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1.
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2.
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3.
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4.
Protective effects of curcumin on acrolein-induced neurotoxicity in HT22 mouse hippocampal cells 总被引：1，自引：0，他引：1
Lan-Ying Shi Li Zhang Hui Li Tao-Li Liu Ji-Cai Lai Zhi-Bing Wu Jian Qin 《Pharmacological reports : PR》2018,70(5):1040-1046
Background
Aging is one of the most important inevitable risk factors of Alzheimer disease (AD). Oxidative stress plays a critical role in the process of aging. Curcumin has been proposed to improve neural damage, especially neurodegenerative injury, through its antioxidant and anti-inflammatory properties. Therefore, we investigated the effects of curcumin on acrolein-induced AD-like pathologies in HT22 cells.Methods
HT22 murine hippocampal neuronal cells were treated with 25 μM acrolein for 24 h with or without pre-treating with curcumin at the selected optimum concentration (5 μg/mL) for 30 min. Cell viability and apoptosis were measured by CCK8 assay and flow cytometric analysis. Levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected by a GSH assay kit or commercial assay kits, respectively. Alterations in the expression of BDNF/TrkB and key enzymes involved in amyloid precursor protein (APP) metabolism were assessed by western blotting.Results
Data showed that curcumin significantly reversed acrolein-induced oxidative stress indicated by depletion of GSH and SOD, and elevation of MDA. The findings also suggested curcumin’s potential in protecting HT22 cells against acrolein through regulating the BDNF/TrkB signaling. In addition, acrolein-induced reduction in A-disintegrin and metalloprotease, and the increase of amyloid precursor protein, β-secretase, and receptor for advanced glycation end products were reversed either, and most of them were nearly restored to the control levels by curcumin.Conclusion
These findings demonstrate the protective effects of curcumin on acrolein-induced neurotoxicity in vitro, which further suggests its potential role in the treatment of AD. 相似文献5.
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6.
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7.
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8.
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9.
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10.
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11.
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12.
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13.
Background
Candesartan is one of the standard antihypertensive drug belonging to AT1R angiotensin receptor blockers (ARBs) group. Beneficial effects of this drug in the treatment of hypertension are well recognized. In this study we tested a hypothesis that candesartan could alleviate age-related memory decline.Methods
Aged and young rats have been treated with candesartan (0.1 mg kg?1) for 21 days and then underwent a battery of behavioral tests: for assessment of long-term memory (Passive avoidance test – PA), recognition memory (Object recognition test – OR), locomotor functions (Open field – OF) and anxiety behavior (Elevated plus maze – EPM).Results
Aged rats (2-years-old) displayed clear declining tendency in the retrieval of passive avoidance behavior showing thus increased forgetting. Prolonged administration of candesartan significantly (p < 0.01) reversed this phenomenon causing recall measured as the avoidance latency, and surprisingly also showed the tendency to recall deterioration observed in the young rats. More optimistic results were achieved in the OR, where candesartan significantly improved recognition memory (p < 0.001) of aged rats who performed even better than the young ones (p < 0.05).Conclusions
It appears that candesartan potently abolishes some kinds of aging-induced memory impairments and cognitive declines in aged rats, but in some circumstances it may even could increase the damage of memory. It seems that the use of sartans in the treatment of hypertension for patients with associated cognitive impairment, or for people in risk groups for such disorders can be an interesting alternative. 相似文献14.
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15.
Hanaa Mahmoud Ali 《Pharmacological reports : PR》2018,70(4):804-811
Background
Lead acetate (Led) and mercury chloride (Mer) represent important ecological and public health concerns due to their hazardous toxicities. Naturally found products play a vital role in chemopreventive agent innovation. The current study aimed to assess the modifying effect of garlic (Gar) and/or vitamin E (Vit E) against the half-maximal inhibitory concentration (IC50) Led and/or Mer-induced cytotoxic, genotoxic and apoptotic effects.Methods
Human lung cells (WI-38) were pretreated with Gar and/or Vit E for 24 h and then treated with Led and/or Mer either alone or with their combination for 24 h. Cytotoxicity of Led and Mer and the viability of Gar and Vit E were assessed using MTT assay. The alkaline comet assay was used to assess DNA damage, whereas QRT-PCR was performed to evaluate p53, Bax, and Bcl2 mRNA-expression.Results
The results of this study showed that IC50 of Led was (732.72 μg/mL) and for Mer was (885.83 μg/mL), while cell viability effective dose for Gar was (300 μg/mL) and for Vit E was (26,800 μg/mL). Treating cells with the IC50-concentration of Led or Mer or their combination using half IC50 of both of them induced severe DNA-damage. Bax-expression was increased, while p53 and Bcl2-expressions were decreased. Pretreatment of cells with Gar and/or Vit E ameliorated the previous alternations.Conclusions
Led and Mer can induce oxidative stress and change the expressions of apoptosis-related proteins in WI-38 cells. Gar and Vit E may be promising protective candidate agent against the toxic effect of heavy metals. 相似文献16.
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17.
Marwa Ahmed Amin Atallah Samah M. Elaidy Mona K. Tawfik 《Pharmacological reports : PR》2018,70(3):509-518
Background
In liver fibrosis, a major morbid and mortal disease, oxidative stress motivation of hepatic stellate cells (HSCs)-into myofibroblasts terminated in collagen deposition remain the key pathophysiological deal. Serotonin (5-HT) through its HSCs-expressed receptors, especially 5-HT2A and 7, shows crucial events in fibrogenesis of chronic liver diseases. Molecular hepatic oxidative stress-fibrotic roles of 5-HT2A and 7 receptors antagonists (ketanserin and SB-269970 respectively) are still a challenging issue.Methods
Seven groups of adult male Wistar rats (n = 10) were used. A carbon tetrachloride (CCl4) solution was injected intraperitoneally twice weekly for 6 weeks. On the 7th week, rats developed liver fibrosis were treated either by ketanserin (1 mg/kg/day, ip) or SB-269970 (2 mg/kg/day, ip) for 14 days. Survival rates, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in addition to hepatic malondialdehyde (MDA) and reduced glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and transforming growth factor-beta1 (TGF-β1) and procollagen type I N-terminal propeptide (PINP) levels, beside the hepatic histopathological fibrotic changes, were evaluated.Results
In CCl4-challenged rats, each therapeutic approach showed significant reductions in elevated serum ALT, and AST levels, hepatic MDA, TGF-β1, and PINP levels, and histopathological hepatic fibrotic scores as well as significant elevations in survival rates, reduced hepatic GSH levels, and SOD, and CAT activities. Remarkably, significant ameliorative measurements were observed in SB-269970 treated group.Conclusion
Blockade of 5-HT2A and 7 receptors each alone could be a future reliable therapeutic approach in liver fibrosis through a reduction in oxidative stress/TGF-β1-induced HSCs activation pathway. 相似文献18.
Rowaida Refaat Dalia Sarhan Metwali Kotb Eman El-Abd Emad El-Bassiouni 《Pharmacological reports : PR》2018,70(2):304-308
Background
The present study aimed to investigate the possible post-irradiation protective effects of ectoine on CNS and testes of male mice.Methods
The study included thirty male Swiss albino mice (20–22 gm). Mice were divided into five groups (six each); controls (injected intraperitoneally with 0.2 ml saline), irradiated group 1 (received six Gy whole body x-irradiation single dose, injected with saline, and sacrificed after one day), irradiated group 2 (x-irradiated, injected with saline, and sacrificed after one week), ectoine group 1 (x-irradiated, injected with 200 mg/kg ectoine, and sacrificed after one day), and ectoine group 2 (x-irradiated, injected daily with 200 mg/kg ectoine, and sacrificed after one week). IL-1β, IL-6, IL-10, PGE2, MDA, GSH, GSSG, and GSH/GSSG ratio were evaluated in CNS and testes.Results
IL-1β, IL-6, IL-10, PGE2, and MDA are significantly elevated in the CNS and testes of x-irradiated groups when compared with controls. IL-1β, IL-6, IL-10, and PGE2 significantly elevated at one week than one day while MDA significantly decreased. A significant decrease in the concentration of GSH and in the GSH/GSSG ratios coupled with an opposite effect on GSSG was noted. Ectoine treatment significantly ameliorated the biochemical effects induced by whole body x-irradiation. All the tested parameters tended to go back to near control values. It was noted that the modulating action was dependent on the accumulation of ectoine as it was more effective after repeated administration.Conclusion
Ectoine has post-irradiation protective effects on CNS and testes via its action on inflammatory and oxidative stress pathways. 相似文献19.
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20.
Enrique Gallego-Colon Agnieszka Klych-Ratuszny Agnieszka Kosowska Wojciech Garczorz Mohammad Reza F. Aghdam Michal Wozniak Tomasz Francuz 《Pharmacological reports : PR》2018,70(1):178-183