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1.
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2.
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3.
Jan Jaracz Edyta Tetera- Rudnicka Magdalena Bierejszyk Kaja Witczyk Agnieszka Raczyńska Wojciech Nowak Anna Pisarczyk Krzysztof Woźniak Wojciech Czernaś Adam Moniakowski Krystyna Jaracz 《Pharmacological reports : PR》2018,70(4):694-698
Background
The concomitant use of two or more mood stabilisers (MS), second-generation antipsychotics (SGA), lamotrigine as well as antidepressants, is frequently reported in the treatment of bipolar patients The aim of this study was to investigate the pattern of pharmacological treatment with special regard to polypharmacy defined as two or more psychiatric drugs taken at the same time in the same patients with bipolar disorder discharged from psychiatric units in Poland.Method
Pharmacotherapy of 127 consecutive patients (57 females and 70 males) with an ICD-10 diagnosis of bipolar disorder (BP) at the point of discharge from five psychiatric regional hospitals/units in Poland, was evaluated in 2015/2016 on the basis of medical files. The effect of treatment on mental status at discharge was examined using the Clinical Global Impression-Improvement scale (CGI-I).Results
When only MS, SGA and lamotrigine, were taken into account, 78 (61%) of patients were prescribed two, 27 (21.3%) three and one patient four medications. The combination of MS and SGA was most commonly used (n = 61, 48%). Medications preferred by Polish psychiatrists at patients’ discharge were valproates (n = 69, 54%), olanzapine (n = 48, 37%), quetiapine (n = 47, 37%) and lamotrigine (n = 33, 25.9%). Thirty patients (23.6%) were prescribed lithium. No relationships were found between polypharmacy and patients’ age, duration of illness and the rate of CGI-I. However, polypharmacy was significantly associated with types of bipolar disorder, particularly with the bipolar I disorder.Conclusion
The prevalence of polypharmacy especially with MS and SGA in the treatment of bipolar patients discharged from psychiatric units in Poland is high. The most significant factor predisposing to polypharmacy is a diagnosis of bipolar – I disorder. In general, our study confirms trends observed in other countries. 相似文献4.
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5.
Background
Vitamin D preparations reduce titers of thyroid antibodies in women with autoimmune thyroiditis. The same effect was induced by high-dose, but not moderate-dose-, statin therapy. No previous study has investigated the impact of concomitant treatment with a statin and vitamin D on thyroid autoimmunity.Methods
The study included three matched groups of women with Hashimoto’s thyroiditis and low vitamin D status. Groups B (n = 19) and C (n = 20) were treated with vitamin D (2000 IU daily). Because of coexistent hypercholesterolemia, groups A (n = 18) and B received simvastatin (40 mg daily). Plasma lipids, serum levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later.Results
At baseline, 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. In groups A and B, simvastatin reduced plasma levels of total and LDL cholesterol. Simvastatin produced no effect on thyroid antibody titers. Vitamin D decreased titers of thyroid peroxidase antibodies, as well as tended to decrease titers of thyroglobulin antibodies. Simvastatin-vitamin D combination therapy reduced serum titers of thyroid peroxidase and thyroglobulin antibodies and this effect was stronger than the effect of simvastatin and vitamin D administered alone. Treatment-induced changes in thyroid antibody titers correlated with baseline antibody titers, baseline levels of 25-hydroxyvitamin and treatment-induced changes in 25-hydroxyvitamin.Conclusions
The obtained results indicate that simvastatin may potentiate the impact of vitamin D on thyroid autoimmunity in vitamin D-deficient women with Hashimoto’s thyroiditis. 相似文献6.
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.
Faisal Imam Naif O. Al-Harbi Mohammad Matar Al-Harbi Mushtaq Ahmad Ansari Abdullah F Al-Asmari Mohd Nazam Ansari Wael A. Al-Anazi Saleh Bahashwan Mashal M Almutairi Musaad Alshammari Mohammad Rashid Khan Abdulaziz Mohammed Alsaad Moureq Rashed Alotaibi 《Pharmacological reports : PR》2018,70(5):993-1000
Background
Doxorubicin is an effective, potent and commonly used anthracycline-related anticancer drug; however, cardiotoxicity compromises its therapeutic potential. Apremilast, a novel phosphodiesterase type 4-inhibitor, reported to have anti-inflammatory effects and modulating many inflammatory mediators.Methods
The present study investigated the influence of apremilast against doxorubicin-induced cardiotoxicity in male Wistar rats. A total, 24 animals were divided into four groups of six animal each. Group 1, served as control and received normal saline. Group 2 animals, received doxorubicin (20 mg kg?1, ip). Group 3 and 4, treatment group, received doxorubicin (20 mg kg?1, ip) with the same schedule as group-2, plus apremilast (10 and 20 mg kg?1 day?1, po) respectively. Oxidative stress, caspase-3 enzyme activity, gene expression and protein expression were tested.Results
The results of the present study demonstrated that administration of apremilast reversed doxorubicin-induced cardiotoxicity.Conclusion
These findings suggested that apremilast can attenuate doxorubicin-induced cardiotoxicity via inhibition of oxidative stress mediated activation of nuclear factor-kappa B signaling pathways. 相似文献9.
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.
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11.
12.
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13.
Background
Accumulated evidence suggests that the enhanced brain angiotensin II (Ang II) activity is associated with stress and anxiety.More recent reports demonstrated that Ang II function is elevated in depression, but the role of hippocampal Ang II and its receptors in this state is not well established. The present study investigated the effects of Ang II and losartan (a selective Аng II type 1 receptor antagonist) microinjected into the hippocampal CA1 area on the anxiety-like behavior in rats with a model of depression.Methods
The bilateral olfactory bulbectomy (OBX) was used as a model of depression. The stereotaxic technique was used for bilaterally (right and left) implantation of guide cannulas into CA1 hippocampal area of the OBX rats. The anxiety state of OBX rats was studied using the elevated plus-maze test.Results
Тhe bilateral infusion of Ang II (0.5 μg) did not change the anxiety-like behavior of OBX rats, while losartan (100 μg) showed an anxiolytic-like behavior, by increasing the number and time of open arms entries, the ratio of open/total entries and open/total time and decreasing the number and time of closed arm entries.Conclusions
These findings demonstrated that the inhibition of hippocampal AT1 receptors reduces the anxiety in OBX rats, which indicates involvement of AT1 receptors in the mechanisms of OBX-induced anxiety. 相似文献14.
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15.
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16.
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17.
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18.
Background
To evaluate the protective effect of nebivolol against kidney damage and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat model.Methods
2K1C rats were obtained by clipping left renal artery of male Wistar rats and were considered hypertensive when systolic blood pressure (SBP) was ≥160 mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into untreated, nebivolol (10 mg/kg, ig), and atenolol (80 mg/kg, ig) treatment groups. The treatments lasted for 8 weeks. SBP, kidney structure and function, plasma and kidney angiotensin (Ang) II, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and the oxidant status were examined. Kidney protein expression of NADPH oxidase (Nox) isoforms and its subunit p22phox, nitric oxide synthase (NOS) isoforms, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 was tested by western blotting.Results
Nebivolol and atenolol exerted similar hypotensive effects. However, atenolol had little effect while nebivolol significantly ameliorated the functional decline and structural damage in the kidney, especially in non-clipped kidney (NCK), which was associated with the reduction of Ang II in NCK. Moreover, nebivolol inhibited the NCK production of reactive oxygen species (ROS) by decreasing Nox2, Nox4, and p22phox expression. Further, nebivolol reduced the plasma and kidney ADMA levels by increasing DDAH2 expression and decreasing PRMT1 expression. Nebivolol also increased the NCK NO level by ameliorating the expression of kidney NOS isoforms.Conclusions
Our results demonstrated that long-term treatment with nebivolol had renoprotective effect in 2K1C rats partly via regulation of kidney ROS-ADMA-NO pathway. 相似文献19.
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20.
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