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1.
Patrycja Nowicka-Stążka Ewa Langner Waldemar Turski Wojciech Rzeski Jolanta Parada-Turska 《Pharmacological reports : PR》2018,70(2):277-283
Background
Previously, we have demonstrated that kynurenic acid (KYNA), an endogenous metabolite of tryptophan formed along kynurenine pathway, is present in synovial fluid of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. In this study, the goal was to investigate the presence of quinaldic acid (QUDA), a putative metabolite of KYNA, in synovial fluid of RA and OA patients.Methods
The effect of QUDA on proliferation and motility of synovial fibroblasts and its interaction with KYNA were determined in vitro. The study was conducted on synovial fluid obtained from 38 patients with RA and 15 patients with OA. QUDA was identified and quantified using the gas chromatography–mass spectrometry (GC–MS) method. In vitro experiments were conducted on rabbit synoviocyte cell line HIG-82.Results
Presence of QUDA was detected in all 53 samples of synovial fluid. The concentration of QUDA in synovial fluid obtained from patients with RA was 28.6?±?14.9?pmol/ml, which was lower in comparison with OA 42.3?±?10.0?pmol/ml. QUDA content positively correlated with the number of tender joints and negatively with the total cell counts determined in synovial fluid of RA patients. It did not correlate with KYNA content. QUDA reduced both proliferation and motility of synoviocytes in a dose-dependent manner. The enhancement of antiproliferative action of QUDA by KYNA was evidenced.Conclusions
Data show a local deficit of QUDA in RA patients and suggest its potential role as an endogenous substance controlling synoviocyte viability. 相似文献2.
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3.
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4.
Michał Seweryn Karbownik Paweł Gunerka Paweł Turowski Maciej Wieczorek Edward Kowalczyk Wojciech Łężak Tadeusz Pietras 《Pharmacological reports : PR》2018,70(2):346-349
Background
Catalytic subunit delta of phosphoinositide 3-kinase, p110δ, encoded by the PIK3CD gene, was recently proposed as a target for pharmacological treatment of schizophrenia. Current antipsychotic drugs were found to decrease the mRNA expression of PIK3CD, but the mechanism of this process is not known. The aim of the study was to elucidate the mechanism by which antipsychotic drugs affect the mRNA expression of PIK3CD.Methods
The direct effect of haloperidol, clozapine, olanzapine, quetiapine and amisulpride on p110δ enzymatic activity was tested with a kinase assay, and the results were referenced against data on the mRNA expression of PIK3CD.Results
Haloperidol, clozapine, olanzapine and quetiapine, but not amisulpride, at the concentration of 20–80?μM, were found to significantly increase enzymatic activity of p110δ by up to two times in a dose-dependent manner. Linear regression analysis revealed that more than 40% of the variance in antipsychotic drugs-induced changes in the expression of PIK3CD mRNA was explained only by changes in antipsychotic drug-regulated p110δ enzymatic activity (p?=?0.011).Conclusions
Antipsychotic drugs differentially increase the enzymatic activity of p110δ. This effect is associated with that of mRNA expression of the PIK3CD gene. Drug-enzyme interaction may explain the effect of antipsychotic drugs on the expression of PIK3CD mRNA, however, further studies are needed to investigate this hypothesis. 相似文献5.
Meizhi Wang Hui Gao Haijun Qu Jing Li Kaili Liu Zhiwu Han 《Pharmacological reports : PR》2018,70(5):963-971
Background
The most frequent type of renal cell carcinoma is called clear-cell renal cell carcinoma (ccRCC) which is associated with a poor prognosis. It has been observed that miR-137 is aberrantly expressed in many different kinds of human malignancies including ccRCC. This research aims to examine the role of miR-137 in ccRCC.Methods
Quantitative RT-PCR (qRT-PCR) was applied to measure miR-137 expression in ccRCC and adjacent noncancerous tissue. Gene expression was determined by western blot. Cell Counting Kit-8 (CCK-8) assay, flow cytometry and Transwell assay were used to determine the effects of miR-137 on cell growth, apoptosis and invasion, respectively. Moreover, xenograft and pulmonary metastasis animal models were established to investigate the role of miR-137 in vivo.Results
Our findings show that there was significant downregulation of miR-137 in ccRCC tissue relative to corresponding non-cancerous tissue. Ectopic miR-137 expression in ccRCC cells led to suppression of cell growth and invasion, as well as apoptosis induction. In contrast, knockdown of miR-137 enhances proliferation and invasion, inhibits apoptosis. It also confirms that miR-137 plays a tumor supressor role in vivo. Mechanically, miR-137 directly targets the 3′-UTR of RLIP76 which is an established oncogene in ccRCC.Conclusion
MiR-137 serves as a tumor suppressor, which can be considered a potential therapeutic target in ccRCC. 相似文献6.
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7.
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8.
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9.
Hanaa Mahmoud Ali 《Pharmacological reports : PR》2018,70(4):804-811
Background
Lead acetate (Led) and mercury chloride (Mer) represent important ecological and public health concerns due to their hazardous toxicities. Naturally found products play a vital role in chemopreventive agent innovation. The current study aimed to assess the modifying effect of garlic (Gar) and/or vitamin E (Vit E) against the half-maximal inhibitory concentration (IC50) Led and/or Mer-induced cytotoxic, genotoxic and apoptotic effects.Methods
Human lung cells (WI-38) were pretreated with Gar and/or Vit E for 24 h and then treated with Led and/or Mer either alone or with their combination for 24 h. Cytotoxicity of Led and Mer and the viability of Gar and Vit E were assessed using MTT assay. The alkaline comet assay was used to assess DNA damage, whereas QRT-PCR was performed to evaluate p53, Bax, and Bcl2 mRNA-expression.Results
The results of this study showed that IC50 of Led was (732.72 μg/mL) and for Mer was (885.83 μg/mL), while cell viability effective dose for Gar was (300 μg/mL) and for Vit E was (26,800 μg/mL). Treating cells with the IC50-concentration of Led or Mer or their combination using half IC50 of both of them induced severe DNA-damage. Bax-expression was increased, while p53 and Bcl2-expressions were decreased. Pretreatment of cells with Gar and/or Vit E ameliorated the previous alternations.Conclusions
Led and Mer can induce oxidative stress and change the expressions of apoptosis-related proteins in WI-38 cells. Gar and Vit E may be promising protective candidate agent against the toxic effect of heavy metals. 相似文献10.
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11.
Zülbiye Yılmaz Esra Betül Kalaz A. Fatih Aydın Vakur Olgaç Semra Doğru-Abbasoğlu Müjdat Uysal Necla Koçak-Toker 《Pharmacological reports : PR》2018,70(3):584-590
Background
Methylglyoxal (MG) is a highly reactive dicarbonyl compound. It is produced by processes like glycolysis, glucose autooxidation, lipid peroxidation, and protein glycation. It is a major precursor of advanced glycation end products (AGE). It also exacerbates oxidative stress in the organism. Although there are some in vitro studies investigating the effect of resveratrol (RES) as an antioxidant and antiglycating agent on MG-induced toxicity, in vivo effect of RES is unknown. Therefore, we aimed to investigate the efficiency of RES in chronic MG-treated rats.Methods
Rats were given incrementally increased doses (100–300?mg/kg) of MG in drinking water for ten weeks. RES (10?mg/kg ip) was administered together with MG. Reactive oxygen species (ROS) formation, thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels as well as ferric reducing antioxidant power (FRAP) values were determined in plasma and liver.Results
Significant increases in plasma TBARS, PC, AOPP and AGE and fructosamine levels were detected in MG-treated rats. However, plasma ROS and FRAP levels remained unchanged. Hepatic ROS, TBARS, PC and AOPP, but not AGE and FRAP levels were also increased in MG-treated rats. RES treatment diminished high levels of plasma PC, AOPP and AGE levels in MG-treated rats. Additionally, significant decreases in hepatic ROS, TBARS, PC and AOPP levels together with histopatological amelioration were detected due to RES treatment in MG-treated rats.Conclusions
Our results indicate that RES may be considered as a protective agent against glycoxidative stress generated by in vivo MG treatment. 相似文献12.
13.
Nersi Jafary Omid Nika Bahari Javan Ahmad-Reza Dehpour Alireza Partoazar Morteza Rafiee Tehrani Farid Dorkoosh 《International journal of pharmaceutics》2018,535(1-2):293-307
Purpose
The aim of this research work was to explore the possibility of providing multifunctional oral insulin delivery system by conjugating several types of dipeptides on chitosan and trimethyl chitosan to be used as drug carriers.Method
Conjugates of Glycyl-glycine and alanyl-alanine of chitosan and trimethyl chitosan (on primary alcohol group of polymer located on carbon 6) were synthesized and nanoparticles containing insulin were prepared for oral delivery. Preparation conditions of nanoparticles were optimized and their performance to enhance the permeability of insulin as well as cytotoxicity of nanoparticles in Caco-2 cell line was evaluated. To evaluate the efficacy of orally administered nanoparticles, nanoparticles with the most permeability enhancing ability were studied in male Wistar rats as animal model by measuring insulin and glucose Serum levels.Result
Structural study of all the conjugates by infrared spectroscopy and nuclear magnetic resonance confirmed the successful formation of the conjugates with the desirable substitution degree. By optimizing preparation conditions, nanoparticles with expected size (157.3–197.7?nm), Zeta potential (24.35–34.37?mV), polydispersity index (0.365–0.512), entrapment efficiency (70.60–86.52%) and loading capacity (30.92–56.81%), proper morphology and desirable release pattern were obtained. Glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan showed 2.5–3.3 folds more effective insulin permeability in Caco-2 cell line than their chitosan counterparts. In animal model, oral administration of glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan demonstrated reasonable increase in Serum insulin level with relative bioavailability of 17.19% and 15.46% for glycyl-glycine and alanyl-alanine conjugate nanoparticles, respectively, and reduction in Serum glucose level compared with trimethyl chitosan nanoparticles (p?<?0.05).Conclusion
It seems that glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan have met the aim of this research work and have been able to orally deliver insulin with more than one mechanism in animal model. Hence, they are promising candidates for further research studies. 相似文献14.
Daohua Shi Peiguang Niu Xiaojie Heng Lijun Chen Yanting Zhu Jintuo Zhou 《Pharmacological reports : PR》2018,70(5):908-916
Background
The mammalian target of rapamycin (mTOR) integrates energy level to modulate cell proliferation and autophagy. Cardamonin exhibits anti-proliferative activity through inhibiting mTOR. In this study, the effect of cardamonin on autophagy and its mechanism on mTOR inhibition were investigated.Methods
Cell viability and proliferation were measured by MTT assay and BrdU incorporation, respectively. Cell apoptosis was assayed by flow cytometry and cell autophagy was detected by electron microscopy and GFP-LC3 fluorescence. The mechanism of cardamonin on mTORC1 inhibition was investigated by Raptor siRNA and Raptor over-expression.Results
The cell viability and proliferation were inhibited by cardamonin. The autophagosomes and the protein level of LC3-II were increased by cardamonin. Cell apoptosis and the levels of cleaved PARP and Caspase-3 were increased by cardamonin. Cardamonin inhibited the phosphorylation of mTOR and ribosome S6 protein kinase 1 (S6K1) as well as the protein level of regulatory associated protein of mTOR (Raptor). However, cardamonin had no effect on the component of mTORC2 and its downstream substrate Akt. The inhibitory effect of cardamonin on the phosphorylation of mTOR and S6K1 was eliminated by Raptor knockdown with siRNA, whereas this effect of cardamonin was stronger than that of rapamycin and AZD8055 in Raptor over-expression cells. Cell viability was inhibited by cardamonin in both Raptor knockdown and Raptor over-expression cells, which was consistent with the inhibitory effect of cardamonin on mTOR.Conclusion
These findings demonstrated that the autophagy induced by cardamonin was associated with mTORC1 inhibition through decreasing the protein level of Raptor in SKOV3 cells. 相似文献15.
Amrita A. Chowdhury Nitin B. Gawali Vipin D. Bulani Pankaj S. Kothavade Snehal N. Mestry Padmini S. Deshpande Archana R. Juvekar 《Pharmacological reports : PR》2018,70(2):372-377
Background
Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) plaques, neurofibrillary tangles (NFTs) and cognitive impairment. Literature cites the role of advanced glycation end products (AGEs) in AD due to increased cytotoxicity via oxidative stress. d-galactose (d-gal) induced amnesia stimulates Aβ overproduction via increased oxidative stress and AGEs. Trigonelline (TRG), a naturally occurring alkaloid has been reported to have neuroprotective and antidiabetic properties.Methods
Present study assessed the protective effect of TRG against in vitro AGEs formation. Since chronic administration of d-gal increases AGEs, we subsequently investigated the neuroprotective role of TRG (50 and 100?mg/kg as per body weight) against d-gal induced amnesia. Mice were subcutaneously (sc) injected with d-gal (150?mg/kg) for 6 weeks. Behavioral assessments in Morris water maze (MWM) and Y-maze were performed, followed by biochemical estimations to deduce the probable mechanism of action.Results
In vitro experiments demonstrated that TRG stalled early and late AGEs formation. Chronic d-gal administration significantly impaired cognitive performance in MWM and Y maze, caused marked oxidative damage, elevated the AGEs levels and significantly increased the acetylcholinesterase levels as compared to sham group. TRG (50 and 100?mg/kg) treatment significantly ameliorated cognitive performance, reversed the oxidative damage, decreased AGE levels and caused significant decline in acetylcholine esterase levels as compared to d-gal group.Conclusion
Present study highlights the neuroprotective role of TRG against d-gal induced amnesia due to the antioxidant, antiglycative and anticholinesterase properties. 相似文献16.
Ana Carla A. Souza Fabíula F. Abreu Lúcio R.L. Diniz Renata Grespan Josimari M. DeSantana Lucindo J. Quintans-Júnior Paula P. Menezes Adriano A.S. Araújo Cristiane B. Correa Simone A. Teixeira Marcelo N. Muscará Soraia K.P. Costa Enilton A. Camargo 《Pharmacological reports : PR》2018,70(6):1139-1145
Background
Skeletal muscle inflammation is strongly associated with pain and may impair regeneration and functional recovery after injury. Since anti-inflammatory and antinociceptive effects have been described for the inclusion complex of carvacrol and β-cyclodextrin (βCD-carvacrol), this study investigated the effects of βCD-carvacrol in a model of acute skeletal muscle inflammation.Methods
Muscle injury was induced in male Wistar rats by injection of 3% carrageenan in the gastrocnemius muscle. Rats were orally pretreated with saline (vehicle) or βCD-carvacrol (20, 40, 80 and 180?mg/kg) one hour before administration of carrageenan.Results
The injection of carrageenan in the gastrocnemius muscle increased tissue myeloperoxidase (MPO) activity (p?<?0.001), edema (p?<?0.001) and the levels of tumoral necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, macrophage inflammatory protein (MIP-2), but not IL-10 levels. Also, it increased mechanical hyperalgesia and decreased the grip force of animals. Pretreatment with βCD-carvacrol (80 or 160 mg/kg) significantly decreased muscle MPO activity and edema 24 h after injury in comparison to vehicle-pretreated group. Animals pretreated with βCD-carvacrol (160 mg/kg) presented significantly lower levels of IL-1β, IL-6 and MIP-2 and higher levels of IL-10 six hours after induction and lower levels of TNF-α and MIP-2 after 24 h when compared to the vehicle group. Pretreatment with βCD-carvacrol also reduced mechanical hyperalgesia and limited the decrease of grip force (80 or 160 mg/kg; p?<?0.001) 6 and 24 h after injury.Conclusion
These results show that βCD-carvacrol reduces inflammation and nociception in a model of acute injury to skeletal muscles. 相似文献17.
Background
Oxytocin plays an important role in supraspinal modulation of pain. In the present study, we investigated the effects of ventrolateral orbital cortex (VLOC) microinjection of oxytocin on neuropathic pain after blockade of opioid receptors in this area and ventrolateral periaqueductal gray (vlPAG).Methods
Neuropathic pain was induced by complete transcection of preoneal and tibial branches of sciatic nerve. The VLOC and vlPAG were unilaterally (contralateral to the sciatic nerve-injured side) and bilaterally implanted with guide cannulas, respectively. Mechanical paw withdrawal threshold (PWT) was measured using von Frey filaments. Area under curve (AUC) was also calculated.Results
Microinjection of oxytocin (5, 10 and 20?ng/site) into the VLOC increased PWT. Antiallodynia induced by oxytocin (20?ng/site) was inhibited by prior intra-VLOC administration of atosiban (an oxytocin receptor antagonist, 100?ng/site) and naloxone (an opioid receptor antagonist, 500?ng/site). Prior microinjection of naloxone (500?ng/site) into the vlPAG also inhibited antiallodynia induced by intra-VLOC microinjection of oxytocin (20?ng/site). All the VLOC and vlPAG microinjected drugs did not alter locomotor activity.Conclusions
It is concluded that oxytocin and its receptor may be involved in modulation of neuropathic pain at the VLOC level. Opioid receptors of VLOC and vlPAG might be involved in the antiallodynic effect of the VLOC-microinjected oxytocin. 相似文献18.
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19.
Anna Bejrowska Monika Pawłowska Anna Mróz Zofia Mazerska 《Pharmacological reports : PR》2018,70(3):470-475
Background
Among the studied antitumor acridinone derivatives developed in our laboratory, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) and 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) exhibited cytotoxic and antitumor properties against several cancer types and were selected to be evaluated in preclinical and early-phase clinical trials. In the present work, we investigated the impact of C-1305 and C-1311 on UDP-glucuronosyltransferase (UGT) activity.Methods
Enzyme activity modulation was studied using HPLC by analyzing standard UGT substrate metabolism in the presence and absence of antitumor drugs. The investigations were performed in two model systems: (i) under noncellular conditions, including human liver microsomes (HLM) and recombinant UGT1A1, 1A9 and 1A10 isoenzymes and (ii) in tumor cells.Results
There was observed a slight impact of studied drugs on enzyme activity. Only UGT1A1 action was altered by both compounds. The modulatory effects of UGT activity in cellular systems depended on the tumor cell type. In the case of HepG2, C-1305 and C-1311 strongly induced UGT activity, particularly for C-1311, at concentrations significantly lower than the EC50. This effect contradicted irinotecan mediated UGT inhibition. HT29 colon tumor cells were less sensitive than HepG2 to enzyme modulation in the presence of the studied compounds, particularly C-1305, where enzymatic inhibition similar to that of irinotecan was observed.Conclusions
The results demonstrated that UGT activity modulation should be expected in the case of antitumor therapy with C-1305 or/and C-1311. Analysis of the results indicated that these modulations would occur via cellular regulatory pathways not by direct drug-enzyme interactions. 相似文献20.
Faisal Imam Naif O. Al-Harbi Mohammad Matar Al-Harbi Mushtaq Ahmad Ansari Abdullah F Al-Asmari Mohd Nazam Ansari Wael A. Al-Anazi Saleh Bahashwan Mashal M Almutairi Musaad Alshammari Mohammad Rashid Khan Abdulaziz Mohammed Alsaad Moureq Rashed Alotaibi 《Pharmacological reports : PR》2018,70(5):993-1000