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Protective Effects Of Total Alkaloids In Corydalis Saxicola Bunting On Liver Injuries And Meta-analysis Of Telmisartan On Blood Pressure Control

Posted on:2010-07-01Degree:MasterType:Thesis
Country:ChinaCandidate:G L XiFull Text:PDF
GTID:2144360275975711Subject:Health Toxicology
Abstract/Summary:PDF Full Text Request
PART ONE: Protective effects of total alkaloids in Corydalis Saxicola Bunting on liver injuriesObjective: To investigate the preventive and curative effects of total alkaloids in Corydalis Saxicola Bunting (CSBTA) on acute and chronic liver injuries in rats induced by different hepatotoxicity agents. Methods: 10 % D-Galactosamine hydrochloride 500 mg/kg intraperitoneal injection, 1.1 % phenyl-isothiocyanate 10 ml/kg intragastric administration, and 25 % carbon tetrachloride (CCl4) 2 ml/kg subcutaneous injections (sc) were used to induce acute liver injuries of rats, and the rats were treated with CSBTA at doses of 20, 60, 120 mg/kg, which were given once daily for 1 week. Then, 25 % CCl4 2 ml/kg sc one time a week was used to induce chronic hepatic fibrosis, and the rats were treated with CSBTA at doses of 20, 40, 80 mg/kg, which were given once a day for 8 weeks. Following CSBTA treatment, blood was collected from the rat abdominal aorta and serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) etc. were detected. The livers were obtained for histopathologic examination, and hydroxyproline (HYP) analysis was investigated in hepatic fibrosis liver. Results: Pre-treated with CSBTA dose-dependently decreased the elevated level of ALT, AST and ALP induced by D-Galactosamine hydrochloride, phenyl-isothiocyanate and CCl4. Pathological scores of the liver in pre-treated rats were lower than acute liver injury rats without CSBTA treatment. Serum ALT, AST and ALP levels were found to be elevated in rats with liver fibrosis. However, treatment with CSBTA resulted in reversing the elevated serum enzymes induced by CCl4. Serum total protein and albumin levels were elevated in CSBTA group when compared to liver fibrosis rats without CSBTA treatment. Hepatic level of HYP and pathological score were also significantly attenuated by CSBTA treatment in hepatic fibrosis rats. Conclution: CSBTA showed significant preventive effects on acute liver injury in rats induced by D-Galactosamine hydrochloride, phenyl-isothiocyanate and CCl4. Moreover, in CCl4 induced hepatic fibrosis rats, CSBTA could ameliorate the liver damage and relieve the development of hepatic fibrosis. PART TWO: Meta-analysis of telmisartan on blood pressure controlObjective: To evaluate the efficacy and tolerability of telmisartan compared with losartan on blood pressure (BP) control. Methods: Pertinent studies were selected through extensive searches of PubMed (1966 - 29 December 2007), Embase (1980 - 29 December 2007), and the Cochrane library (29 December 2007). Randomized clinical trials comparing telmisartan with losartan in patients with hypertension were selected by predefined criteria. The data of included literatures were extracted and the study quality was assessed by two authors independently. The main efficacy measures included diastolic and systolic BP (DBP and SBP) reduction, and therapeutic DBP and SBP response. The pooled estimates were carried out in RevMan version 5.0 software. Sensitivity analysis and publication bias evaluation were also carried out. Results: We reviewed the full text of 24 articles from 429 studies identified from our initial literature search and hand search. A total of eleven randomized controlled trials met criteria for inclusion in the present meta-analysis. Ten trials of 1792 patients reported clinic BP reduction; six trials of 1163 patients reported ambulatory BP reduction; seven trials of 1675 patients reported therapeutic BP response. On the basis of Jadad scale, seven papers are high-quality studies, while the others are low-quality studies. Funnel plots indicated that one trial (Fang&Lin trial) had true heterogeneity. Use of telmisartan resulted a significant reduction in clinic DBP (weighted mean difference 2.69, 95% confidence interval 1.03 to 4.34) and SBP (2.76, 1.90 to 3.63) compared with losartan. When excluding the Fang&Lin trial, there was also a significant reduction in clinic DBP (1.52, 0.85 to 2.19) and SBP (2.81, 1.93 to 3.69) comparing telmisartan with losartan. There was also a significant reduction in full 24-h mean ambulatory DBP (3.96, 0.48 to 7.45) and SBP (2.47, 0.40 to 4.55) comparing telmisartan with losartan. Significant increase in therapeutic DBP (relative risk 1.14, 1.04 to 1.23) and SBP (1.14, 1.05 to 1.24) response with telmisartan compared to losartan was also found. When excluding the trials with low qualify, there was also a significant reduction in DBP and a significant increase in therapeutic DBP response comparing telmisartan with losartan. Both telmisartan and losartan were well tolerated. Conclution: Compared with losartan, telmisartan provides superior control of blood pressure and has no association with increased risks of adverse events.
Keywords/Search Tags:Corydalis Saxicola Bunting, alkaloids, pharmacodynamics, liver injury, chronic hepatic fibrosis, telmisartan, losartan, hypertension, meta-analysis
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