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1.
Background
Even after several novel therapeutic approaches, the number of people with diabetic nephropathy (DN) still continues to increase globally, this suggest to find novel therapeutic strategies to prevent it completely. Recent reports, are indicating the ubiquitin proteasome system alterations in DN. Recently, we also showed that, histone H2AK119 mono-ubiquitination (H2AK119-Ub) found to regulate Set7, a key epigenetic enzyme in the development of renal fibrosis under type 1 diabetic condition. Hence, we aimed to study the role of a known 20 s proteasome inhibitor Aspirin, on histone ubiquitination in the progression of DN.Methods
Male Wistar rats were rendered diabetic using a single dose of Streptozotocin (55 mg kg?1, ip). After 4 weeks, diabetic animals were grouped into respective groups and the drug, aspirin, low dose (25 mg kg?1 day?1), high dose (50 mg kg?1 day?1) was administered through po route. At the end of the study, kidneys from all the groups were collected and processed separately for glomerular isolation, protein isolation, and for histopathological studies.Results
Aspirin administration, reduced the protein expression of Mysm1, increased the protein expression of H2AK119-Ub and thereby reduced the Set7 protein expression in glomeruli isolated from diabetic animals and prevented renal fibrosis.Conclusions
In conclusion, our results are clearly indicating that, aspirin prevents renal fibrosis in diabetic animals through decreasing the expression of Mysm1, increasing the expression of H2AK119-Ub and thereby decreasing the protein expression of Set7, which is a novel mechanism. Moreover, this mechanism may lay down a novel strategy to prevent DN completely in future. 相似文献2.
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3.
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4.
Felipe J. Cavichioli Graylin N.B. Bernal Iandra Holzmann Juliana Bagatini Klein Ricardo Escarcena Esther Del Olmo Arturo San Feliciano Valdir Cechinel Filho Nara L.M. Quintão 《Pharmacological reports : PR》2018,70(4):753-759
Background
The study evaluated the effects of two sphingosine derivatives N-(2-tert-butoxycarbamylhexadecyl)glutaramide (AA) and N-(1-benzyloxyhexadec-2-yl)glutaramide (OA) in different models of hypersensitivity in mice.Methods
Male Swiss mice were orally pre-treated with AA or OA (0.3–3 mg/kg). After 1 h, they received λ-carrageenan (300 μg/paw), lipopolysaccharide (LPS; 100 ng/paw), bradykinin (BK; 500 ng/paw) or prostaglandin E2 (PGE2; 0.1 nmol/paw) or epinephrine (100 ng/paw), and the mechanical withdrawal thresholds were evaluated using von Frey filament (0.6 g) at different time points. The effect of the compounds against inflammatory and neuropathic pain was also evaluated using complete Freund’s adjuvant (CFA), or by performing partial sciatic nerve ligation (PSNL).Results
Animals pre-treated with AA and OA reduced hypersensitivity induced by carrageenan, LPS and BK, and modest inhibition of PGE2-induced hypersensitivity and carrageenan-induced paw oedema were observed in mice treated with OA. Though the partial effect presented by AA and OA, when dosed once a day, both compounds were able to significantly reduce the persistent inflammatory and neuropathic pain induced by CFA and PSNL, respectively.Conclusion
These results demonstrate that the sphingosine derivatives AA and OA present important anti-hypersensitive effects, suggesting a possible interaction with the kinin signalling pathway. This may represent an interesting tool for the management of acute and chronic pain, with good bioavailability and safety. 相似文献5.
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6.
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7.
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8.
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9.
Background
Previous clinical and preclinical studies have indicated that the N-methyl-d-aspartate (NMDA) receptor antagonist, memantine, has neuroprotective properties as well as antidepressant effects. The present study was designed to examine behavioral and molecular effects of memantine administration in rats subjected to the repeated unpredictable stress (RUS) paradigm.Methods
Rats were split into four groups at random including control + saline, control + memantine, stressed + saline and stressed + memantine. After 10 days of exposure to the RUS paradigm, rats were administered memantine (20 mg/kg) intraperitoneally (ip) for 14 days. Depression-like behavior and memory performance were assessed by measuring immobility time in the forced swim test and passive avoidance test, respectively. The mRNA levels of BDNF and TrkB in the prefrontal cortex and hippocampus were measured by real-time quantitative PCR.Results
Our results demonstrated that the RUS paradigm caused depression-like behavior and impairment of memory retrieval in rats. We did not find significant changes in BDNF or TrkB mRNA levels in hippocampus, but mRNA levels of TrkB in the prefrontal cortex showed a significant downregulation. Administration of memantine reversed depression-like behavior and memory impairment and significantly increased BDNF and TrkB mRNA levels in both prefrontal cortex and hippocampus of stress exposed rats.Conclusions
Our study supports the hypothesis that drugs with antagonistic properties on the NMDA receptor, such as memantine, might be efficient in treatment of major depression. Our results also suggest that upregulated mRNA levels of BDNF and TrkB in the brain might be essential for antidepressant-like activity of memantine in stress exposed rats. 相似文献10.
Nastaran Rahimi Mahsa Hassanipour Narges Sistany Allahabadi Fatemeh Sabbaghziarani Maryam Yazdanparast Ahmadreza Dehpour 《Pharmacological reports : PR》2018,70(3):426-433
Background
Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats.Methods
Colitis was induced by acetic acid 28 days after bile duct ligation (BDL). L-NAME, as an inhibitor of NO synthase and naltrexone, as an antagonist of opioid receptors were administered intraperitoneally to animals during 3 days after induction of colitis. Macroscopic colitis lesion area, inflammatory mediators change, NO metabolite levels, and colon microscopic injuries were assessed 3 days after induction.Results
Cirrhosis significantly reduced the severity of damages to the colon. Administration of L-NAME (10 mg/kg), naltrexone (10 mg/kg) and co-administration of L-NAME (1 mg/kg) and naltrexone (5 mg/kg) significantly decreased the protective effect of BDL on colitis. Nitrite elevated levels in BDL rats were significantly diminished in L-NAME- and naltrexone-treated animals. Histopathology parameters and cytokines level alterations in the colon of acetic acid-treated animals after BDL was reversed after injection of L-NAME, naltrexone, and co-administration of L-NAME (1 mg/kg) + naltrexone (5 mg/kg).Conclusion
Cirrhosis improved the intestinal damages induced by acetic acid in rats which may be mediated through interaction of nitrergic and opioidergic systems. 相似文献11.
Background
Currently available antiepileptic drugs offer limited symptomatic treatment and fail to cure more than 30% of the epileptic seizures. (Arylalkyl)azoles are a class of anticonvulsants including nafimidone and loreclezole. Here, we report the design and synthesis of new (arylalkyl)azoles in N-[1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethylidene]hydroxylamine ester structure, their anticonvulsant screening and in silico prediction studies of their pharmacokinetic properties.Methods
The title compounds were synthesized according to the Steglich esterification of N-[1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethylidene]hydroxylamine with various carboxylic acids. Anticonvulsant identification and quantification tests were performed in mice by the Epilepsy Therapy Screening Program (ETSP) of the National Institutes of Health (NIH) using 6 Hz psychomotor, maximal electroshock (MES), and rotorod tests. Their physicochemical and pharmacokinetic properties were calculated using QikProp.Results
Most of the compounds showed protection against 6 Hz- and/or MES-induced seizures. 4a, 4b, and 4 g were active at 100 mg/kg, 4 g was active in both tests without neurotoxicity. According to the QikProp calculations the title compounds were druglike and had some favourable properties such as high membrane permeability and oral absorptivity.Conclusion
Anticonvulsant screening of a set N-[1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethylidene]hydroxylamine esters yielded some active derivatives in 6 Hz and MES test. Especially, 4 g emerged as a promising compound with activity at 100 mg/kg and no toxicity. The compounds were predicted to be drug like and have good pharmacokinetic properties except hERG inhibition, which needs to be addressed in further optimization studies. 相似文献12.
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13.
Background
Well known risk factors for diabetic erectile dysfunction include impaired nitric oxide synthesis and endothelial dysfunction. We proposed to evaluate the efficacy of nitric oxide donor, molsidomine in rat model of diabetic erectile dysfunction.Methods
Streptozotocin (52 mg/kg, ip) induced diabetic male rats were treated with molsidomine (5 and 10 mg/kg, po) for 8 weeks. The sexual behaviour of male rat in presence of the female rat in oestrous phase was observed at the end of study. The effect of treatment on serum testosterone level, sperm parameters and penile tissue histopathology was also evaluated. Further anti-inflammatory activity and antioxidant potential of molsidomine was evaluated by in vitro method. In silico docking study was carried out to appreciate binding conformation of the molsidomine to its plausible target, phosphodiesterase enzyme.Results
Molsidomine significantly and dose dependently increased sexual behaviour, sperm count and serum testosterone level in diabetic rats. Further, the protective effect of molsidomine was also substantiated by pathological changes in the architect of the penile tissue. Molsidomine showed good membrane stability accounting for its significant anti-inflammatory action and also significantly scavenged DPPH radical activity showing its antioxidant action. Molsidomine was found to settle well in the active site of PDE-5 enzyme with less binding affinity than the standard drug sildenafil.Conclusion
The results highlight the rationale behind the repositioning of molsidomine therapy for the management of diabetic erectile dysfunction. 相似文献14.
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.
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18.
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19.
Małgorzata Olszewska-Banaszczyk Paulina Jackowska Paulina Gorzelak-Pabiś Edyta Pytel Maria Koter-Michalak Marlena Broncel 《Pharmacological reports : PR》2018,70(2):258-262
Background
Abnormalities in the physical properties of the red blood cells (RBCs) membranes may underlie the defects that are strongly linked to cardiovascular diseases (CVD).The aim of the study was to compare the effects of two therapies of equal hipolipemic efficacy on the erythrocyte membrane fluidity, concentration of membrane cholesterol, lipids peroxidation and RBCs distribution witdh in patients with CVD.Methods
The study included 44 patients with angiographic evidence of CVD, who despite previous 6-month hypolipemic therapy, did not achieve the concentration of LDL-C <70 mg/dl. They were randomly assigned to: rosuvastatin 20 mg/day (R20) and atorvastatin 10 mg/day combined with ezetimibe 10 mg/day (A10 + E10). The membrane fluidity, the concentration of thiobarbituric acid reactive substances ?TBARS, concentration of membrane cholesterol were evaluated after 6 months therapy.Results
An improvement in lipid parameters was observed in each of the groups studied. In R20 the treatment resulted in 33% reduction concentrations of TBARS in serum, as well as in a decrease in membrane cholesterol by 16%, fluorescence anisotropy of TMA-DPH by 17.7%, fluorescence anisotropy of DPH by 2.8%. In A10 + E10 the reduction of TBARS by 20.5% in serum, membrane cholesterol by 15.8% as well as a 14.25% increase in RBC membrane fluidity in the superficial layer (TMA-DPH) and decrease fluidity in the deep layer (DPH) were observed.Conclusion
Rosuvastatin increases the fluidity of erythrocyte membrane and decreases the TBARS in serum to greater extent than does equal hipolipemic combined therapy atorvastatin with ezetimibe. 相似文献20.
Clarissa Vasconcelos de Oliveira Viviane Nogueira Zorzi Michele Rechia Fighera Luiz Fernando Freire Royes Ana Flávia Furian Mauro Schneider Oliveira 《Pharmacological reports : PR》2018,70(2):364-371