共查询到20条相似文献，搜索用时 31 毫秒
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.
Tomasz Kocki Ewa M. Urbańska Janusz Kocki Renata Kloc Katarzyna Kocka Marcin Olajossy Björn Owe-Larsson 《Pharmacological reports : PR》2018,70(4):737-745
Background
Accumulating data suggest an important role of disturbed kynurenine pathway and altered glutamatergic transmission in the pathogenesis of depression. In here, we focused on detailed analyses of kynurenic acid (KYNA) status in vivo following single and 14-day administration of selected tricyclic antidepressant drugs (TCAs) and serotonin selective reuptake inhibitors (SSRIs) in rats.Methods
The effect of antidepressants on serum and brain KYNA levels, as well as on the activity of kynurenine aminotransferases (KATs I and II) and expression of Kat1 and Kat2 genes mRNA was studied in three brain regions.Results
Chronic, but not acute, application of antidepressants invariably stimulated KYNA production in hippocampus (amitriptyline, imipramine, fluoxetine and citalopram) and sporadically in cortex (amitriptyline, fluoxetine), whereas no change in KYNA level was observed in striatum. Cortical and hippocampal expression of Kat1 and Kat2 genes was increased after chronic, but not single administration of all studied antidepressants. The activity of semi-purified enzymatic proteins, KAT I and II, was not paralleling changes of Kat1 and Kat2 genes.Conclusion
Our data indicate that prolonged administration of antidepressants targets expression of KYNA biosynthetic enzymes. Furthermore, post-translational modulation of KATs seems to play an important role in tuning of KYNA synthesis within brain structures. We suggest that consistent increase of hippocampal KYNA levels may represent hallmark of antidepressant activity. Mechanisms governing region- and drug-selective action of antidepressants require further investigations. 相似文献3.
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4.
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5.
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6.
Włodzimierz Opoka Joanna Piotrowska Adam Krakowski Agata Kryczyk Kinga Sałat Małgorzata Zygmunt Tadeusz Librowski Bożena Muszyńska 《Pharmacological reports : PR》2018,70(4):684-687
Background
Zinc (Zn) is a micronutrient and essential element of life and its deficiency causes severe disorders of numerous body systems, such as immune, reproductive and central nervous system. Zinc supplementation affects wound healing and sexual development. The interactions between drugs administration and Zn level in tissues are not fully understood. The aim of the study was to demonstrate differences in Zn content in teeth of laboratory animals that have undergone pharmacological tests.Methods
The teeth were extracted from laboratory animals after chronic administration of a non-steroidal anti-inflammatory drug (8-[4-[4-(4-chlorophenyl) piperazine-1-sulfonylphenyl]]-1-propylxanthine), a steroid anti-inflammatory drug (deoxycorticosterone) and an anti-cancer drug (oxaliplatin used acutely). The method of flame atomic absorption spectrometry was used to determine the Zn content in the teeth of the laboratory animals.Results
Based on the studies conducted, the administration of the anti-inflammatory drug PSB-603 and deoxycorticosterone results in an increase in Zn accumulation in the teeth of laboratory animals, which may be indicative of the effect of anti-inflammatory drugs on the metabolism of this bioelement. Oxaliplatin has the opposite effect, after which the level of the measured bioelement in the teeth of mice depended on the administered dose. This level was on average 21.0–28.1% lower than the Zn level in the teeth of the control group. Anti-cancer drugs may interfere with Zn accumulation in the teeth and cause the removal of this metal from bone tissue.Conclusion
It can be assumed that the Zn content in teeth can be markedly affected by the drugs that were administrated to animals. 相似文献7.
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8.
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9.
Monu Yadav Milind Parle Deepak Kumar Jindal Sameer Dhingra 《Pharmacological reports : PR》2018,70(3):591-599
Background
Stigmasterol, a naturally occurring phytoestrogen has been reported to possess many pharmacological activities. The aim of the present study was to screen the effect of stigmasterol against ketamine-induced mice model of psychosis.Methods
The behavioural studies included an assessment of locomotor activity, stereotypic behaviours, immobility duration, step down latency and effects on catalepsy. Biochemical estimations involved the estimations of GABA, dopamine, GSH, MDA, TNF-α, total protein content and AChE activity. Histopathological changes and effect on androgenic parameters were also evaluated.Results
Stigmasterol treated animals showed significant decrease in locomotor activity, stereotypic behaviours, immobility duration and increased step down latency. Biochemical estimations revealed increased GABA, GSH levels and decreased dopamine, MDA, TNF-α levels and AChE activity. These findings were confirmed by histopathological changes in the cortex part of the brain. Further, stigmasterol was not found to cause catalepsy and any adverse effect on the reproductive system.Conclusion
This study concluded that stigmasterol could ameliorate ketamine-induced behavioral, biochemical and histopathological alterations in mice showing its potential effects in the management of psychotic symptoms. 相似文献10.
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11.
Elżbieta Gałecka Monika Talarowska Michael Maes Kuan-Pin Su Paweł Górski Anna Kumor-Kisielewska Janusz Szemraj 《Pharmacological reports : PR》2018,70(1):133-138
Background
Thyroid hormones (TH) are involved in modulation of the immune system and inflammation. TH dysregulation is associated with depressive disorders. The iodothyronine deiodinases (DIOs), the key enzymes for TH synthesis, can be affected and induced by pro-inflammatory cytokines. We aimed to investigate the levels of and correlation between type 2 DIO (DIO2) and interferon-gamma (IFN-?) in patients with recurrent depressive disorders (rDD).Methods
Data from 91 rDD patients and 105 healthy controls were analyzed. The diagnoses are based on the ICD-10 criteria (F33.0-F33.8). Expression levels of DIO2 and IFN-? were estimated using the method based on the polymerase chain reaction and the enzyme-linked immunosorbent assay (ELISA).Results
The DIO2 expression on mRNA/protein levels in rDD patients (both female and males) was reduced as compared with the control subjects. No correlation between DIO2 and IFN-? expression was observed.Conclusion
This is the first study to reveal that one may cautiously suggest that DIO2 may be involved in the development and/or progression of rDD. The mechanisms of TH regulation on depression, however, need further investigation. 相似文献12.
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13.
Alina Sesarman Lucia Tefas Bianca Sylvester Emilia Licarete Valentin Rauca Lavinia Luput Laura Patras Manuela Banciu Alina Porfire 《Pharmacological reports : PR》2018,70(2):331-339
Background
Emerging treatment options for colon cancer are needed to overcome the limitations regarding the side effects of current chemotherapeutics and drug resistance. The goal of this study was to assess the antitumor actions of PEGylated long-circulating liposomes (LCL) co-delivering curcumin (CURC) and doxorubicin (DOX) on murine colon carcinoma cells (C26).Methods
The cytotoxicity of CURC and DOX, administered alone or in combination, either in free or LCL form, was evaluated with regard to antiproliferative effects on C26 cells and to protumor processes that might be affected.Results
Our results indicated that PEGylated LCL-CURC-DOX exerted strong antiproliferative effects on C26 cells, slightly exceeding those induced by free CURC-DOX, but higher than either agent administered alone in their free form. These effects of LCL-CURC-DOX were due to the inhibition of the production of angiogenic/inflammatory proteins in a NF-κB-dependent manner, but were independent of ROS production or AP-1 c-Jun activation. Notable, the anti-angiogenic actions of LCL-CURC-DOX appeared to be much stronger than those induced by the co-administration of CURC and DOX in their free form, on C26 colon cancer cells.Conclusion
LCL-CURC-DOX demonstrated enhanced cytotoxicity on C26 murine colon cancer cells by inhibiting the production of the majority of factors involved in tumor-associated angiogenesis and inflammation and is now being evaluated in vivo regarding its efficacy towards tumor growth in colon cancer. 相似文献14.
José Luis Cortes-Altamirano Samuel Reyes-Long Adriana Olmos-Hernández Herlinda Bonilla-Jaime Paul Carrillo-Mora Cindy Bandala Alfonso Alfaro-Rodriguez 《Pharmacological reports : PR》2018,70(2):385-389
Background
Levetiracetam (LEV) is a novel anticonvulsant with proven antinociceptive properties. However, the antinociceptive and pronociceptive effect of this drug has not yet been fully elucidated in a tonic pain model.Methods
Thirty-six male rats (Wistar) were randomized into six groups and underwent the formalin test as follows: rats in the control group were administered 50 μL of 1% formalin in the paw; sham-group rats were administered 50 μL of saline in the paw to mimick the application of formalin; the four experimental groups were administered LEV intragastrically (ig) (50, 100, 200 and 300 mg/kg), and 40 min later 50 μL of 1% formalin was injected in the paw.Results
LEV exhibited antinociceptive effect in the 300 mg/kg LEV group (p < 0.05) and a pronociceptive effect in the 100 mg/kg LEV group (p < 0.05) and in the 50 mg/kg LEV group (p < 0.001).Conclusions
The antinociceptive and pronociceptive effect of LEV in a tonic pain model is dose-dependent. 相似文献15.
Akiyoshi Saitoh Hiromu Tominaga Yasuhiro Ogawa Yoko Irukayama-Tomobe Mitsuhiko Yamada Masashi Yanagisawa Hiroshi Nagase 《Pharmacological reports : PR》2018,70(2):350-354
Background
We previously reported that the novel selective delta opioid receptor (DOP) agonist KNT-127 did not cause convulsions in mice, whereas the prototype DOP agonist SNC80 did. Previous studies have reported that SNC80 caused electroencephalographic (EEG) disturbances in rodents. However, whether KNT-127 affects EEG responses is unknown. Therefore, the present study aimed to compare the effect of KNT-127 on EEG responses with that of SNC80 in mice.Methods
For behavioral experiments, male C57BL6/J mice were injected intraperitoneally with either KNT-127 (30?mg/kg) or SNC80 (30?mg/kg) and monitored for convulsions and subsequent catalepsy-like behavior for 10?min immediately after drug treatment. For EEG recording experiments, EEG electrodes were implanted into the right hemisphere. EEG signals exceeding twice the baseline amplitude were defined as seizure spikes.Results
KNT-127 did not induce convulsive or catalepsy-like behaviors in mice and did not result in seizure spikes, while significantly higher EEG power density was observed at 2?Hz. In contrast, SNC80 administration resulted in convulsive behaviors, seizure spikes, and significantly higher EEG power density between 2 and 10?Hz in mice.Conclusions
In this study, we clearly demonstrated that KNT-127 administration induces neither convulsive effects nor seizure spikes in mice. We propose that KNT-127 should be considered a candidate compound for the development of improved DOP-based psychotropic drug that lack the convulsive properties. 相似文献16.
Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels
Dragana P. Srebro Sonja M. Vučković Ivan S. Dožić Branko S. Dožić Katarina R. Savić Vujović Aleksandar P. Milovanović Branislav V. Karadžić Milica Š. Prostran 《Pharmacological reports : PR》2018,70(1):81-86
Background
In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain.Methods
Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum.Results
Magnesium sulfate administered subcutaneously (0.005–45 mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45 mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity.Conclusions
Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency. 相似文献17.
Background
Methylene-tetrahydrofolate reductase (MTHFR) gene variant may play an important role in the pathophysiology of diabetes and its complications due to its influence on plasma homocysteine levels and also its effect on scavenging peroxynitrite radicals. Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The aim of this study was to investigate the relationship between diabetic neuropathy and MTHFR gene C677T and 1298A ?C polymorphisms.Method
Patients with type 2 diabetes N = 248 were enrolled in the study, consisting of patients with neuropathy (N = 141) and patients without neuropathy (N = 107). MTHFR C677T polymorphism was analyzed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) of genomic DNA for genotyping of samples. 1298A/C polymorphism was evaluated using ARMS-PCR.Result
There was a significant difference in MTHFR polymorphism between the groups with and without neuropathy.Conclusion
Our results suggest that MTHFR 677 variant confer risk for diabetic neuropathy among Iranian patients with type 2 diabetes. 相似文献18.
Background
Parkinson’s disease (PD) is the most widespread motor-affecting disease affecting majorly middle- and late age population. Thus, in the current study, we intended to explore the neuroprotective effect of protodioscin (Proto) against 6-hydroxydopamine (6-OHDA)-induced PD rat model.Methods
After induction of PD with the injection of 6-OHDA, the different dose of Proto was administered for the duration of experimental protocol (2 months). We have scrutinized the consequence of Proto on the cognitive behaviours via Moris water maze (MWM), and recognition of novel objects and its location tasks. The effect of Proto was also investigated on the expression of Nrf2 in human neuroblastoma SHSY5Y cells via western blot analysis.Results
The results showed significant decrease in travelled distance as compared by the lesion treated group. Further significant difference was revealed in the latency time to detect the platform that is visible and it confirmed that, there were no noteworthy dissimilarity was observed in the visual and motor function ability. The result also suggests that, the activation of Nrf2 is the possible mechanism of neuroprotection of Proto against PD.Conclusion
As a concluding remark, the present study confirmed the neuroprotective role of Proto against PD both in in vitro and in vivo models. 相似文献19.
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20.
Takahiro Mizoguchi Hiroko Minakuchi Miyu Tanaka Kazuhiro Tsuruma Masamitsu Shimazawa Hideaki Hara 《Pharmacological reports : PR》2018,70(3):476-480