride secretion, it significantly increased intestinal [3H]cholesterol absorption in LDLR-/- mice.Conclusions
It was found that the FXR antagonist, compound-T0 exacerbated dyslipidemia in mice because it enhanced intestinal lipid absorption via acceleration of bile acid excretion. 相似文献15.
An-Kuo Chou Chong-Chi Chiu Yu-Wen Chen Jhi-Joung Wang Ching-Hsia Hung 《Pharmacological reports : PR》2018,70(6):1180-1184
Background
Pramoxine has been shown to produce spinal anesthesia, while cutaneous analgesia (peripheral) of pramoxine is not established. The experimental goal was to examine cutaneous antinociception produced by a local anesthetic (LA) pramoxine and compare this result with that of another well-known LA lidocaine.Methods
Cutaneous antinociception was evaluated by blockade of pinprick- induced cutaneous trunci muscle reflex (CTMR) on the skin of rat's back. After the dose–related curves were constructed, the quality and duration of drug's (lidocaine and pramoxine) cutaneous antinociception were compared.Results
We showed that pramoxine, as well as lidocaine produced skin antinociception in a dose–related fashion. The relative potency (ED50 [50% effective dose] basis) was lidocaine (5.44 [4.67–6.35] μmol) greater than pramoxine (42.1 [38.8–45.7] μmol) (p < 0.01). On the basis of equianalgesic doses (ED75, ED50, and ED25), pramoxine caused equivalent duration of cutaneous antinociception to lidocaine.Conclusions
These preclinical data indicated that pramoxine elicits skin antinociception dose-relatedly. Pramoxine exhibits a potency less than that of lidocaine while they have a comparable duration of skin antinociceptive action. 相似文献16.
Ryszard Pluta Anna Bogucka-Kocka Marzena Ułamek-Kozioł Jacek Bogucki Sławomir Januszewski Janusz Kocki Stanisław J. Czuczwar 《Pharmacological reports : PR》2018,70(5):881-884
Background
Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimer’s disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations.Methods
We have investigated the relationship between hippocampal ischemia and Alzheimer’s disease by means of a transient 10-min global brain ischemia in rats and determining the effect on Alzheimer’s disease tau protein gene expression during 2, 7 and 30?days post injury.Results
We found the significant overexpression of tau protein gene on the 2nd day, but on day’s 7 and 30 post-ischemia there a significant opposite tendency was observed.Conclusion
The obtained results offer a novel insight into tau protein gene in regulating delayed neuronal death in the ischemic hippocampus. Finally, these findings further elucidate the long-term impact of brain ischemia on Alzheimer’s disease development. 相似文献17.
Naeima Eftekhar Ali Moghimi Mohammad Hossein Boskabady 《Pharmacological reports : PR》2018,70(1):119-125
Background
Rosmarinic acid (RA) as an active component of several medicinal plants, has shown anti-inflammatory and anti-oxidant effects. In this study, the effect of RA on tracheal responsiveness (TR), lung inflammatory cells, oxidant biomarkers in sensitized rats were evaluated.Methods
TR to methacholine and ovalbumin (OVA) as well as total and differential white blood cell (WBC) count and levels of nitrogen dioxide, nitrate, malondialdehyde, thiol, superoxide dismutase, and catalase in bronchoalveolar lavage fluid were measured in control (group?C) rats, sensitized animals to OVA and given drinking water alone (group S), S groups receiving drinking water containing three concentrations of RA (0.125, 0.250 and 0.500?mg/mL) and dexamethasone (1.25?μg/mL), (n?=?6 in each group).Results
Increased TR to methacholine and OVA, total WBC count, percentages of eosinophils, monocytes, neutrophils and levels of oxidant biomarkers but decreased other measured parameters were observed in group S compared to group C. Percentages of lymphocytes and antioxidant biomarkers were significantly increased but other measured parameters were significantly decreased in S group treated with dexamethasone and in rats treated with the two higher concentrations of RA compared to S group. The effect of RA medium concentration on percentage of eosinophils and RA high concentration on total WBC count and percentages of eosinophils and lymphocytes, were significantly higher than those of dexamethasone.Conclusion
These results showed the concentration-dependent effect of RA on tracheal responses, lung inflammatory cells and oxidant-antioxidant parameters which was comparable to that of dexamethasone at used concentrations in sensitized rats. 相似文献18.
Background
Ifenprodil as a specific antagonist of NMDA receptors containing a dominant NR2B subunit exhibits age-dependent anticonvulsant action. Possible changes of this action due to status epilepticus (SE) elicited at early stage of development were studied using cortical epileptic afterdischarges (ADs) as a model.Methods
Lithium-pilocarpine SE was induced at postnatal day 12 and effects of ifenprodil were studied 3, 6, 9, and 13?days after SE in rat pups with implanted epidural electrodes. Controls (LiPAR) received saline instead of pilocarpine. ADs were elicited by low frequency stimulation of sensorimotor cortex. Intensity of stimulation current increased in 18 steps from 0.2 to 15?mA. Ifenprodil (20?mg/kg) was administered intraperitoneally (ip) after the stimulation with 3.5-mA current. Threshold for four different phenomena as well as duration of ADs were evaluated.Results
The threshold for the transition into the limbic type of ADs was higher in 15-day-old SE rats than in LiPAR controls. Opposite difference was found in 18-day-old animals, older rats did not exhibit any difference. Isolated significant changes in total duration of ADs were found after high stimulation intensities. These changes appeared in 18-day-old rats where ADs were shorter in SE than in control LiPAR rats.Conclusions
Changes in ifenprodil action were found only in the first week after SE but not in the second week. Interpretation of the results is complicated by failure of significant differences between SE and LiPAR rats probably due to a high dose of paraldehyde. 相似文献19.
Marta Jóźwiak-Bębenista Magdalena Jasińska-Stroschein Edward Kowalczyk 《Pharmacological reports : PR》2018,70(5):1032-1039
Background
Recent evidence suggests that the mitogen activated protein kinase (MAPK)-associated signaling pathway in the frontal cortical areas demonstrates abnormal activity in cases of schizophrenia. Moreover, schizophrenia patients often display alterations in the regional cellular energy metabolism and blood flow of the brain; these are shown to parallel changes in angiogenesis primarily mediated by vascular endothelial growth factor (VEGF).Methods
The present study examines the differential effects of time-dependent treatment with haloperidol, olanzapine and amisulpride (20 μM) on VEGF and MAPK mRNA expression and VEGF level, using the T98 cell line as an example of nerve cells. For the purposes of comparison, the effect of neuroprotective pituitary adenylate cyclase-activating polypeptide (PACAP) on the expression of VEGF mRNA and secretion were also evaluated in this cell model.Results
RT-PCR analysis revealed that all the tested neuroleptics increased VEGF mRNA expression after 72-h incubation; however, only haloperidol and olanzapine also increased the level of VEGF detected by ELISA, and they demonstrated significantly stronger effects than PACAP. Haloperidol and olanzapine, but not amisulpride, decreased MAPK14 mRNA expression in T98G cells after 72-h incubation.Conclusion
The obtained results suggest that haloperidol and olanzapine can trigger the MAPK and VEGF signaling pathway, which may contribute to their neuroprotective mechanism of action. 相似文献20.
Tomasz Kocki Ewa M. Urbańska Janusz Kocki Renata Kloc Katarzyna Kocka Marcin Olajossy Björn Owe-Larsson 《Pharmacological reports : PR》2018,70(4):737-745