共查询到18条相似文献,搜索用时 171 毫秒
1.
羟苯磺酸钙对2型糖尿病大鼠肾脏的保护作用 总被引:3,自引:2,他引:3
目的探讨羟苯磺酸钙对2型糖尿病大鼠肾脏的保护作用及其可能机制。方法以高糖高脂饮食联合低剂量链脲佐菌素(STZ)注射方法制作2型糖尿病动物模型。将SD大鼠分为对照组、模型组和实验组,实验组将羟苯磺酸钙溶于纯化水按100 mg·kg-1给大鼠灌胃,qd;对照组及模型组给予同等剂量的纯化水。6个月后进行肾脏形态学和生化指标的检测,用放免法检测血清、肾组织内皮素(ET)的水平,用免疫组织化学方法测量肾组织局部转化生长因子β1(TGF-β1)的表达。结果实验组大鼠的肾功能及肾脏病变明显改善;血清和肾组织ET水平降低;肾组织局部TGF-β1的表达减少。结论羟苯磺酸钙对2型糖尿病大鼠的肾脏有保护作用,其机制可能与降低肾组织ET和TGF-β1水平有关。 相似文献
2.
《药学学报》2009,44(4):344-349
为研究丙泊酚对实验性脑出血大鼠的脑保护作用,本研究采用左侧尾状核注射胶原酶0.5 U (1 U·μL-1) 诱导大鼠脑出血模型,并在胶原酶注射前10 min腹腔注射给予丙泊酚。观察丙泊酚对大鼠脑出血后神经行为学评分,脑含水量,脑组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及caspase-3表达的影响。结果显示,与脑出血组大鼠相比,丙泊酚(30和100 mg·kg-1)可不同程度地减小脑出血大鼠神经行为学评分(P < 0.05,P < 0.01),降低脑组织含水量(P < 0.05),提高脑组织SOD活性(P < 0.05),降低脑组织MDA含量(P < 0.01)。丙泊酚(15,30及100 mg·kg-1)可呈剂量依赖性地抑制caspase-3的表达(r = 0.877)。提示丙泊酚对大鼠脑出血损伤具有一定的保护作用,其机制可能与丙泊酚的抗氧化特性有关。
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3.
黄连碱对慢性肾功能衰竭大鼠的治疗作用及其机制研究 总被引:1,自引:1,他引:0
目的 探讨黄连碱对慢性肾功能衰竭(chronic renal failure,CRF)大鼠的治疗作用及其机制。方法 60只健康SD大鼠,♂,随机分为空白组、模型组、尿毒清组、黄连碱200,100和50 mg·kg-1剂量组,每组10只。除空白组外,各组大鼠灌胃腺嘌吟,连续28 d,制成CRF模型。造模同时,黄连碱200,100和50 mg·kg-1剂量组每日分别灌胃200,100和50 mg·kg-1黄连碱。治疗后,观察各组大鼠体质量的变化、检测24 h尿量及尿蛋白含量,Elisa法检测各组大鼠血清尿素氮(BUN)、肌酐(SCr)、TGF-β1及PAI-1的含量水平、Western blot法检测大鼠肾组织TGF-β1及PAI-1蛋白的表达。结果 与模型组比较,200,100和50 mg·kg-1剂量的黄连碱干预后,大鼠体质量及24 h尿量显著增加(P<0.05),尿蛋白显著降低(P<0.05),且血清中BUN、SCr、TGF-β1及PAI-1含量和肾组织TGF-β1和PAI-1表达均显著降低(P <0.05)。结论 黄连碱对CRF大鼠的肾功有一定的改善作用,其机制与降低血清及肾组织中TGF-β1和PAI-1表达有关。 相似文献
4.
羟苯磺酸钙对慢性肾衰模型大鼠血管活性物质的影响 总被引:5,自引:1,他引:5
目的:观察并探讨羟苯磺酸钙对慢性肾衰模型大鼠肾脏局部血管活性物质的影响及其作用机制。方法:将大鼠随机分为假手术组、模型组和羟苯磺酸钙治疗组,除假手术组外,其余2组行肾切除术建立肾衰模型,1wk后3组分别饮用水或羟苯磺酸钙灌胃,观察各组大鼠肾功能、肾脏局部血管活性物质含量及残肾组织病理的改变。结果:与模型组比较,羟苯磺酸钙组大鼠尿蛋白减少,肾功能改善,肾脏皮质匀浆中血栓素A2含量显著减少,残肾组织病理改变明显减轻。结论:羟苯磺酸钙可能通过降低肾衰模型大鼠肾脏局部血栓素A2含量而发挥肾脏保护作用。 相似文献
5.
苯那普利对糖尿病大鼠肾脏细胞凋亡的影响 总被引:5,自引:0,他引:5
目的探讨血管紧张素转换酶抑制剂(ACEI)苯那普利对糖尿病大鼠肾脏细胞凋亡及凋亡相关基因表达的影响。方法单侧肾切除大鼠ip STZ诱发糖尿病模型,每日ig苯那普利(10 mg·kg-1),共12周。采用原位末端标记法检测肾脏细胞凋亡情况,流式细胞术和免疫组化检测肾皮质凋亡相关基因Fas和Fas-L的表达。结果糖尿病组较对照组肾小球、肾小管凋亡细胞数明显增多,Fas和Fas-L的表达亦显著增强;苯那普利治疗组较糖尿病组凋亡细胞数减少,Fas和Fas-L的表达减弱。结论苯那普利可能通过影响凋亡相关基因Fas和Fas-L的表达而抑制肾脏细胞凋亡,从而发挥肾脏保护作用。 相似文献
6.
目的 介绍大鼠及小鼠 Pig-a基因突变试验方法,并汇总国家药物安全评价监测中心 2015—2022年开展的基于免疫磁珠检测法的大鼠及小鼠 Pig-a 基因突变试验背景数据。方法 阴性物质包括超纯水和 0.5% 羧甲基纤维素钠(CMCNa),雄性 C57BL/6J 小鼠间隔 24 h ig 0.5% CMC-Na,连续 7 d;雄性 SD 大鼠间隔 24 h ig 0.5% CMC-Na,连续 14 d;大鼠间隔24 h ig 超纯水,连续 3 d。阳性对照为已知致细菌突变化合物,包括 N-乙基-N-亚硝基脲(ENU,10、40 mg·kg-1)、盐酸丙卡巴肼(PCZ,60、150 mg·kg-1)、乌拉坦(EC,300、800 mg·kg-1)、N- 亚硝基二甲胺(NDMA ,1.5 mg·kg-1)、N- 亚硝基二乙胺(NDEA,15 mg·kg-1)。小鼠间隔 24 h ig ENU 40 mg·kg-1,连续 3 d;间隔 24 h ig NDMA 1.5 mg·kg-1、NDEA 15 mg·kg-1,连续 7 d。大鼠间隔 24 h ig PCZ 150 mg·kg-1、EC 800 mg·kg-1、ENU 40 mg·kg-1,连续 3 d ;间隔 24 h ig PCZ 60 mg·kg-1、EC300 mg·kg-1、ENU 10 mg·kg-1,连续28 d。分别于给予受试物前,首次给予后14、28 d采集外周血,用流式细胞术检测大鼠红细胞表面 CD59蛋白的结合情况,结合免疫磁性计数微球技术计算网织红细胞(RETs)占总红细胞的百分率(%RET)(作为外周血毒性考察指标)、总红细胞中CD59表达为阴性细胞(RBCCD59-,即突变的总红细胞)发生率和RETs中CD59表达为阴性细胞(RETCD59-,即突变的 RETs)发生率。结果 各试验%RET数值均无大幅增加。SD大鼠和 C57BL/6J 小鼠的阴性对照组RBCCD59-和 RETCD59-突变率均低于 5×10-6,小鼠的背景值相对不稳定。连续 3 d ig给予小鼠 40 mg·kg-1的 ENU,RBCCD59-和RETCD59-发生率自给药后2周开始均大幅增加(P<0.05),给药后4周进一步增加(P<0.01、0.001);给予小鼠NDMA后2、4周,RBCCD59-发生率略有增加,但仍在阴性背景范围内,但RETCD59-发生率在给药后第2周大幅增加(P<0.001),给药后第4周则大幅回落;给予小鼠NDEA后2周,RBCCD59-和RETCD59-发生率均有所增加(P<0.05、0.001),给药后第 4 周则有所降低。连续3 d ig给予大鼠40 mg·kg-1 ENU,或连续28 d ig给予大鼠10 mg·kg-1 ENU,RBCCD59-、RETCD59-发生率自给药后第2周开始均大幅增加(P<0.001),给药后第 4 周进一步增加(P<0.001);连续 3、28 d ig 给予大鼠不同剂量的 PCZ 或 EC 后,RBCCD59-和RETCD59-发生率的变化趋势与 ENU类似,但 EC诱发的突变细胞率低于 ENU和 PCZ。结论 体内 Pig-a基因突变试验可在首次给药后4周内有效检出致细菌突变化合物ENU、PCZ、EC、NDMA、NDEA的致突变性。提供了大鼠和小鼠Pig-a基因突变试验的背景值范围,为标准化试验方法的建立和研究结果的判定提供借鉴。 相似文献
7.
藏药旺拉提取物对东莨菪碱致动物学习记忆障碍的改善作用及机制研究 总被引:1,自引:0,他引:1
《药学学报》2009,44(5):468-472
观察藏药旺拉提取物(CE)对东莨菪碱致动物学习记忆障碍的改善作用并研究其作用机制。采用腹腔注射东莨菪碱造模,以跳台法测定小鼠的学习记忆能力,以电生理方法测定大鼠海马长时程增强(LTP)的诱导, 分别以生化及放射性同位素分析法测定脑匀浆中乙酰胆碱酯酶(AChE)及胆碱乙酰转移酶(ChAT)的活性。结果表明,模型动物跳下平台的潜伏期明显缩短,LTP诱导受抑制。灌胃给予CE(5、10及20 mg·kg-1)可改善模型小鼠在跳台中的表现,腹腔注射CE(5 mg·kg-1)可逆转东莨菪碱对大鼠LTP诱导的抑制。此外,CE可显著增强ChAT活性,而对AChE活性无显著影响。CE可改善东莨菪碱致小鼠学习记忆障碍,其作用可能与改善海马LTP诱导及增强ChAT活性有关。
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8.
目的 探究泽泻多糖对糖尿病大鼠肾损伤的改善作用。方法 SPF级SD雄性大鼠随机分为对照组,模型组,吡格列酮[过氧化物酶体增殖物激活受体γ(PPAR-γ)激活剂,20 mg·kg-1]组,泽泻多糖低、中、高剂量(100、200、400 mg·kg-1)组和泽泻多糖(400 mg·kg-1)+ GW9662(PPAR-γ抑制剂,10 mg·kg-1)组,除对照组外均采用高糖高脂+链脲佐菌素(STZ)柠檬酸钠缓冲液法制备糖尿病肾病(DN)大鼠模型,造模后各组ig给药,每天1次,连续6周。血糖仪测定大鼠空腹血糖(FBG)水平;全自动生化分析仪检测大鼠血清肌酐、尿酸、尿素氮水平,检测24 h尿蛋白及尿肌酐,计算内生肌酐清除率(Ccr);处死大鼠,计算大鼠肾脏指数;HE染色观察大鼠右侧肾脏组织病理学变化;Western blotting法检测肾脏组织PPAR-γ/肝X受体-α(LXR-α)/ATP结合盒转运蛋白G1(ABCG1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)蛋白水平。结果 与对照组比较,模型组大鼠毛色枯黄,体质量显著减轻(P<0.05);肾小球细胞空泡化、肾小球基底膜增厚;肾脏指数、FBG、24 h尿蛋白、尿酸、尿素氮、TNF-α和IL-1β蛋白水平显著升高(P<0.05),Ccr和PPAR-γ、LXR-α、ABCG1蛋白水平显著降低(P<0.05);与模型组比较,吡格列酮组和中、高剂量泽泻多糖组大鼠毛色及饮食、饮水逐渐恢复,体质量显著增加(P<0.05);肾损伤程度减轻;FBG、24 h尿蛋白、尿酸、TNF-α和IL-1β蛋白水平显著降低(P<0.05),Ccr及PPAR-γ、LXR-α、ABCG1蛋白水平显著升高(P<0.05);泽泻多糖高剂量组肾脏指数显著降低(P<0.05)。高剂量泽泻多糖组与吡格列酮组各指标差异比较无统计学意义,GW9662可逆转高剂量泽泻多糖对大鼠肾脏功能的保护作用。结论 泽泻多糖可能通过激活PPAR-γ/LXR-α/ABCG1通路保护DN大鼠肾脏。 相似文献
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氯沙坦对糖尿病大鼠肾皮质血管紧张素Ⅱ2型受体及诱生型一氧化氮合酶基因表达的影响 总被引:1,自引:0,他引:1
目的 研究氯沙坦对糖尿病大鼠肾组织血管紧张素系统与一氧化氮系统的影响及其二者之间的关系。方法 SD大鼠随机分成3组:对照组、糖尿病组和氯沙坦(30 mg·kg-1·d-1×8周, ig)治疗组。应用RT-PCR技术检测大鼠肾皮质血管紧张素Ⅱ2型受体(AT2)、Ⅳ型胶原及诱生型一氧化氮合酶(iNOS)mRNA表达。并同时检测大鼠肾皮质血管紧张素Ⅱ(AngⅡ)、NO含量及一氧化氮合酶(NOS)活性。结果 糖尿病组大鼠尿蛋白排泄率、肾皮质AngII含量、Ⅳ型胶原mRNA及iNOS mRNA表达较对照组明显升高;糖尿病大鼠肾皮质NOS活性也较对照组明显增强;然而糖尿病大鼠肾皮质NO含量及AT2 mRNA水平却较对照组大鼠明显降低;氯沙坦治疗能显著降低糖尿病大鼠尿蛋白排泄率及肾皮质Ⅳ型胶原mRNA表达;并能明显增加肾皮质AT2及iNOS mRNA表达及总NOS活性及NO含量。结论 AT2的激活与氯沙坦的肾脏保护作用有关,并可能参与了对肾脏iNOS mRNA表达的上调。 相似文献
10.
目的 研究大黄-丹参药对对慢性肾衰竭(CRF)模型大鼠结肠黏液屏障功能的影响。方法 70只雄性Wistar大鼠随机分为假手术组、模型组、尿毒清颗粒组(2.5 g·kg-1)和大黄-丹参药对高、低剂量组(生药6.0、3.0 g·kg-1),每组14只。除假手术组外,其余各组大鼠采用5/6肾切除法制备CRF模型。连续ig给药12周后,腹主动脉取血测定血清肌酐(Scr)、尿素氮(BUN)、白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)水平;剖取残存肾脏和结肠组织,HE和Masson染色观察大鼠肾组织形态学和纤维化改变;阿利新蓝-过碘酸-雪夫(AB-PAS)染色观察结肠黏液层厚度和杯状细胞数量变化;免疫组化观察大鼠结肠组织黏蛋白2(Muc2)阳性表达;采用实时荧光定量(qRT-PCR)法和蛋白免疫印记(Westernblotting)法检测大鼠结肠组织Muc2的mRNA和蛋白表达情况。结果 与假手术组相比,模型组大鼠血清Scr、BUN、IL-1β、IL-6和TNF-α水平明显升高(P<0.01);肾组织中肾小球硬化、肾小管扩张,肾间质可见炎性细胞浸润和纤维化,纤维化评分显著增加(P<0.01);结肠黏液层变薄,杯状细胞减少;结肠组织Muc2阳性表达降低,结肠组织Muc2的mRNA和蛋白表达水平均降低(P<0.01)。与模型组比较,大黄-丹参药对高、低剂量组能显著降低模型大鼠血清Scr、BUN、IL-1β、IL-6和TNF-α水平(P<0.01);肾组织形态明显改善,肾纤维化评分显著降低(P<0.01);结肠黏液层厚度增加,杯状细胞增多;结肠组织Muc2阳性表达升高,结肠组织Muc2的mRNA和蛋白表达水平明显升高(P<0.01)。结论 大黄-丹参药对能够有效保护CRF大鼠的残存肾功能,延缓CRF进展;其机制可能与恢复CRF大鼠结肠黏液屏障功能,改善机体炎症状态有关。 相似文献
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在心肌缺血/再灌注 (MI/R) 时, 一氧化氮 (NO) 生成量减少, 氧自由基 (ROS) 大量堆积, 均可加重MI/R损伤。据此设计合成了可同时释放NO的ROS清除剂——乙酰阿魏单硝酸异山梨醇酯 (AFI), 并研究了AFI对MI/R大鼠的心肌保护作用及其作用机制。建立常规大鼠MI/R (30 min/3 h) 模型, 随机给予AFI (10 mg·kg-1)、阿魏酸 (40 mg·kg-1) 或单硝酸异山梨酯 (30 mg·kg-1) 药物治疗 (ig), 再灌注末检测大鼠心肌梗死面积和心功能指标, 同时测定血清肌酸激酶、乳酸脱氢酶、超氧化物歧化酶活性、过氧化氢与丙二醛水平及NO含量。与阿魏酸钠、单硝酸异山梨醇单独治疗组或联合治疗组相比, AFI治疗组心肌梗死面积显著减小 (n = 8, P < 0.01), 左室发展压、左室等容收缩/舒张期压力上升或下降最大速率显著提高 (n = 8, P < 0.05), 血清肌酸激酶和乳酸脱氢酶活性显著降低。与阿魏酸钠或单硝酸异山梨醇单独治疗组相比, AFI治疗组血清超氧化物歧化酶活性增加、过氧化氢与丙二醛含量降低而NO含量显著升高 (n = 8, P均< 0.05)。这些结果表明, AFI这一新化合物可减轻大鼠MI/R损伤, 具有保护心脏功能, 其心肌保护作用比阿魏酸钠、单硝酸异山梨醇的单独使用或联合使用均强。 相似文献
12.
《药学学报》2009,44(5):558-560
This study is to investigate therapeutic effect of astaxanthin on acetic acid-induced gastric ulcer in rats. Rats were divided into control group, ulcer control group, and astaxanthin (5, 10, and 25 mg·kg-1) groups at random, 8 rats in each group. After administered for 10 days consecutively, all the rats were sacrificed. The area of ulcer and the levels of MDA, SOD, CAT and GSH-Px in gastric mucosa were measured. Compared with ulcer control group, in astaxanthin (5, 10, and 25 mg·kg-1) groups, the area of ulcer was decreased significantly. Level of MDA decreased while activities of SOD, CAT and GSH-Px increased (P < 0.05). Astaxanthin has good therapeutic effect on acetic acid-induced gastric ulcer in rats. Eliminating free radical and improving local blood circulation of the ulcer may be the mechanism of action. 相似文献
13.
观察力达霉素 (LDM)、LDM与甲氨蝶呤 (MTX) 联合用药对人纤维肉瘤HT-1080LUC实验性肺转移的抑制作用。构建稳定表达荧光素酶的HT-1080细胞株并扩增培养, 检测HT-1080LUC细胞的荧光素酶的表达。建立裸鼠人纤维肉瘤HT-1080LUC实验性肺转移模型, 并采用活体动物成像系统监测肿瘤的生长情况, 观察LDM和MTX的体内抗肺转移瘤活性。结果表明, HT-1080LUC细胞荧光光子量与细胞数呈线性相关, 最小可检测的细胞数量为100个/孔。活体成像结果显示, 治疗组裸鼠的肺部荧光强度较对照组明显减弱。单独给予LDM 0.025 mg·kg−1、LDM 0.05 mg·kg−1或MTX 0.5 mg·kg−1的肺转移抑制率分别为53.9%、75.9%和70.2%; LDM 0.025 mg·kg−1与MTX 0.5 mg·kg−1联合应用的肺转移抑制率为88.7%, 两药相互作用指数CDI = 0.82。研究表明, LDM对人纤维肉瘤肺转移有明显抑制作用, 与MTX联合用药对肺转移瘤的疗效明显优于单独给药。 相似文献
14.
Françoise Chollet-Debord Nicole Moins Pierre Gachon Pierre Duchene-Marullaz 《Naunyn-Schmiedeberg's archives of pharmacology》1986,334(1):105-109
Summary Verapamil and bepridil share the common property of antagonizing the slow inward calcium-mediated current, but bepridil has some additional antiarrhythmic properties. The efficacy of these two compounds against CaCl2-induced arrhythmias has been compared in rats. CaCl2 was administered i.v. by continuous infusion until death (25 mg·kg–1·min–1 or 40 mg·kg–1·min–1) or by bolus injection (160 mg·kg–1). Bepridil (5, 10 mg·kg–1) or verapamil (2.5,5 mg·kg–1) were injected 10 min before CaCl2. Bepridil (10 mg·kg–1) or verapamil (5 mg·kg–1) prolong the survival time during CaCl2 infusion. After pretreatment, the injection of 160 mg·kg–1 CaCl2 is less toxic: 25% of animals are protected by bepridil (5 mg·kg–1), 41% by bepridil (10 mg·kg–1) or verapamil (5 mg·kg–1).At death the myocardial Ca2+ level is not different in controls and pretreated animals, thus, the ratio myocardial Ca2+/total injected Ca2+ is significantly lowered by bepridil (10 mg·kg–1) or verapamil (5 mg·kg–1). The efficacy of the two drugs on this model appears related solely to inhibition of slow inward current despite the additional antiarrhythmic profile of bepridil. 相似文献
15.
T. M. Garrigues U. Martin J. E. Peris-Ribera L. F. Prescott 《European journal of clinical pharmacology》1991,41(2):179-183
Summary The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg · kg–1.As the dose of cefadroxil increased from 5 to 15 and 30 mg · kg–1, the peak plasma concentrations, normalized to 5 mg · kg–1, decreased significantly from 15.1 to 10.7 and 7.6 mg·l–1, while the corresponding normalized areas under the plasma concentration-time curves from 0 to 2 h decreased significantly from 1258 to 946 and 801 min·mg·l–1.When the same subjects were given 5 mg·kg–1 of cefadroxil together with 45 mg·kg–1 of cephalexin, the absorption of cefadroxil was slowed to a similar or greater extent than with the high dose of cefadroxil.Although the absorption rate decreased as the dose increased, the systemic availability of cefadroxil was essentially complete at all doses, as judged by the 24 h urinary recoveries of the antibiotic. Kinetic analysis of the plasma concentration-time curves gave the best fit with a zero-order followed by a first-order absorption process, consistent with saturable intestinal absorption of cefadroxil.The elimination rate of cefadroxil was directly related to dose and plasma concentrations, and the clearance at the dose of 5 mg·kg–1 was significantly increased by the simultaneous administration of high-dose cephalexin.The renal clearance of cefadroxil ranged from 98 ml·min·l–1 at total plasma cephalosporin (cefadroxil + cephalexin) concentrations less than 2.5 mg·l–1 to 156 mg·l–1 at concentrations greater than 40 mg·l–1. These findings are consistent with saturable active gastrointestinal absorption and renal tubular reabsorption of cefadroxil, with competitive inhibition of both processes by cephalexin. 相似文献
16.
Marie-Hélène Thiébot Joseph Kloczko Raymond Chermat Pierre Simon Philippe Soubrié 《Psychopharmacology》1980,67(1):91-95
The stimulant effects of oxolinic acid were investigated in rats and mice. This drug, given orally, consistantly induced, in doses ranging from 16 to 256 mg·kg-1, locomotor stimulation and stereotyped behavior.These effects were antagonized by pimozide (1 mg·kg-1), -methyltyrosine (64 mg·kg-1) or reserpine (4 mg·kg-1, 24 h before testing) pretreatment, suggesting a facilitatory role of oxolinic acid on catecholaminergic processes.Diazepam (4–16 mg·kg-1) reduced the stimulant effects induced by oxolinic acid but not those induced by amphetamine; oxolinic acid (8 mg·kg-1) markedly reduced the antipunishment effect elicited in rats by diazepam (2 mg·kg-1). Since benzodiazepines have been reported to enhance GABA functioning, these data suggest that oxolinic acid may impair GABA transmission. However, neither muscimol (0.5–1 mg·kg-1) or -acetylenic-GABA (16–64 mg·kg-1) selectively reduced the stimulant effects elicited by oxolinic acid. Therefore, the possible facilitation exerted by this drug on catecholaminergic systems may not derive from the release of an inhibitory GABAergic control. 相似文献
17.
Summary We have investigated the interaction of -monofluoromethyldopa (MFMD) with the effects of i.p. injectedl-DOPA (200 mg·kg–1) on blood pressure and tissue catecholamines in normal and spontaneously hypertensive rats (SHR). MFMD 10 mg·kg–1 (i.p.) effectively antagonizes thel-DOPA induced increase in heart dopamine (DA). This action is also seen after 15 or 50 mg·kg–1. The accumulation of DA in the brain is very much reduced by MFMD 50 mg ·kg–1 while after 15 or, especially, 10 mg·kg–1 more DA is formed in the rrain than afterl-DOPA alone, probably due to the peripheral decarboxylase inhibition which presents morel-DOPA to the brain. We conclude that MFMD 10 mg ·kg–1 gives a relatively selective peripheral inhibition of the decarboxylation ofl-DOPA and this dose combination was accordingly found to result in a reduction of blood pressure in conscious animals. This hypotensive response tol-DOPA was attenuated after MFMD 15 mg·kg–1 and was absent after MFMD 50 mg·kg–1. Interestingly, the hypotensive effect ofl-DOPA after MFMD 10 or 15 mg·kg–1 was more pronounced in SHR. 相似文献
18.
Dose-dependent pharmacokinetics of benzoic acid following oral administration of sodium benzoate to humans 总被引:2,自引:0,他引:2
Summary Plasma concentration-time data for benzoic and hippuric acids and urinary excretion-time data for hippuric acid were analyzed simultaneously after oral doses of 40, 80 or 160 mg/kg sodium benzoate administered at least one week apart to 6 healthy subjects.The mean AUCs of benzoic acid after the doses of 80 and 160 mg/kg of sodium benzoate were 3.7- and 12.0-times greater, respectively, than after 40 mg/kg. However, the mean AUC of hippuric acid was roughly proportional to the benzoate doses. The observed data were explained by a one-compartment model with first-order rate absorption and Michaelis-Menten elimination of benzoic acid, together with a one-compartment model with first-order elimination for hippuric acid.Although the maximum rate of biotransformation of benzoic acid to hippuric acid varied between 17.2 and 28.8 mg·kg–1·h–1 among the six individuals, the mean value (23.0 mg·kg–1·h–1) was fairly close to that provided by daily maximum dose (0.5 g·kg–1·day–1) recommended in the treatment of hyperammonaemia in patients with inborn errors of ureagenesis.The individual maximum rate of metabolism can be estimated from the urinary excretion rate of hippuric acid 1.5 to 3 h after the single oral dose of 80 to 160 mg·kg–1 sodium benzoate. The justification of this concept requires further studies in patients with inborn errors of urea synthesis.This study was supported in part by a grant-in-aid from the Ministry of Human Health and Welfare, Tokyo, Japan 相似文献