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Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib in vitro by altering cell bioenergetics 被引量:4
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作者 Jelena Grahovac Tatjana Srdic-Rajic +3 位作者 Juan Francisco Santibanez Marijana Pavlovic Milena Cavic Sinisa Radulovic1 《Cancer Biology & Medicine》 SCIE CAS CSCD 2019年第2期247-263,共17页
Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents ... Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment.Methods: Expression of AGTR1 and PPARγ m RNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method.Results: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis.Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment.Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression. 展开更多
关键词 MELANOMA telmisartan apoptosis MITOCHONDRIA reactive oxygen species targeted therapy
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Simultaneous determination of telmisartan and amlodipine in human plasma by LC-MS/MS and its application in a human pharmacokinetic study 被引量:8
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作者 Vasu Babu Ravi Jaswanth Kumar Inamadugu +2 位作者 Nageswara Rao Pilli Vudagandla Sreenivasulu Venkateswarlu Ponneri 《Journal of Pharmaceutical Analysis》 CAS 2012年第5期319-326,共8页
A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for the simultaneous quantification of telmisartan and amlodipine in human plasma.... A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for the simultaneous quantification of telmisartan and amlodipine in human plasma. Carbamazepine was used as an internal standard. Analytes and the internal standard were extracted from human plasma by solid-phase extraction technique using Waters Oasis HLB 1 cm3 (30 mg) extraction cartridge. The reconstituted samples were chromatographed on a Hypurity advance C18 column (50mm × 4.6mm, 5 gm) using a mixture of acetonitrile -5 mM ammonium acetate buffer (pH-4.0) (50:50, v/v) as the mobile phase at a flow rate of 0.8mL/min. The calibration curve obtained was linear (r_〉0.99) over the concentration range of 2.01-400.06 ng/mL for telmisartan and 0.05 -10.01 ng/mL for amlodipine. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The proposed method was found to be applicable to clinical studies. 展开更多
关键词 telmisartan AMLODIPINE Human plasma Solid-phase extraction LC-MS/MS PHARMACOKINETICS
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Telmisartan Reduced Cerebral Edema by Inhibiting NLRP_3 Inflammasome in Mice with Cold Brain Injury 被引量:5
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作者 魏欣 胡晨晨 +2 位作者 张亚丽 姚尚龙 毛卫克 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2016年第4期576-583,共8页
The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury(TBI) and the potential mechanisms related to the nucleotide-binding oligomerization... The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury(TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain(NOD)-like receptor(NLR) pyrin domain-containing 3(NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier(BBB) integrity, the neurological function and histological injury were assessed, at the same time, the m RNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein(ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation. 展开更多
关键词 telmisartan traumatic brain injury cerebral edema NLRP3 inflammasome inflammation
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Telmisartan prevents high-fat diet-induced hypertension and decreases perirenal fat in rats 被引量:3
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作者 Yaping Wang Yan Song +2 位作者 Meng Suo Xin Jin Gang Tian 《The Journal of Biomedical Research》 CAS 2012年第3期219-225,共7页
We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel-... We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel- misartan group (n = 9) and the high-fat diet group (n = 10). The control group consisted of age-matched rats on a regular diet (n = 10). At the end of the treatment, the body weight, blood pressure, insulin sensitivity and serum adiponectin levels of all rats were examined, and their visceral fat was extracted and weighed. Our results showed that telmisartan improved insulin resistance and dyslipidemia and increased serum adiponectin levels. Telmisar- tan also lowered both systolic blood pressure and diastolic blood pressure, and decreased the accumulation of perirenal fat associated with high-fat diet. Furthermore, telmisartan increased adiponectin mRNA expression in the perirenal fat. Correlation analysis showed that both systolic blood pressure and diastolic blood pressure were positively correlated with perirenal fat. These effects of telmisartan may be mediated through decreases in perirenal fat and contributed to the improvement of perirenal fat function. Our findings suggested a strong link between perirenal fat and high-fat diet-induced hypertension, and identified telmisartan as a potential drug for the treatment of obesity-related hypertension. 展开更多
关键词 telmisartan high-fat diet HYPERTENSION perirenal fat ADIPONECTIN
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Telmisartan but not Valsartan Inhibits TGF-β-mediated Accumulation of Extracelluar Matrix via Activation of PPARγ 被引量:3
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作者 姚颖 邹荣 +8 位作者 刘晓城 江晶晶 黄倩 何泳 李萌 王世宣 周剑峰 马丁 徐刚 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2008年第5期543-548,共6页
Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the sup... Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the suppression of mesangial cell activation is not fully understood. Since activation of peroxisome proliferators-activated receptor γ (PPARγ) has been proposed to decrease the effects of transforming growth factor-β (TGF-β) on glomerulosclerosis, we examined here whether and how telmisartan, an angiotensin Ⅱ type 1 receptor blocker with PPARγ-modulating activity, inhibited TGF-β-induced glomerulosclerosis in rat glomerular mesangial cells. Protein levels of PPARγ were detected by Western blot. Activation of PPARγ response element (PPRE) was analyzed by luciferase assays. Deposition of extracelluar matrix was tested by confocol laser scanning. The results showed that telmisartan, but not valsartan, another angiotensin Ⅱ type 1 receptor blocker, up-regulated PPARγ protein levels in a dose-dependent manner (P〈0.05). Activation of PPRE, represented by luciferase activity, was also increased with higher concentration of telmisartan in a dose-dependent manner (P〈0.05). Furthermore, telmisartan inhibited TGF-β-induced α-smooth muscle actin expression and collagen IV secretion in mesangial cells. GW9662, an inhibitor of PPAR-γ, blocked the inhibitory effects of telmisartan on TGF-β-induced glomerulosclerosis in mesangial cells. Our study indicates a benefit of telmisartan as a PPARγ agonist against TGF-β-induced mesangial cells activation in renal glomerulus. It may provide possibility that telmisartan works as a potential agent against diabetic nephropathy and hypertensive renal disease. 展开更多
关键词 telmisartan GLOMERULOSCLEROSIS peroxisome proliferators-activated receptorγ
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Telmisartan Protects against Insulin Resistance by Attenuating Inflammatory Response in Rats 被引量:2
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作者 徐西振 殷晓明 +3 位作者 冯文静 李耕 汪道文 凃玲 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2011年第3期317-323,共7页
This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism.A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups... This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism.A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups at random:ND group(n=10) and HD group(n=10),in which the rats were given a normal chow diet or a high-fat diet for 20 weeks following a one-week adaptation;ND+telmisartan(n=10) group and HD+telmisartan group(n=10),in which the rats were initially administered in the same way as the ND or HD group,and then they were orally gavaged with telmisartan(5 mg/kg daily) additionally for 5 weeks.Related inflammatory factors were measured by ELISA.Monocyte chemotactic protein 1(MCP-1),phosphorylated JNK and IκB-α expressions in both adipose and liver were detected by Western blotting.CRP and angiotensin Ⅱ receptor 1(AT1) mRNA expressions in both adipose and liver were determined by RT-PCR.The results showed that telmisartan administration in vivo reversed insulin resistance as evidenced by a decrease in plasma fasting glucose levels,plasma fasting insulin levels and homeostasis model of assessment-insulin resistance(HOMA-IR).Furthermore,telmisartan administration significantly reduced serum CRP,TNF-α and IL-1β levels,and elevated serum IL-10 levels.It was also found to hamper the high-fat diet-induced increase in CRP mRNA,AT1 mRNA and MCP-1,and decrease in IκB-α in both adipose and liver.It was concluded that telmisartan administration in vivo may improve insulin resistance through attenuated inflammatory response pathways. 展开更多
关键词 telmisartan insulin resistance INFLAMMATION OBESITY
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Telmisartan Attenuates the Growth of Epithelium-like Cells and Glomerular Injury in Spontaneously Hypertensive Rats 被引量:1
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作者 Zhi ZHANG Fa-zhan WANG +1 位作者 Zai-xin LI Xiang-rong SONG 《Current Medical Science》 SCIE CAS 2021年第3期498-504,共7页
The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis ... The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth. 展开更多
关键词 HYPERTENSION epithelium-like cell glomerular injury telmisartan spontaneously hypertensive rats(SHRs)
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Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model 被引量:1
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作者 Francielle Graus-Nunes Felipe de Oliveira Santos +3 位作者 Thatiany de Souza Marinho Carolline Santos Miranda Sandra Barbosa-da-Silva Vanessa Souza-Mello 《World Journal of Hepatology》 2019年第4期359-369,共11页
BACKGROUND Obesity has been associated with hepatic overexpression of the renin-angiotensin system(RAS).AIM To evaluate the action of two angiotensin II(ANGII) receptor blockers(losartan or telmisartan) on the modulat... BACKGROUND Obesity has been associated with hepatic overexpression of the renin-angiotensin system(RAS).AIM To evaluate the action of two angiotensin II(ANGII) receptor blockers(losartan or telmisartan) on the modulation of local hepatic RAS and the resulting metabolic effects in a diet-induced obesity murine model.METHODS Twenty C57 BL/6 mice were randomly divided into two nutritional groups for 10 wk: control group(C, n = 5, 10% of energy as fat) or high-fat group(HF, n = 15,50% of energy as fat). After treatment started, the HF group was randomly divided into three groups: untreated HF group(n = 5), HF treated with losartan(HFL, n = 5) and HF treated with telmisartan(HFT, n = 5). The treatments lasted for 5 wk, and the dose was 10 mg/kg body mass.RESULTS HF diet induced body mass gain(+28%, P < 0.0001), insulin resistance(+69%, P =0.0079), high hepatic triacylglycerol(+127%, P = 0.0004), and overexpression of intrahepatic angiotensin-converting enzyme(ACE) 1/ANGII type 1 receptor(AT1 r)(+569.02% and +141.40%, respectively, P < 0.0001). The HFL and HFT groups showed higher ACE2/rMAS gene expression compared to the HF group(ACE2: +465.57%, P = 0.0002 for HFL and +345.17%, P = 0.0049 for HFT; rMAS:+711.39%, P < 0.0001 for HFL and +539.75%, P < 0.0001 for HFT), followed by reduced insulin/glucose ratio(-30% for HFL and-33% for HFT, P = 0.0181),hepatic triacylglycerol levels(-28%, P = 0.0381 for HFL; and-45%, P = 0.0010 for HFT, and Plin2 expression.CONCLUSION Modulation of the intrahepatic RAS, with favored involvement of the ACE2/rMAS axis over the ACE1/AT1 r axis after losartan or telmisartan treatments, caused hepatic and metabolic beneficial effects as demonstrated by reduced hepatic triacylglycerol levels coupled with reduced PLIN 2 expression and improved glycemic control. 展开更多
关键词 Liver telmisartan LOSARTAN OBESITY Angiotensin type 1 receptor C57BL/6 mouse
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Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance
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作者 Dongxiu Xu Junfa Liu Cuiling Ji Liping Zhou Hong Guo 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2007年第3期149-152,共4页
Objective To investigate the effects of telmisartan on the blood glucose,blood lipid,blood insulin,and insulin resistance in the hypertensive patients with dyslipidemia,and also its effect on controlling blood pressur... Objective To investigate the effects of telmisartan on the blood glucose,blood lipid,blood insulin,and insulin resistance in the hypertensive patients with dyslipidemia,and also its effect on controlling blood pressure. Patients and Methods A total of 96 hypertensive patients(34 females,62 males) with dyslipidemia were included(mean age 51.2±9.6,range 42-65 years) . Patients were randomized to receive either telmisartan 80 mg/day(n=46) or enalapril 10 mg/day(n=50) for 6 months. The levels of blood pressure(BP) ,heart rate(HR) ,and biochemical data were measured before therapy and at the end of the 3-month treatment and 6-month treatment,respectively. Meanwhile,insulin resistance was evaluated by using a homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity(HOMA-IS) . Results In the telmisartan group,the mean blood pressure was obviously lower than that of pre-therapy(P< 0.05) ,and the levels of triglyceride(TG) ,HOMA-IR,and HOMA-IS were all obviously lower than those of pre-therapy and of the enalapril group at the end of the 3-month-treatment period(P<0.05) . After 6 months of treatment,the levels of TG,HOMA-IR,and HOMA-IS in the telmisartan group were significantly lower in comparison with those of pre-therapy,the enalapril group(P<0.01) ,and 3-month-treatment(P<0.05) . Post-prandial12 hour blood glucose(P2HBG) in the telmisartan group decreased significantly after 6-month treatment compared with that of pre-therapy and the enalapril group(P<0.05) . The level of high density lipoprotein(HDL) cholesterol was significantly higher after 6-month treatment in the telmisartan group than with pre-therapy and the enalapril group(P<0.05) . Conclusions Telmisartan could not only control blood pressure steadily and effectively,but also decrease blood TG,increase HDL cholesterol and insulin sensitivity,and lower insulin resistance. 展开更多
关键词 telmisartan HYPERTENSION LIPID metabolism INSULIN resistance
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Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study
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作者 Pinaki Sengupta Bappaditya Chatterjee +2 位作者 Uttam Kumar Mandal Bapi Gorain Tapan Kumar Pal 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2017年第6期381-387,共7页
Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO) and telmisartan (TLM) combination can be beneficial in effective control of cardiovascu... Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO) and telmisartan (TLM) combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC-MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005-10 pg/mL with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%-106.10%. The inlxa- and inter-day precision ranged from 2.32% to 10.14% and 5.02% to 8.12%, respectively. The method was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method is expected to have significant usefulness in future. 展开更多
关键词 LC-MS/MS Rat plasma Pharmacokinetic applicability telmisartan PIOGLITAZONE Pharmacokinetic application
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Protective effect of telmisartan on rats with renal failure and its mechanism
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作者 Zhi-Kui Wang Zhen-Ying Liu Hai-Bo Yu 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2015年第6期497-500,共4页
Objective:To study the protective effect of telmisartan on rats with renal failure and its mechanism.Methods:60 Wistar rats were chosen as study objective,and were divided into4 groups randomly:15 in group A(sham oper... Objective:To study the protective effect of telmisartan on rats with renal failure and its mechanism.Methods:60 Wistar rats were chosen as study objective,and were divided into4 groups randomly:15 in group A(sham operation group).15 in group B(model group),15 in group C(telmisartan group) and 15 in group D(telmisartan+GW9962 group).The difference of survival rate,blood-urine biochemical indexes,renal pathological change,and the expression level of PPAR γ and nNOS were ompared.Results:After 12 weeks,the survival rate of group A was 93.33% (14/15),that of group B was 46.67% (7/15),that of group C was86.67% (13/15),that of group D was 60.00% (9/15),and the difference among 4 groups had statistical significance(P<0.05).After 1 week,the difference of Scr,that of BUN and that of24 h protein urine among 4 groups was not statistical significant(P>0.05);after 3 weeks,6 weeks and 12 weeks,these difference was statistical significant(P<0.05).The difference of blood-urine biochemical indexes,that of renal pathological change,and that of the expression level of PPAR γ and nNOS was statistical significant(P<0.05).Conclusions:Telmisartan has protective effect on renal failure caused by 5/6 nephrectomy,which might be relative to the expression level of PPAR γ and nNOS. 展开更多
关键词 telmisartan 5/6 NEPHRECTOMY RENAL FAILURE
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Angiotensin receptor blocker telmisartan promotes M2 microglia polarizatior
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《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期79-79,共1页
Aim Brain inflammation plays an important role in the pathophysiology of many psychiatric and neuro- logical diseases. Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 mi- c... Aim Brain inflammation plays an important role in the pathophysiology of many psychiatric and neuro- logical diseases. Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 mi- croglia activation. The ARB telmisartan suppresses neuroinflammation in cultured neuronal cells. We wished to clarify whether telmisartan prevents microglia-mediated neuroinflammation through microglia polarization to an anti- inflammatory M2 phenotype. Methods The gene expression of M1 markers and M2 markers was measured by RT- PCR. The AMPK phosphorylation level and M2 marker CD206 protein expression were determined by Western blot. TNF-α and IL-10 release was measured by ELISA. The gene knowdown was performed by the siRNA transfec- tion experiment. Results Our results demonstrated that telmisartan promoted M2 polarization in LPS-stimulated BV2 and primary microglia cells. The promoting effects of telmisartan on M2 polarization were attenuated by an AMP-activated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation partici- pates on telmisartan effects. Furthermore, telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPS-induced neuroinflammation. Conclusion Our results indicate that telmisartan can be con- sidered as a novel AMPK activator, suppressing neuroinflammation by promoting microglia M2 polarization. Telmis- artan may provide a novel and safe therapeutic approach for the treatment of brain disorders associated with neuroin- flammation. 展开更多
关键词 telmisartan MICROGLIA polarization AMP-activated protein KINASE NEUROINFLAMMATION
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Lacidipin和Telmisartan用于高血压治疗
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《德国临床用药》 1999年第2期15-18,共4页
关键词 高血压 Lacidipin telmisartan 药物疗法 新药
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Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance
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作者 Olabode Oladeinde 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2007年第3期153-154,共2页
  The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patie...   The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patients;1 post hoc studies have shown reductions in new onset type 2 diabetes mellitus (DM). …… 展开更多
关键词 high CVD Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance ARB IFG
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Development and Validation of Bioanalytical Method for Determination of Telmisartan and Hydrochlorothiazide Using HPTLC in Human Plasma
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作者 Ambadas R. Rote Poonam R. Sonavane 《American Journal of Analytical Chemistry》 2012年第11期774-778,共5页
A simple, sensitive, rapid and economic high performance thin layer chromatographic method has been developed for determination of telmisartan and hydrochlorothiazide in human plasma using paracetamol as an internal s... A simple, sensitive, rapid and economic high performance thin layer chromatographic method has been developed for determination of telmisartan and hydrochlorothiazide in human plasma using paracetamol as an internal standard. The plasma sample was extracted using mixture of methanol-acetonitrile (3.0:0.1, v/v). A concentration range from 200, 400, 600, 800, 1000, 1200 ng/spots were used for calibration curve of hydrochlorothiazide and telmisartan respectively. The percent recovery of telmisartan and hydrochlorothiazide was found to be75.98 and 81.91%. The mobile phase consists of chloroform: methanol: toluene (8:2:4 v/v/v). Densitometric analysis was carried out at wavelength 278 nm. The Rf values for hydrochlorothiazide, paracetamol and telmisartan were 0.28 ± 0.05, 0.50 ± 0.05, 0.66 ± 0.05 respectively. The stability of telmisartan and hydrochlorothiazide in plasma were confirmed during three freeze-thaw cycles (?20?C), on bench during 24 hours and post preparative during 48 hours. The proposed method was validated statistically and by performing recovery study for determination of telmisartan and hydrochlorothiazide in human plasma. 展开更多
关键词 HPTLC telmisartan HYDROCHLOROTHIAZIDE Human Plasma LIQUID-LIQUID Extraction
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Ultra-Sensitive LC-MS/MS Method for the Trace Level Quantification of Six Potential Genotoxic Nitrosamine Impurities in Telmisartan
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作者 Kartheek Srinivas Chidella Vijaya Bharathi Dasari Jayashree Anireddy 《American Journal of Analytical Chemistry》 2021年第6期227-240,共14页
Nitrosamine impurities are potentially genotoxic which are considered under cohort of concern as per ICH M7 guidelines and need to be controlled at trace levels during quantification in drug substances and drug produc... Nitrosamine impurities are potentially genotoxic which are considered under cohort of concern as per ICH M7 guidelines and need to be controlled at trace levels during quantification in drug substances and drug products for safe human consumption. Recent regulatory requirements also suggest the need to have highly sensitive analytical methods for the accurate quantification of Nitrosamine impurities. In this paper we have presented simple, rapid and ultra-sensitive LC-MS/MS method for six potential genotoxic nitrosamine impurities: N-Nitroso dimethyl amine (NDMA), N-Nitroso diethyl amine (NDEA), N-Nitroso Ethyl Iso propylamine (NEIPA), N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) N-Nitroso diisopropylamino (NDIPA) and N-Nitroso dibutyl amine (NDBA) with a LOQ of 0.004 ppm. Chromatographic separation is achieved using Zorbax SB C18 150 × 3.0 mm, 3.5 μ column with 0.1% formic acid in water as mobile phase A and 0.1% formic acid in methanol as mobile phase B at a flow rate of 0.3 ml/min using gradient mode of elution at a total run time of 18 minutes. Six nitrosamine impurities are successfully ionized and quantified in positive mode of atmospheric pressure chemical ionization (APCI) using multiple reaction monitoring (MRM). Method validation is performed as per ICH guidelines evaluating the limit of quantification and detection and found to give good S/N ratios with good linearity range of 0.002 - 2 ppm with regression coefficient >0.99 for all the six nitrosamine impurities. Method recoveries are established using three-step sample preparation protocol and are found to be satisfactory within 80% - 120%. The method can be used routinely applied for the detection of Nitrosamines in Telmisartan at a concentration of 1.5 ng/ml (0.03 ppm with respect to telmisartan concentration of 50 mg/ml). 展开更多
关键词 NITROSAMINE NDMA GENOTOXIC LC-MS/MS telmisartan IMPURITIES
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Effectiveness of Telmisartan as an Adjunct to Metformin in Treating Type II Diabetes Mellitus in Rats
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作者 Rania M. Salama Mona F. Schaalan +2 位作者 Moushira E. Ibrahim Amani E. Khalifa Alaaeldin A. Elkoussi 《Open Journal of Endocrine and Metabolic Diseases》 2013年第3期186-196,共11页
The monitoring reports of most patients with type II diabetes mellitus (T2DM) revealed that monotherapy with metformin could not achieve long-term glycemic control. Thus, we designed this study aiming to investigate t... The monitoring reports of most patients with type II diabetes mellitus (T2DM) revealed that monotherapy with metformin could not achieve long-term glycemic control. Thus, we designed this study aiming to investigate the effect of telmisartan, a unique AT1 receptor antagonist and a partial agonist of peroxisome-proliferator activated receptor gamma (PPARγ), individually and as an adjunct to metformin, on a rat model that simulates the metabolic characteristics of human T2DM. Adult male Wistar rats were fed high-fat, high-fructose diet (HFFD) for 8 weeks followed by a single low dose of streptozotocin (STZ) (35 mg/kg/day, i.p.) rendering them diabetic and insulin resistant. The effectiveness of both drugs and their combination was tested by assessing the changes in the levels of serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid profile and adiponectin. In addition, the level of reduced glutathione (GSH) in the liver, was investigated. Results showed that the addition of telmisartan to metformin successfully restored serum glucose back to normal levels and corrected the altered serum total cholesterol (TC), triglycerides (TG) and adiponectin, emphasizing the potential role of telmisartan as an adjunct to metformin. 展开更多
关键词 Type II Diabetes Mellitus Insulin Resistance HIGH-FAT High-Fructose Diet METFORMIN telmisartan Peroxisome-Proliferator Activated Receptor Gamma
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Bioequivalence Study of Two Formulations of Telmisartan 40 mg Tablets in Healthy Adult Bangladeshi Subjects under Fasting Conditions
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作者 Alimur Reza Sabrina Akter Tushi +3 位作者 Nithon Chandra Sahana Uttom Kumar Bhowmik Abdullah Al Shafi Majumder Arifa Akram 《Advances in Bioscience and Biotechnology》 CAS 2022年第9期419-427,共9页
Background: Telmisartan is a highly variable drug which is used to treat hypertension. This study compared to compare the bioavailability of two 40 mg Telmisartan tablets in adult and healthy Bangladeshi subjects. Mat... Background: Telmisartan is a highly variable drug which is used to treat hypertension. This study compared to compare the bioavailability of two 40 mg Telmisartan tablets in adult and healthy Bangladeshi subjects. Materials and Method: This study was open label, randomized, laboratory blind, single dose, three periods, two treatments, three-sequence, partial-replicate, crossover and comparative oral bioavailability study. In this study, 18 Bangladeshi subjects were enrolled and 17 subjects were completed. Serial blood samples were collected up to 96 hours following drug administration. By using Liquid Chromatography Mass Spectrometry (LC-MS/MS) method, plasma concentrations of Telmisartan were determined. Results: The two formulations of Telmisartan were considered bioequivalent if 90% Confidence Interval (CI) fall within the range of 80.00% - 125.00% for AUC parameters and reference-scaled-average bioequivalence of 69.84% - 143.19% for C<sub>max</sub>. The 90% Confidence Interval for C<sub>max</sub>, AUC<sub>0-t</sub> & AUC<sub>0-∞</sub> was found 84.88% - 107.79%, 89.76% - 109.55%, and 91.20% - 114.52%, respectively. Conclusion: According to rate and extent of absorption with the single dose of Reference Product (R): Micardis<sup><sup><sup>&reg;</sup></sup></sup> 40 mg Tablet, under fasting conditions, a single dose of Telmisartan 40 mg Tablet is bioequivalent. 展开更多
关键词 BIOEQUIVALENCE telmisartan Micardis Pharmacokinetics
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Triple drug combination of telmisartan, amlodipine and hydrochlorothiazide in the treatment of essential hypertension
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作者 Manish Maladkar Vijay Kumar Verma +4 位作者 Keshav A. Narsikar Rajan D. Walinjkar W. R. Patil N. J. S. Saggu Suresh P. Kulkarni 《Open Journal of Internal Medicine》 2012年第2期67-71,共5页
Background: Triple drug therapy comprising angiotensin receptor blocker (ARB), calcium channel blocker (CCB) and hydrochlorothiazide (HCT) effectively controls essential hypertension as evident from the literature. Th... Background: Triple drug therapy comprising angiotensin receptor blocker (ARB), calcium channel blocker (CCB) and hydrochlorothiazide (HCT) effectively controls essential hypertension as evident from the literature. This study was undertaken to assess the efficacy and safety of triple combination compared to the dual drug therapy. Methodologies: A total of 220 male and female patients with essential hypertension were enrolled in the study. The patients were divided into two groups. Group A received a bilayer tablet of FDC of Telmisartan + Amlodipine + HCT and group B received FDC tablet of Telmisartan + HCT. Both the treatments were administered once daily for twelve weeks. The patients were asked to follow-up on week 1, 2, 4, 6, 8 and 10 for periodic efficacy and safety evaluations. Effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and quality of life (QOL) were recorded during the course of the trial. Results: Blood pressure reduction (BP) to the desired goals was observed with both the treatments. The SBP and DBP reductions were superior in triple combination therapy than double combination. Both treatments improved QOL of patients. Conclusion: Triple drug combination of telmisartan, amlodipine and HCT may serve a potential role in achieving desired BP goals, in patients with essential hypertension, which are otherwise poorly managed by either monotherapy or dual drug therapy. 展开更多
关键词 Essential HYPERTENSION telmisartan AMLODIPINE and HCT
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Application Effect Evaluation of Telmisartan combined with Spironolactone after Catheter Ablation of Patients with Paroxysmal Atrial Fibrillation
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作者 Rongcheng Zhao Jia Han Lei Zhao 《Journal of Clinical and Nursing Research》 2021年第3期135-139,共5页
Objective:To evaluate the application effect of telmisartan combined with spironolactone after catheter ablation of patients with paroxysmal atrial fibrillation.Methods:80 cases of patients with paroxysmal atrial fibr... Objective:To evaluate the application effect of telmisartan combined with spironolactone after catheter ablation of patients with paroxysmal atrial fibrillation.Methods:80 cases of patients with paroxysmal atrial fibrillation who received radiofrequency catheter ablation treatment from March 2013 to March 2016 in our hospital were randomly selected,these patients were divided into two groups according to the treatment methods,namely,the telmisartan with Spironolactone treatment group(combined treatment group,n=40)and the conventional therapy group(n=40).The hs-CRP,NT-proBNP,LAD and recurrence of the two groups were analyzed.Results:The hs-CRP,NT-proBNP levels after 3 months of the combined treatment group were significantly lower(P<0.05),the recurrence rate 10.0%(4/40)was significantly lower than the conventional therapy group 27.5%(11/40)(P<0.05),the time to recurrence was significantly longer than the conventional therapy group(P<0.05).Conclusion:The application effects of telmisartan combined with spironolactone after catheter ablation in the treatment of patients with paroxysmal atrial fibrillation are better than conventional therapy. 展开更多
关键词 Paroxysmal atrial fibrillation Catheter ablation telmisartan combined with spironolactone Application effect
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