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1.
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2.
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3.
Agnieszka Matuszewska Beata Nowak Diana Jędrzejuk Marcin Landwójtowicz Ewa Sadanowicz Tomasz Sozański Joanna Kwiatkowska Małgorzata Pieśniewska Marek Bolanowski Adam Szeląg 《Pharmacological reports : PR》2018,70(5):951-954
Background
Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones.Methods
The experiment was carried out on young male Wistar rats divided into two groups receiving either ranitidine (10 mg/kg ip) or vehicle.Results
A significant decrease in femoral BMD in ranitidine-treated rats (R) compared to vehicle-treated ones (C) was detected (0.262 ± 0.009 g/cm2vs. 0.271 ±0.007 g/cm2, p < 0.05). In group R we observed elevated serum C-terminated telopeptide of type I collagen (CTX) level with concomitantly lowered serum osteocalcin (OC) concentration comparing to control group (151.2 ± 27.2 pg/ml vs. 101.5 ± 55.6, p < 0.05 and 229.1 ± 50.0 pg/ml vs. 292.0 ± 52.9, p < 0.05, respectively). Serum concentration of inorganic phosphorus was lower in group R than in group C (134 ± 13 mmol/L vs. 157 ± 28 mmol/L, p < 0.05).Conclusions
Long-term administration of ranitidine increases bone resorption and decreases bone formation in growing rats leading to decrease in BMD. 相似文献4.
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5.
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6.
Archana Mahobiya Thakur Uttam Singh Soya Rungsung Tarun Kumar Gokul Chandrasekaran Subhashree Parida Dinesh Kumar 《Pharmacological reports : PR》2018,70(5):863-874
Background
Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms.Methods
Tension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab.Results
Kaempferol (10?8–10?4.5 M) caused concentration-dependent relaxation (Emax 124.33 ± 4.37%; pD2 5.03 ± 0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (Emax 55.53 ± 7.72%) in 60 mM K+ pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (Emax 71.68 ± 11.84%) the relaxation response. However, glibenclamide, BaCl2, 4-AP (1 mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10 mM) and 4-AP (5 mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (Emax 94.92 ± 19.60%) in presence of ODQ. H89 significantly decreased (Emax, 98.38 ± 8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K+ (80 mM)-depolarized arterial rings, kaempferol (10 μM) markedly reduced CaCl2-induced contractions (Emax 35.14 ± 6.53% vs. control 69.04 ± 15.19%).Conclusion
Kaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BKCa channel, sGC, PKA pathways and inhibition of Ca2+-influx through L-type calcium channels. 相似文献7.
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8.
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.
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.
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13.
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14.
José Luis Cortes-Altamirano Samuel Reyes-Long Adriana Olmos-Hernández Herlinda Bonilla-Jaime Paul Carrillo-Mora Cindy Bandala Alfonso Alfaro-Rodriguez 《Pharmacological reports : PR》2018,70(2):385-389
Background
Levetiracetam (LEV) is a novel anticonvulsant with proven antinociceptive properties. However, the antinociceptive and pronociceptive effect of this drug has not yet been fully elucidated in a tonic pain model.Methods
Thirty-six male rats (Wistar) were randomized into six groups and underwent the formalin test as follows: rats in the control group were administered 50 μL of 1% formalin in the paw; sham-group rats were administered 50 μL of saline in the paw to mimick the application of formalin; the four experimental groups were administered LEV intragastrically (ig) (50, 100, 200 and 300 mg/kg), and 40 min later 50 μL of 1% formalin was injected in the paw.Results
LEV exhibited antinociceptive effect in the 300 mg/kg LEV group (p < 0.05) and a pronociceptive effect in the 100 mg/kg LEV group (p < 0.05) and in the 50 mg/kg LEV group (p < 0.001).Conclusions
The antinociceptive and pronociceptive effect of LEV in a tonic pain model is dose-dependent. 相似文献15.
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16.
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17.
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18.
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19.
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20.