共查询到20条相似文献，搜索用时 31 毫秒
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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3.
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
Background
The process by which a brain insult elicits epilepsy is termed epileptogenesis and it is characterized by numerous molecular and functional alterations. Statins are first-line drugs for hypercholesterolemia and related diseases, and display neuroprotective properties in clinical and experimental studies. Considering the importance in developing therapeutic strategies to prevent or modify epileptogenesis, we aimed the present study to test the hypothesis that atorvastatin modifies seizure susceptibility of mice after status epilepticus (SE).Methods
Male and female C57BL/6 mice were submitted to the pilocarpine-induced SE and then treated with atorvastatin (10 or 100 mg/kg, once daily by gavage) for 14 days. At days 7 and 14 post SE we evaluated the susceptibility of mice to the convulsant effects of a low dose of PTZ (30 mg/kg). Cell loss in the hilus of dentate gyrus was evaluated by Giemsa staining.Results
Latencies to myoclonic jerks and to tonic-clonic seizures decreased between baseline (before SE) and days 7 and 14 after SE, confirming the development of seizure susceptibility. Atorvastatin protected against PTZ-induced tonic-clonic seizures in both sexes at day 14 post-SE. Protective effects were similar in both female and male mice, except that a high dose of atorvastatin was required for females (protection at 100 mg/kg versus 10 mg/kg in males). Giemsa staining did not reveal neuroprotective effects of atorvastatin.Conclusions
Atorvastatin treatment during epileptogenesis had slight beneficial effects on seizure susceptibility. These seem not related to neuroprotection. Further studies are needed to determine the disease-modifying potential of atorvastatin in epilepsy. 相似文献4.
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5.
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6.
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7.
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8.
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9.
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10.
Sattar Ostadhadi Saeed Shakiba Abbas Norouzi-Javidan Vahid Nikoui Samira Zolfaghari Mohsen Chamanara Ahmad-Reza Dehpour 《Pharmacological reports : PR》2018,70(5):1015-1022
Background
Considering the pivotal role of nitric oxide (NO) pathway in depressive disorders, the aim of the present study was to investigate the antidepressant-like effect of selegiline in mice forced swimming test (FST), and possible involvement of NO-cyclic guanosine monophosphate (cGMP) pathway in this action.Methods
After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4 min was evaluated. All drugs were given intraperitoneally (ip).Results
Selegiline (10 mg/kg) decreased the immobility time in the FST similar to fluoxetine (20 mg/kg). Pretreatment with l-arginine (NO precursor, 750 mg/kg) or sildenafil (a phosphodiesterase 5 inhibitor, 5 mg/kg) significantly reversed the selegiline anti-immobility effect. Sub-effective dose of selegiline (1 mg/kg) showed a synergistic antidepressant effect with NG-nitro-l-arginine methyl ester (L-NAME, inhibitor of NO synthase, 10 mg/kg) or 7-nitroindazole (specific neuronal NO synthase inhibitor, 30 mg/kg), but not with aminoguanidine (specific inducible NO synthase inhibitor, 50 mg/kg). Pretreatment of mice with methylene blue (an inhibitor of NO synthase and soluble guanylyl cyclase, 10 mg/kg) significantly produced a synergistic response with the sub-effective dose of selegiline. Neither of the drugs changed the locomotor activity. Also, hippocampal and prefrontal cortex (PFC) nitrite content was significantly lower in selegiline-injected mice compared to saline-administrated mice. Also, co-injection of 7-nitroindazole with selegiline produced a significant reduction in hippocampal or PFC nitrite contents.Conclusions
It is concluded that selegiline possesses antidepressant-like effect in mice FST through inhibition of l-arginine-NO-cyclic guanosine monophosphate pathway. 相似文献11.
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12.
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13.
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14.
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.
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.
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19.
Mostafa Mahmoud Hamdy Mohamed Mostafa Elbadr Ahmed Barakat 《Pharmacological reports : PR》2018,70(5):955-962
Background
Morphine – the main pillar of nociceptive pain management – systemic use is associated with development of tolerance and dependence. Tolerance and dependence lay a heavy burden in clinical pain management settings. An added weight to this dilemma is that effective, safe, and tolerable solution to this problem is still beyond reach. Antidepressants were reported as possible alleviators of opioid tolerance and dependence. One of the increasingly used antidepressant in clinical practice is bupropion given its high safety and tolerability profile.Methods
The study was performed on male Balb-c mice weighing 20–30 g. Hot plate test was used for assessment of bupropion (5 mg/kg, ip) possible analgesic activity and enhancement of morphine acute analgesia (1 and 5 mg/kg, sc). Repeated morphine (5 mg/kg, sc) administration for 9 days developed tolerance and dependence, bupropion (5 mg/kg, ip) was concurrently administered to evaluate its potential to modulate these processes. We also biochemically analyzed bupropion effect on these phenomena through modulation of neurotransmitters (glutamate and norepinephrine), inflammatory status (nitric oxide), and pro-antioxidant balance (malondialdehyde and reduced glutathione).Results
Bupropion was devoid of intrinsic analgesic activity and did not enhance morphine acute analgesia. However, bupropion significantly attenuated morphine tolerance and dependence development and abstinence syndrome with corresponding suppression of morphine induced changes in glutamate, norepinephrine, inflammatory status, and prooxidant-antioxidant balance.Conclusion
Bupropion efficacy in attenuation of morphine tolerance and dependence with its high safety and tolerability profile provide an alternative option to conventional agents e.g., ketamine and clonidine to modulate these phenomena. 相似文献20.
Saeed Mehrzadi Iman Fatemi Ali Reza Malayeri Ali Khodadadi Fatemeh Mohammadi Esrafil Mansouri Mohammad Rashno Mehdi Goudarzi 《Pharmacological reports : PR》2018,70(4):712-719