Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Analysis of very important pharmacogene variants in the Tibetan population from China.","authors":"Hao Rong,&nbsp;Hongzhi Dong,&nbsp;Xue He,&nbsp;Dongya Yuan,&nbsp;Mei Bai,&nbsp;Li Wang,&nbsp;Tao Liu,&nbsp;Yongjun He,&nbsp;Jianwen Zheng,&nbsp;Yuhe Wang,&nbsp;Tianbo Jin","doi":"10.1111/1440-1681.13327","DOIUrl":"https://doi.org/10.1111/1440-1681.13327","url":null,"abstract":"<p><p>Personalized medicine, the treatment best suited for an individual, is a hot field of clinical research in the world. Many recent studies have shown that genetic variations have a great influence on the treatment. This study aimed to identify the distribution differences of very important pharmacogene (VIP) variants between the Tibetan population and the other 26 populations from the 1000 Genomes project. Based on the PharmGKB database, we successfully genotyped 50 VIP variants located in 27 genes in the Tibetan population. We also compared the genotype frequencies of VIP variants between Tibetan population and the other 26 populations. Without adjustment, the Chi-square test showed that the only significant variant between Tibetans and every other group was rs1801159 in dihydropyrimidine dehydrogenase (DPYD), followed by rs1800566 in NAD(P)H quinone dehydrogenase 1 (NQO1) and rs1051296 in solute carrier family 19 member 1 (SLC19A1). After Bonferroni's multiple adjustments, the genotype frequencies distribution of DPYD rs1801159 was found to be different in Tibetans compared to the other 26 groups, apart from ACB and ASW. Moreover, genetic structure/F-statistics (Fst) analysis and the phylogenetic tree illustrated that Tibetans had a closer affinity with CDX, CHB, CHS, JPT and KHV. Our data will complement pharmacogenomics information of the Tibetan population and provide theoretical support for the realization of individualized medical treatment for Tibetans in the future.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"668-678"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37851466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of escitalopram on an acetic acid-induced ulcerative colitis model.","authors":"Negar Firouzabadi,&nbsp;Nahid Alimoradi,&nbsp;Mohammad Najafizadeh,&nbsp;Parvaneh Najafizadeh","doi":"10.1111/1440-1681.13474","DOIUrl":"https://doi.org/10.1111/1440-1681.13474","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal (GI) disorder with an unknown aetiology and pathogenesis. Regarding the effectiveness of antidepressants on UC in animal models of depression and the known anti-inflammatory effects of escitalopram this study was conducted to evaluate the beneficial effects of escitalopram on an acetic acid-induced UC model without depression. UC model was induced by intra rectal (i.r.) administration of 4% acetic acid in rats after 24 hours of fasting. Animals were treated with three doses of escitalopram (5, 10 and 20 mg/kg). Prednisolone (4 mg/kg) was used as a reference drug in UC. Histological and oxidative stress markers were measured in all groups. Results showed significant increase in superoxide dismutase (SOD) activity and glutathione (GSH) levels, as well as significant decrease in myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, macroscopic factors (ulcer surface area, ulcer severity and weight-to-colon ratio) and microscopic and histological parameters (severity and extent of inflammation, cryptic destruction and severity of tissue involvement) in escitalopram treated rats (10, 20 mg/kg) compared to the UC group. In conclusion, the results of our study are in support of beneficial anti-inflammatory and antioxidant effects of escitalopram in UC.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"782-790"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25352176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenacissoside H promotes neurological recovery of cerebral ischaemia/reperfusion injury in mice by modulating inflammation and oxidative stress via TrkB pathway.","authors":"Rui Zhang,&nbsp;Cui Liu,&nbsp;Yang Li,&nbsp;Liang Chen,&nbsp;Jianfeng Xiang","doi":"10.1111/1440-1681.13398","DOIUrl":"https://doi.org/10.1111/1440-1681.13398","url":null,"abstract":"<p><p>Cerebral ischaemia/reperfusion (I/R)-induced acute brain injury remains a troublesome condition in clinical practice. The present study aimed to investigate the protective effect of tenacissoside H (TH) on I/R-induced cerebral injury in mice. Here, a mouse model of middle cerebral artery occlusion (MCAO) was established by an improved Longa-Zea method. TH was given by intraperitoneal injection once a day within 1 week before establishing the mouse MCAO model. The neurological functions of mice were evaluated and the apoptosis of neurons was also detected by the TUNEL method and Nissl's staining. ELISA and western blot were used to detect the expression of inflammatory factors, oxidation factors and proteins in the cerebral ischaemic cortex. The results revealed that TH dose-dependently reduced neurological impairment, neuron apoptosis and brain oedema induced by MCAO. Furthermore, TH attenuated the expression of pro-inflammatory cytokines (including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α), iNOS and nuclear factor (NF)-κB while increased production of anti-inflammatory cytokines (IL-4, IL-10 and BDNF) and proteins of tropomyosin-related kinase receptor B (TrkB) and PPARγ. Nevertheless, after the addition of TrkB inhibitor, the effects of TH above were mostly restrained. In conclusion, TH can protect mice against I/R-induced neurological impairments via modulating inflammation and oxidative stress through TrkB signalling.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"757-769"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38276975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of action of a diterpene alkaloid hypaconitine on cytotoxicity and inhibitory effect of BAPTA-AM in HCN-2 neuronal cells.","authors":"Shu-Shong Hsu,&nbsp;Yung-Shang Lin,&nbsp;Wei-Zhe Liang","doi":"10.1111/1440-1681.13482","DOIUrl":"https://doi.org/10.1111/1440-1681.13482","url":null,"abstract":"<p><p>Hypaconitine, a neuromuscular blocker, is a diterpene alkaloid found in the root of Aconitum carmichaelii. Although hypaconitine was shown to affect various physiological responses in neurological models, the effect of hypaconitine on cell viability and the mechanism of its action of Ca²⁺ handling is elusive in cortical neurons. This study examined whether hypaconitine altered viability and Ca²⁺ signalling in HCN-2 neuronal cell lines. Cell viability was measured by the cell proliferation reagent (WST-1). Cytosolic Ca²⁺ concentrations [Ca²⁺ ]_i was measured by the Ca²⁺ -sensitive fluorescent dye fura-2. In HCN-2 cells, hypaconitine (10-50 μmol/L) induced cytotoxicity and [Ca²⁺ ]_i rises in a concentration-dependent manner. Removal of extracellular Ca²⁺ partially reduced the hypaconitine's effect on [Ca²⁺ ]_i rises. Furthermore, chelation of cytosolic Ca²⁺ with BAPTA-AM reduced hypaconitine's cytotoxicity. In Ca²⁺ -containing medium, hypaconitine-induced Ca²⁺ entry was inhibited by modulators (2-APB and SKF96365) of store-operated Ca²⁺ channels and a protein kinase C (PKC) inhibitor (GF109203X). Hypaconitine induced Mn²⁺ influx indirectly suggesting that hypaconitine evoked Ca²⁺ entry. In Ca²⁺ -free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin abolished hypaconitine-induced [Ca²⁺ ]_i rises. Conversely, treatment with hypaconitine inhibited thapsigargin-induced [Ca²⁺ ]_i rises. However, inhibition of phospholipase C (PLC) with U73122 did not inhibit hypaconitine-induced [Ca²⁺ ]_i rises. Together, hypaconitine caused cytotoxicity that was linked to preceding [Ca²⁺ ]_i rises by Ca²⁺ influx via store-operated Ca²⁺ entry involved PKC regulation and evoking PLC-independent Ca²⁺ release from the endoplasmic reticulum. Because BAPTA-AM loading only partially reversed hypaconitine-induced cell death, it suggests that hypaconitine induced a second Ca²⁺ -independent cytotoxicity in HCN-2 cells.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"801-810"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25386067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vasodilatory action of trans-4-methoxy-β-nitrostyrene in rat isolated pulmonary artery.","authors":"Loeste Arruda-Barbosa,&nbsp;Alfredo Augusto Vasconcelos-Silva,&nbsp;Rosivaldo Santos Borges,&nbsp;Gloria Pinto Duarte,&nbsp;Pedro Jorge Caldas Magalhães,&nbsp;Saad Lahlou","doi":"10.1111/1440-1681.13467","DOIUrl":"https://doi.org/10.1111/1440-1681.13467","url":null,"abstract":"<p><p>Trans-4-methoxy-β-nitrostyrene (T4MN) induced more potent vasorelaxant effects in resistance arteries from hypertensive rats than its parent drug, β-nitrostyrene 1-nitro-2-phenylethene (NPe). To better understand the influence of insertion of the electron-releasing methoxy group in the aromatic ring of NPe, we investigated vasorelaxant effects of T4MN in isolated pulmonary artery and compared them with those of NPe in view of the potential interest of T4MN in pulmonary arterial hypertension. T4MN and NPe both caused concentration-dependent vasorelaxation in pulmonary artery rings pre-contracted with either phenylephrine (1 µmol/L) or KCl (60 mmol/L), an effect unaffected by endothelium removal. In endothelium-intact preparations pre-contracted with phenylephrine, the vasorelaxant effect of T4MN was more potent than that of NPe. However, unlike NPe, this effect was significantly reduced following pretreatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 µmol/L, a guanylate cyclase inhibitor) or tetraethylammonium (5 mmol/L, a potassium channel blocker). T4MN abolished the CaCl₂ -induced contractions in pulmonary artery preparations stimulated with phenylephrine (PHE) under Ca²⁺ -free conditions in the presence of verapamil, to preferentially activate receptor-operated calcium channels. From these findings, we propose that T4MN evokes endothelium-independent vasorelaxant effects in isolated rat pulmonary artery, partially by inhibiting Ca²⁺ influx through L-type Ca²⁺ channels, as well as by activating soluble guanylate cyclase and potassium channels. The present results suggest the therapeutic potential of T4MN in treating pulmonary arterial hypertension.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"717-725"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38803333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the SphK-S1P-S1PRs pathway in invasion of the nervous system by SARS-CoV-2 infection.","authors":"Yuehai Pan,&nbsp;Fei Gao,&nbsp;Shuai Zhao,&nbsp;Jinming Han,&nbsp;Fan Chen","doi":"10.1111/1440-1681.13483","DOIUrl":"https://doi.org/10.1111/1440-1681.13483","url":null,"abstract":"<p><p>Global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing. Before an effective vaccine is available, the development of potential treatments for resultant coronavirus disease 2019 (COVID-19) is crucial. One of the disease hallmarks is hyper-inflammatory responses, which usually leads to a severe lung disease. Patients with COVID-19 also frequently suffer from neurological symptoms such as acute diffuse encephalomyelitis, brain injury and psychiatric complications. The metabolic pathway of sphingosine-1-phosphate (S1P) is a dynamic regulator of various cell types and disease processes, including the nervous system. It has been demonstrated that S1P and its metabolic enzymes, regulating neuroinflammation and neurogenesis, exhibit important functions during viral infection. S1P receptor 1 (S1PR1) analogues including AAL-R and RP-002 inhibit pathophysiological responses at the early stage of H1N1 virus infection and then play a protective role. Fingolimod (FTY720) is an S1P receptor modulator and is being tested for treating COVID-19. Our review provides an overview of SARS-CoV-2 infection and critical role of the SphK-S1P-SIPR pathway in invasion of SARS-CoV-2 infection, particularly in the central nervous system (CNS). This may help design therapeutic strategies based on the S1P-mediated signal transduction, and the adjuvant therapeutic effects of S1P analogues to limit or prevent the interaction between the host and SARS-CoV-2, block the spread of the SARS-CoV-2, and consequently treat related complications in the CNS.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"637-650"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25354658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of bioequivalence of two flurbiprofen axetil injections: A randomized, open-label, double-cycle, and crossover study.","authors":"Jin Wang,&nbsp;Liuhan Dong,&nbsp;Rui Wang,&nbsp;Yun Cai","doi":"10.1111/1440-1681.13479","DOIUrl":"https://doi.org/10.1111/1440-1681.13479","url":null,"abstract":"<p><p>Flurbiprofen is a non-steroidal anti-inflammatory drug. We evaluated the bioequivalence of a new formulation of flurbiprofen axetil for injection and the reference drug ROPION (another kind of flurbiprofen axetil injection marketed for use) in healthy Chinese subjects. This is a single-centre, randomized, open-label, single-dose, two period crossover bioequivalence study. Each subject received a single intravenous injection at the dose of 50 mg under fasting. The drug was dissolved in 100 mL normal saline, and the injection was completed in 15 minutes. There was a 7-day washout period between the two administrations. The plasma concentrations of flurbiprofen were measured by LC-MS/MS, and descriptive statistics were used to describe the safety outcomes including adverse events (AEs) and adverse drug reactions (ADRs). Twenty-four subjects were enrolled in this study. Mean values of primary PK parameters (T_max , C_max , AUC_0-t , AUC_0-∞ , λ_z , T_1/2 ) were similar (P > 0.05). T_max for both products is 0.3 hours. The 90% confidence intervals (CIs) for peak concentration C_max ranged between 96.87% and 100.42%, and the area under curve AUC_0-t and AUC_0-∞ ranged between 99.09% and 104.29% and 98.97% and 104.29%, respectively. The 90% CIs for the geometric means and ratios of primary PK endpoints of flurbiprofen axetil injection to reference drug ranged between 98.97% and 104.29%. The adverse event rate of the test product was 8.3% and no serious adverse events (SAE) occurred in this clinical study. We concluded that the test product and the reference drug were bioequivalent and the safety was high in healthy Chinese subjects.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"660-667"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25386012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of tegaserod, a gastrokinetic agent, on voltage-gated K⁺ channels in rabbit coronary arterial smooth muscle cells.","authors":"Jin Ryeol An,&nbsp;Hee Seok Jung,&nbsp;Mi Seon Seo,&nbsp;Minji Kang,&nbsp;Ryeon Heo,&nbsp;Hongzoo Park,&nbsp;Geehyun Song,&nbsp;Won-Kyo Jung,&nbsp;Il-Whan Choi,&nbsp;Won Sun Park","doi":"10.1111/1440-1681.13477","DOIUrl":"https://doi.org/10.1111/1440-1681.13477","url":null,"abstract":"<p><p>Tegaserod, a gastroprokinetic agent, is used to treat irritable bowel syndrome. Despite its extensive clinical use, little is known about the effects of tegaserod on vascular ion channels, especially K⁺ channels. Therefore, we examined the effects of tegaserod on voltage-gated K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells using the whole-cell patch-clamp technique. Tegaserod inhibited Kv channels in a concentration-dependent manner with an IC₅₀ value of 1.26 ± 0.31 µmol/L and Hill coefficient of 0.81 ± 0.10. Although tegaserod had no effect on the steady-state activation curves of the Kv channels, the steady-state inactivation curve was shifted toward a more negative potential. These results suggest that tegaserod inhibits Kv channels by influencing their voltage sensors. The recovery time constant of channel inactivation was extended in the presence of tegaserod. Furthermore, application of train steps (1 and 2 Hz) in the presence of tegaserod progressively increased the inhibition of Kv currents suggesting that tegaserod-induced Kv channel inhibition is use (state)-dependent. Pretreatment with a Kv1.5 subtype inhibitor suppressed the Kv current. However, additional application of tegaserod did not induce further inhibition. Pretreatment with a Kv2.1 or Kv7 inhibitor did not affect the inhibitory effect of tegaserod on Kv channels. Based on these results, we conclude that tegaserod inhibits vascular Kv channels in a concentration- and use (state)-dependent manner independent of its own functions. Furthermore, the major Kv channel target of tegaserod is the Kv1.5 subtype.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"748-756"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25401055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed blockage of prostaglandin EP₄ receptors can reduce dedifferentiation, epithelial-to-mesenchymal transition and fibrosis following acute kidney injury.","authors":"Mohamed Abouelkheir,&nbsp;Dalia A Shabaan,&nbsp;Mohamed Awad Shahien","doi":"10.1111/1440-1681.13478","DOIUrl":"https://doi.org/10.1111/1440-1681.13478","url":null,"abstract":"<p><p>Dedifferentiation of tubular epithelial cells is involved in both regeneration and fibrosis following acute kidney injury (AKI). Prostaglandin E₂ receptor 4 (EP₄ ) antagonist can inhibit the dedifferentiation of renal tubular cells. The present study investigated whether the time of blockage of EP₄ receptors, using grapiprant, could affect the tubular regeneration or interstitial fibrosis in AKI. Cisplatin was used to induce AKI in 72 C57BL/6 adult female mice. Animals were assigned to four groups; control, cisplatin-treated, cisplatin-treated with early grapiprant intervention and cisplatin-treated with late grapiprant intervention. AKI was assessed by kidney function tests and histopathology. Fibrosis was evaluated by Masson's trichrome and alpha smooth muscle actin (α-SMA) expression. Markers of dedifferentiation, CD133, and epithelial to mesenchymal transition (EMT), vimentin were assessed. Early intervention with grapiprant significantly ameliorated AKI more efficiently than late intervention. However, even late intervention was useful in reducing the overall fibrosis as demonstrated by Masson's trichrome and α-SMA expression. In both grapiprant-treated groups, a parallel reduction of dedifferentiation (CD133) and EMT (vimentin) was evident. It seems that the progressive fibrotic changes that follow AKI could still be reduced possibly by targeting dedifferentiation and/or EMT.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"791-800"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25414469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nebivolol protects against cyclophosphamide-induced nephrotoxicity through modulation of oxidative stress, inflammation, and apoptosis.","authors":"Hanaa Wanas,&nbsp;Mohamed El-Shabrawy,&nbsp;Amal Mishriki,&nbsp;Hisham Attia,&nbsp;Mohamed Emam,&nbsp;Basma Emad Aboulhoda","doi":"10.1111/1440-1681.13481","DOIUrl":"https://doi.org/10.1111/1440-1681.13481","url":null,"abstract":"<p><p>The usefulness of cyclophosphamide (CP) in the treatment of multiple human malignancies and immunological diseases is hindered by the danger of developing nephrotoxicity. The toxic metabolites of CP are suggested to be responsible for oxidative stress resulted from the production of reactive oxygen species (ROS) and stimulation of lipid peroxidation. Nebivolol (NEB) is a third-generation selective B₁ adrenoceptor antagonist, but it has also various pharmacological properties such as anti-inflammation, anti-apoptotic, and antioxidant activities. Thus, the present study aims to explore the potential protective effect of NEB against CP-induced nephrotoxicity. A cumulative dose of CP (75 mg/kg) was administered to albino rats by intraperitoneal injection. The protective effect of NEB was investigated by co-administration of NEB (10 mg/kg orally daily). Administration of NEB with CP significantly improved renal functions and reduced the oxidative renal changes induced by CP injection. Co-administration of NEB ameliorated apoptosis and inflammatory markers that were markedly exaggerated by CP. Our results indicated that NEB could be used as a protective agent against CP-induced nephrotoxicity.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"811-819"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25373096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}