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1.
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2.
Hugo F. Miranda Fernando Sierralta Nicolas Aranda Paula Poblete Rodrigo L. Castillo Viviana Noriega Juan Carlos Prieto 《Pharmacological reports : PR》2018,70(3):503-508
Background
Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated.Methods
A dose–response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1β, glutathione and lipid peroxidation were measured at 7 and 14 days in PTX and PSNL murine models.Results
PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14 days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1β or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia.Conclusion
The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain. 相似文献3.
Ching-Hsia Hung Ja-Ping Shieh Chong-Chi Chiu Jhi-Joung Wang Yu-Wen Chen 《Pharmacological reports : PR》2018,70(3):565-569
Background
We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine.Methods
After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine.Results
We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED50)), the relative potency was bupivacaine (0.41 (0.36–0.48) mmol)> doxylamine (7.39 (6.91–7.91) mmol) (p < 0.01). On an equipotent basis (ED25, ED50 and ED75), subcutaneous doxylamine resulted in greater duration of action (p < 0.01) than bupivacaine at producing cutaneous analgesia.Conclusions
The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose. 相似文献4.
Hosein Pasandi Saman Abbaspoor Mohammad Naser Shafei Mahmoud Hosseini Abolfazl Khajavirad 《Pharmacological reports : PR》2018,70(5):1001-1009
Background
The pedunculopontine tegmental (PPT) nucleus is a heterogeneous nucleus with several functions including cardiovascular regulation. The presence of GABAA receptor has been shown in the PPT. Therefore, the cardiovascular effects of this receptor were examined.Methods
Rats were divided into: Control; Muscimol; Bicuculline (BMI); Hexamethonium (Hexa) + BMI and Atropine + BMI groups. The femoral vein and artery were cannulated for drug administration and recording of cardiovascular parameters, respectively. Muscimol (a GABAA agonist; 1.5 and 2.5 nmol), BMI (a GABAA antagonist; 0.1 and 0.2 nmol) were stereotaxically microinjected into the PPT. To evaluate the peripheral cardiovascular mechanisms of GABAA receptors, Hexa (a ganglionic blocker; 10 mg/kg) and atropine (a muscarinic receptor antagonist; 1 mg/kg) were intravenously (iv) injected before BMI (0.2 nmol). The average changes of mean arterial pressure (ΔMAP), systolic blood pressure (ΔSBP) and heart rate (ΔHR) in different intervals were calculated and compared both within and between case group and control group (repeated measures ANOVA). The peak changes in each group were also calculated and compared with those of the control group (independent sample t-test).Results
Both doses of BMI significantly increased ΔMAP, ΔSBP and ΔHR compared to control, while the only higher dose of muscimol significantly decreased ΔSBP. Iv injection of Hexa significantly attenuated ΔMAP, ΔSBP and ΔHR responses induced by BMI but atropine did not affect.Conclusions
Our results demonstrate that GABAA receptor of the PPT has a tonic inhibitory effect on the cardiovascular system and its peripheral effect mostly is mediated by sympathetic system. 相似文献5.
Agnieszka Karbownik Edyta Szałek Katarzyna Sobańska Agnieszka Klupczynska Szymon Plewa Tomasz Grabowski Anna Wolc Marta Moch Zenon J. Kokot Edmund Grześkowiak 《Pharmacological reports : PR》2018,70(2):191-195
Background
Diabetes mellitus (DM) is a complex metabolic disorder which affects the function of numerous tissues and alters the pharmacokinetic parameters of many drugs. As many oncological patients are diabetics, it is important to determine the influence of this chronic disease on the pharmacokinetics (PK) of anticancer drugs. Lapatinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The aim of the study was to compare the PK of lapatinib in normal and type 2 diabetes mellitus (T2DM) model rats. Additionally, the effect of lapatinib on blood glucose concentrations was examined.Methods
The PK of lapatinib was studied in healthy rats (n = 6, the healthy group) and T2DM model rats (n = 6, the diabetic group). The rats received lapatinib orally as a single dose of 50 mg. Plasma concentrations of lapatinib were measured with high-performance liquid chromatography method coupled with a tandem mass spectrometry.Results
The plasma concentrations of lapatinib were increased in the T2DM model rats. There were statistically significant differences between the groups in Cmax (p = 0.0104) and AUC0-t (p = 0.0265). The reduction of glycaemia in the range of 1.2–41.5% and in the range of 4.1–36.8% was observed in the diabetic and healthy animals, respectively.Conclusions
Higher concentrations of lapatinib in the diabetic rats may suggest the need for application of lower doses of this TKI in patients with DM. 相似文献6.
Piotr Tutka Aleksandra Wlaź Magdalena Florek-Łuszczki Patrycjusz Kołodziejczyk Dorota Bartusik-Aebisher Jarogniew J. Łuszczki 《Pharmacological reports : PR》2018,70(1):106-109
Background
Recent evidence reveals therapeutic potential for cannabinoids to reduce seizure frequency, severity and duration. Animal models are useful tools to determine the potential antiseizure or antiepileptic effects of cannabinoids. The objective of this study was evaluation of the effect of arvanil, olvanil, AM 1172 and LY 2183240, the compounds interacted with endocannabinoid and/or endovanilloid systems, on convulsions in the commonly used model of convulsions in mice.Methods
Arvanil and olvanil were injected intraperitoneally (ip) 30 min and AM 1172 and LY 2183240 were administered ip 60 min before the maximal electroshock seizure threshold (MEST) test. The criterion for convulsant activity was tonic hindlimb extension.Results
Arvanil, olvanil, AM 1172 and LY 2183240 dose-dependently increased the electroconvulsive threshold in mice. The TID20 (threshold increasing dose 20) values for arvanil, olvanil, AM 1172 and LY 2183240 were 0.9, 2.18, 2.48 and 3.56 mg kg?1, respectively, and the TID50 (threshold increasing dose 50) values were 1.88, 6.45, 6.29 and 10.04 mg kg?1, respectively.Conclusion
This study identified anticonvulsant effects of arvanil, olvanil, AM 1172 and LY 2183240. The order of the magnitude of the anticonvulsant effects of the examined compounds was following: arvanil > olvanil > AM 1172 > LY 2183240. 相似文献7.
Carlos Eduardo de Souza Menezes Roger S. McIntyre Adriano José Maia Chaves Filho Silvânia Maria Mendes Vasconcelos Francisca Cléa Florenço de Sousa João Quevedo Thomas N. Hyphantis André F. Carvalho Danielle Macêdo 《Pharmacological reports : PR》2018,70(6):1173-1179
Background
The use of antidepressants in combination is common practice following non-response to single antidepressant agents. Nevertheless, the scientific literature lacks preclinical studies regarding the combined administration of antidepressants across multiple behavioral measures including, but not limited to, cognition. Hence, we aimed to determine the effects of paroxetine (PAR), venlafaxine (VEN) and bupropion (BUP) alone or combined (PAR + BUP or VEN + BUP) on spatial and affective memory tasks to advance the knowledge about the combined use of antidepressants in cognition.Methods
Adult rats received daily injections (15 days) of PAR (20 mg/kg, ip), VEN (20 mg/kg, ip), BUP (20 mg/kg, ip) alone or combined and were submitted to behavioral measures of spatial memory (radial-arm maze - RAM), aversive memory (passive avoidance - PA), open field (OF) and forced swimming (FST) tests.Results
In the RAM, VEN or VEN + BUP impaired learning, while short-term memory (STM) was impaired by PAR, BUP and their combination. VEN + BUP improved STM as compared to BUP. PAR impaired long-term memory (LTM). VEN or BUP alone impaired STM and long-term fear memory, whilst PAR + BUP or VEN + BUP did not induce significant alterations.Conclusions
The effects of VEN, PAR or BUP alone and in combination on measures of memory are variable and vary as a function of the pharmacodynamics profile of each drug as well as the specific memory paradigm. 相似文献8.
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
Background
Doxorubicin is an effective, potent and commonly used anthracycline-related anticancer drug; however, cardiotoxicity compromises its therapeutic potential. Apremilast, a novel phosphodiesterase type 4-inhibitor, reported to have anti-inflammatory effects and modulating many inflammatory mediators.Methods
The present study investigated the influence of apremilast against doxorubicin-induced cardiotoxicity in male Wistar rats. A total, 24 animals were divided into four groups of six animal each. Group 1, served as control and received normal saline. Group 2 animals, received doxorubicin (20 mg kg?1, ip). Group 3 and 4, treatment group, received doxorubicin (20 mg kg?1, ip) with the same schedule as group-2, plus apremilast (10 and 20 mg kg?1 day?1, po) respectively. Oxidative stress, caspase-3 enzyme activity, gene expression and protein expression were tested.Results
The results of the present study demonstrated that administration of apremilast reversed doxorubicin-induced cardiotoxicity.Conclusion
These findings suggested that apremilast can attenuate doxorubicin-induced cardiotoxicity via inhibition of oxidative stress mediated activation of nuclear factor-kappa B signaling pathways. 相似文献9.
Elvia Mena-Avila Ricardo Márquez-Gómez Guillermo Aquino-Miranda Gustavo Nieto-Alamilla José-Antonio Arias-Montaño 《Pharmacological reports : PR》2018,70(1):146-155
Background
Clobenpropit, a potent antagonist/inverse agonist at the histamine H3 receptor (H3R), reduced the cytotoxic action of 6-hydroxydopamine (6-OHDA) in neuroblastoma SH-SY5Y cells transfected with the human H3R. We therefore set out to study whether this effect involved a receptor-independent action on dopamine transport.Methods
The uptake of [3H]-dopamine was assayed in SH-SY5Y cells and rat striatal or cerebro-cortical isolated nerve terminals (synaptosomes). Clobenpropit binding to the human norepinephrine (NET) and dopamine (DAT) transporters was analyzed by molecular modeling.Results
In SH-SY5Y cells, [3H]-dopamine uptake was inhibited by desipramine (selective NET inhibitor), GBR-12909 (selective DAT inhibitor), and fluoxetine (selective inhibitor of the serotonin transporter, SERT) with IC50 values 37, 537, and 2800 nM, respectively. The potency rank order indicates that [3H]-dopamine uptake is primarily performed by NET. Clobenpropit inhibited [3H]-dopamine uptake (maximum inhibition 82.7 ± 2.8%, IC50 490 nM), and the effect was reproduced by the H3R antagonist/inverse agonist iodophenpropit, but not by the agonists R-α-methylhistamine and immepip or the antagonists/inverse agonists ciproxifan and A-331440. Clobenpropit also inhibited [3H]-dopamine uptake by rat striatal and cerebro-cortical synaptosomes (?54.6 ± 11.3% and ?46.3 ± 9.6%, respectively, at 10 μM). Modeling of the human NET and DAT obtained by homology from the crystal of Drosophila melanogaster DAT showed that clobenpropit can bind to a site also recognized in both transporters by nisoxetine, a potent NET inhibitor.Conclusion
These data indicate a direct inhibitory effect of clobenpropit on catecholamine transport. 相似文献10.
Anna Mróz Izabela Ryska Hanna Sominko Anna Bejrowska Zofia Mazerska 《Pharmacological reports : PR》2018,70(5):972-980
Background
The compound 9-(2′-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), the promising antitumor agent developed in our laboratory was determined to undergo phase I metabolic pathways. The present studies aimed to know its biotransformation with phase II enzymes – UDP-glucuronosyltransferases (UGTs) and its potential to be engaged in drug-drug interactions arising from the modulation of UGT activity.Methods
UGT-mediated transformations with rat liver (RLM), human liver (HLM), and human intestine (HIM) microsomes and with 10 recombinant human isoenzymes were investigated. Studies on the ability of C-1748 to inhibit UGT were performed with HLM, HT29 colorectal cancer cell homogenate and the selected recombinant UGT isoenzymes. The reactions were monitored using HPLC-UV/Vis method and the C-1748 metabolite structure was determined with ESI-TOF-MS/MS analysis.Results
Pseudo-molecular ion (m/z 474.1554) and the experiment with β-glucuronidase indicated that O-glucuronide of C-1748 was formed in the presence of microsomal fractions. This reaction was selectively catalyzed by UGT2B7 and 2B17. High inhibitory effect of C-1748 was shown towards isoenzyme UGT1A9 (IC50 = 39.7 μM) and significant but low inhibitory potential was expressed in HT29 cell homogenate (IC50 = 84.5 μM). The mixed-type inhibition mechanism (Ki = 17.0 μM; Ki’ = 81.0 μM), induced by C-1748 was observed for recombinant UGT1A9 glucuronidation, whereas HT29 cell homogenate resulted in noncompetitive inhibition (Ki = 94.6 μM).Conclusions
The observed UGT-mediated metabolism of C-1748 and its ability to inhibit UGT activity should be considered as the potency for drug resistance and drug-drug interactions in the prospective multidrug therapy. 相似文献11.
Background
This study investigates the therapeutic potential of urothelin A in attenuating atherosclerotic lesion in wistar rat models and explore the role of Scavenger receptor-class B type I (SR-BI) and activation of Nrf-2 singling pathway.Methods
Wistar rats (n = 48) were feed with high cholesterol diet supplemented with Vitamin D3 and subjected to balloon injury of the aorta. Three days prior to the aortal injury, rats (n = 16) were administered urothelin A (3 mg/kg/d; po). Positive control were rats receiving high cholesterol diet and balloon injury of the aorta (n = 16). The sham group (n = 16) consisted of rats fed on basal diet. After twelve weeks blood was collected from all animals for estimation of lipid and angiotensin II (Ang II) levels along, subsequently all animals were sacrificed and morphologic analysis of the aorta was performed. Expression of SR-BI and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein were evaluated by Western blot.Results
After twelve weeks of treatment with urolithin A, there was a significant decrease in the plasma lipid and Ang II levels and improvement of aortic lesion compared with the sham group. There was an increased expression of SR-BI and inhibition of p-ERK1/2 (p < 0.05). The expression of SR-BI was inversely correlated with levels of Ang II.Conclusion
From the results it can be safely concluded that administration of urolithin A attenuates atherosclerosis via upregulation of SR-BI expression and inhibition of p-ERK1/2 levels. 相似文献12.
Aysu Hayriye Tezcan Omur Ozturk Sefer Ustebay Yasemen Adali Hatice Yagmurdur 《Pharmacological reports : PR》2018,70(2):340-345
Background
The aim of the present study was to determine the therapeutic effects of medical ozone therapy on acute acetaminophen (APAP)-induced hepatotoxicity which were not clearly demonstrated in prior studies.Method
Twenty-four mice were randomly assigned into three equal groups: Group 1 (control), Group 2 (APAP) and Group 3 (APAP +ozone). Hepatotoxicity was induced by APAP given as a single dose of 300 mg/kg intraperitoneally in Groups 2 and 3. Additionally, Group 3 received 20 mcg/0.5 mL ozone intraperitoneal twice a day for the remaining of the study. Other groups received saline injections. On the fourth day of the study, biochemical variables (AST, ALT, ALP) and liver histopathology was assessed.Results
Intraperitoneal administration of a single dose of APAP induced hepatocellular damage that was shown by both liver enzymes and histopathological changes (p < 0.001). AST, ALT, ALP levels were elevated in both groups 2 and 3 and the difference from group 1 was statistically significant (p < 0.01).Mean ALT and AST levels of group 2 were statistically significantly higher versus group 3 (p < 0.01). In histopathological examinations; necrosis and inflammation were more prominent in Group 2 compared to Group 3 (p < 0.01).Conclusion
Ozone showed beneficial effects on APAP hepatotoxicity at a statistically significant level. It is known that ozone has therapeutic effects in various diseases owing to its antioxidant effects. The present study suggests that ozone may be utilized as a routine supplementary therapy in acute APAP hepatotoxicity. 相似文献13.
JinHong Jiang WeiDong Jin YaLi Peng XueYa Liang Shu Li LiJuan Wei ZhiPing Lei LongFei Li Min Chang 《Pharmacological reports : PR》2018,70(2):355-363
Background
This study aimed to investigate the functional roles of Cortistatin-14 (CST-14) in the gastrointestinal (GI) motility.Methods
For in vivo study, mice were randomly divided into control, ip injected CST-14 (0.1, 0.5, 1, 5, 10 mg/kg) + control group, icv injected CST-14 (5 μg) + control group, dextran sulfate sodium-induced colitis group, CST-14 + colitis group, castor oil-induced diarrhea group, CST-14 + diarrhea group. We carried out these experiments by quantitative real-time PCR, GI transit, bead expulsion and fecal pellet output. For in vitro study, effects of CST-14 were investigated in the longitudinal and circular muscle contractions of jejum, ileum, and colon.Results
In vivo, the expression of CST-14 mRNA was significantly decreased in the colon of colitis mice and CST-14 significantly inhibited GI transit rate in colitis mice, and delayed the emergence of liquid feces in castor oil-induced diarrhea mouse model. Additionally, ip injection of CST-14, but not icv injected, remarkably inhibited GI transit, bead expulsion and fecal pellet output in mice. In vitro assays, CST-14 (10?6 M) could relax the rhythms of the longitudinal muscles and circular muscles of the jejunum, ileum and colon of mice. The further study indicated that the roles of CST-14 in mouse GI motility were significantly reversed by c-SOM (sstr1-5 antagonist), especially sstr2 and sstr3 and propranolol (β-adrenoceptor blocker), suggesting that somatostatin system and noradrenaline system were involved in the inhibiting effects of CST-14 in GI.Conclusion
Such inhibiting effects imply that CST-14 system in gastrointestinal motility might be a new target for treatment of GI tract disorder. 相似文献14.
Farzaneh Shakeri Nama Mohamadian Roshan Mahsa Kaveh Naeima Eftekhar Mohammad Hossein Boskabady 《Pharmacological reports : PR》2018,70(5):981-987
Background
Curcumin has shown various pharmacological effects such as anti-inflammatory activities. In this study, the effects of curcumin on tracheal responsiveness and lung pathological features were evaluated in a rat model of asthma.Methods
Tracheal responsiveness and lung pathological features were evaluated in control rats (C), ovalbumin (OVA)-sensitized rats (as an animal model of asthma; A), A rats treated with curcumin (Cu, 0.15, 0.30, and 0.60 mg/ml) and dexamethasone (D, 1.25 μg/ml), (n = 8 in curcumin-treated groups and n = 6 in other groups). Curcumin and dexamethasone were added to animals’ drinking water during the sensitization period.Results
Asthmatic group showed increased lung pathological score and tracheal responsiveness to methacholine and OVA compared to control group (p < 0.01 to p < 0.001). Pathological features including interstitial inflammation, interstitial fibrosis, bleeding, and emphysema as well as tracheal responsiveness to methacholine and OVA, were significantly decreased in treated groups with dexamethasone and all concentrations of curcumin compared to group A (p < 0.05 to p < 0.001). Epithelial damage was also significantly decreased in treated groups with the two higher concentrations of curcumin (p < 0.05 to p < 0.001).Conclusion
Curcumin showed preventive effects on tracheal responsiveness and lung pathological features in asthmatic rats. 相似文献15.
Sayed Aliul Hasan Abdi Mohd Amir Afjal Abul Kalam Najmi Sheikh Raisuddin 《Pharmacological reports : PR》2018,70(4):769-776
Background
The aim of this study was to evaluate the modulatory effect of S-allyl cysteine against cyclophosphamide-induced changes in uroplakin IIIa, CCL11 and TNF-α.Methods
Mice were treated with cyclophosphamide (200 mg/kg × 7 d, ip). S-allyl cysteine (150 mg/kg × 7d, ip), and comparator compound mesna (40 mg/kg × 7d, ip) were administered 1 h before and 4 h after each cyclophosphamide dose. The urinary bladder was analysed for mRNA and protein changes in uroplakin IIIa (UPIIIa), CCL11 and TNF-α and histopathological findings.Results
Cyclophosphamide caused hemorrhagic cystitis formation and downregulation of UPIIIa. These changes were accompanied by upregulation of CCL11 and TNF-α. S-allyl cysteine attenuated these changes including protection at histological level. Mesna which was used as a comparator drug also showed protection. However, relatively S-allyl cysteine showed a stronger protective effect than mesna.Conclusion
These findings highlight a correlation between downregulaion of UPIIIa and enhanced production of inflammatory biomarkers and protective effects of S-allyl cysteine which has been reported to be a potent uroprotective agent. The present study strengthens its role which could be clinically exploited in chemotherapy regimen. 相似文献16.
Background
The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats.Methods
STZ (3 mg/kg bilaterally) as intracerebroventrical (icv) route was administered on day 1 and 3 in rats. Donepezil (5 mg/kg/day po), used as standard, and BA (5, 10 and 15 mg/kg/day po) were administered after 1 h of 1st STZ infusion up to 21 days. Object recognition task (ORT) for non-spatial, Morris water maze (MWM) for spatial and locomotor activity were performed to evaluate behavioral changes in rats. On 22nd day, animals were decapitated and hippocampus was separated to perform biochemical (AChE, LPO, GSH, nitrite), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (NTs) (dopamine, norepinephrine and serotonin) analysis.Results
STZ infusion significantly impaired memory as observed in MWM and ORT, increased oxidative stress, pro-inflammatory cytokine’s level and altered NTs level. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA dose dependently (5, 10 and 15 mg/kg) significantly restore STZ induced memory changes and pathological abnormalities in rat brain.Conclusions
The findings of the current study suggests that BA protect rat brain from STZ induced neuronal damage via acting through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders especially AD. 相似文献17.
Grzegorz Grześk Wioleta Stolarek Michał Kasprzak Marek Krzyżanowski Katarzyna Szadujkis-Szadurska Michał Wiciński Elżbieta Grześk 《Pharmacological reports : PR》2018,70(1):184-189
Background
Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1–2 ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood.Methods
The presented research was based on a retrospective analysis including 2149 patients treated with digoxin and hospitalized between 1980 and 2000. Was used for the determination of SCD automatic analyzer TDX ABBOTT GmbH – fluorescence polarization immunoassay (FPIA), with therapeutic range for digoxin of 0.8–2.0 ng/ml.Results
Average SCD result in the study population was located within the therapeutic range and amounted 1.06 ng/ml (55.7% of patients). Statistically significant differences in digoxin level were observed depending on the way of medicine administration (p = 0.000001) and the daily amount (p = 0.001). Moreover, statistically significant differences in digoxin level were observed depending on sex (p = 0.00002).Conclusions
An elevated level of digoxin was observed in the case of patients who received the medication both orally and intravenously, together with an increase in the daily amount of digoxin doses. It was confirmed that an elevated digoxin level occurs in the course of treatment in the case of women. 相似文献18.
Hong-Bo Xiao Guo-Guang Sui Xiang-Yang Lu Zhi-Liang Sun 《Pharmacological reports : PR》2018,70(3):439-445
Background
Mastitis is inflammation of a breast (or udder). Angiopoietin-like protein 2 (ANGPTL2) has been found as a key inflammatory mediator in mastitis. Purpose of this research was to investigate the mechanisms about repressing effect of kaempferol on mastitis.Methods
Forty mice were randomly divided into 4 groups (n = 10): C57BL/6J control mice, untreated murine mastitis, 10 mg/kg kaempferol treated murine mastitis (ip), and 30 mg/kg kaempferol treated murine mastitis (ip). Primary cultured mouse mammary epithelial cells (MMEC) were indiscriminately divided into seven groups including control group, 10 mmol/L vehicle of kaempferol group, 10 μmol/L kaempferol treated group, 20 μg/mL LPS treated group, 1 μmol/L kaempferol plus LPS treated group, 3 μmol/L kaempferol plus LPS treated group, and 10 μmol/L kaempferol plus LPS treated group.Results
In murine mastitis, kaempferol (10 or 30 mg/kg) treatment prevented mastitis development, decreased myeloperoxidase (MPO) production, interleukin (IL)-6 level, tumour necrosis factor-α (TNF-α) concentration, and ANGPTL2 expression. In MMEC, kaempferol (1, 3 or 10 μM) reduced MPO production, TNF-α concentration, IL-6 level, and ANGPTL2 expression.Conclusions
The results in present study show that kaempferol modulates the expression of ANGPTL2 to lessen the mastitis in mice. 相似文献19.
Samah S. Abbas Hesham M. Mahmoud Mona F. Schaalan Hanan S. El-Abhar 《Pharmacological reports : PR》2018,70(4):720-729
Background
The current study is focusing on the role of brain natriuretic peptide (BNP), a substrate of dipeptidyl peptidase-4 (DPP-4) enzyme, and its signaling survival pathway in the cardioprotective mechanism of sitagliptin, a DPP-4 inhibitor.Methods
Male Wistar rats were randomized into 7 groups, sham, I/R, KT-5823 (selective protein kinase (PK) G inhibitor), 5-HD (selective mito-KATP channel blocker), sitagliptin (300 mg/kg, po), sitagliptin + KT-5823, and sitagliptin + 5-HD. Sitagliptin was administered for 3?days prior to induction of coronary I/R, while either KT-5823 or 5-HD was administered intravenously 5 min before coronary ligation.Results
Pretreatment with sitagliptin provided significant protection against I/R injury as manifested by decreasing, percentage of infarct size, suppressing the elevated ST segment, reducing the increased cardiac enzymes, as well as DPP-4 activity and elevating both heart rate (HR) and left ventricular developed pressure (LVDP). However, the addition of either blocker to sitagliptin regimen reversed partly its cardioprotective effects. Although I/R increased BNP content, it unexpectedly decreased that of cGMP; nevertheless, sitagliptin elevated both parameters, an effect that was not affected by the use of the two blockers. On the molecular level, sitagliptin decreased caspase-3 activity and downregulated the mRNA levels of BNP, Bax, and Cyp D, while upregulated that of Bcl2. The use of either KT-5823 or 5-HD with sitagliptin hindered its effect on the molecular markers tested.Conclusions
The results of the present study suggest that the cardioprotective effect of sitagliptin is mediated partly, but not solely, through the BNP/cGMP/PKG survival signaling pathway. 相似文献20.