盐酸纳洛酮舌下含片在犬体内的药代动力学及绝对生物利用度

本文采用高效液相色谱－电化学检测法研究了盐酸纳洛酮舌下含片在犬体内的药代动力学及绝对生物利用度。雄性犬８只，ｉｖ５ｍｇ盐酸纳洛酮后，血浆药物浓度的经时过程符合二室开放模型，分布半衰期（ｔ１／２α）为１２．０ｍｉｎ，消除半衰期（ｔ１／２β）为１４３．４ｍｉｎ，ＡＵＣ为７．９２ｍｇ（ｍｉｎ／Ｌ。犬给予５ｍｇ盐酸纳洛酮舌下含片后，血浆药物浓度的经时过程符合一级吸收二室开放模型，吸收较快，吸收半衰期（ｔ１／２Ｋａ）为１１．０ｍｉｎ，分布半衰期（ｔ１／２α）为１５．４ｍｉｎ，消除半衰期（ｔ１／２β）为１６４．１ｍｉｎ，达峰时间（Ｔｍａｘ）为２７．７ｍｉｎ，高峰浓度（Ｃｍａｘ）为３４．２ｎｇ／ｍｌ，ＡＵＣ为６．７９ｍｇ．ｍｉｎ／Ｌ，盐酸纳洛酮舌下含片的绝对生物利用度为８６．８（１０．９％。经统计学检验，两种途径给药后的ｔ１／２α、ｔ１／２β、（和（均无显著性差异（Ｐ＞０．０５）。上述结果表明，盐酸纳洛酮舌下含片在犬体内的处置过程与ｉｖ途径是相似的，生物利用度较高，预计在临床能产生较好的疗效     

~(19)F体内核磁共振技术观测5-氟尿嘧啶在小鼠植入肿瘤中的摄取与代谢

应用体内１９ＦＮＭＲ谱观察并定量评价了５－氟尿嘧啶（５－ＦＵ）在荷Ｓ１８０瘤和Ｂ１６瘤小鼠肿瘤内的摄取和代谢动力学过程．５－ＦＵ２００ｍｇ·ｋｇ－１ｉｖ后，药物在Ｓ１８０和Ｂ１６瘤内的主要产物为其活性产物氟代核苷／核苷酸（ＦＮＵＣ），同时可检测到少量的降解产物α－氟－β－丙氨酸（ＦＢＡＬ）和α－氟－β－脲基丙酸（ＦＵＰＡ）．在Ｓ１８０瘤内，５－ＦＵ摄取，消除以及ＦＮＵＣ的生成有较大的个体变异，５－ＦＵ的消除半衰期ｔ１／２ｋｅ为４１．５－８４．８ｍｉｎ，ＦＮＵＣ生成ｔ１／２ｒ为２６．０－９１．９ｍｉｎ．当甲氨蝶呤（ＭＴＸ）与５－ＦＵ合用时，５－ＦＵ在Ｓ１８０瘤内的活化代谢过程明显加快，ｔ１／２ｋｅ缩短为２９．９－４３．４ｍｉｎ，ＦＮＵＣ的生成速率显著提高，生成量增加．５－ＦＵ在Ｂ１６瘤内的摄取及代谢过程的个体波动较小，其ｔ１／２ｋｅ为３９±５ｍｉｎ，ＦＮＵＣ的生成ｔ１／２ｒ为６０±７ｍｉｎ，在Ｂ１６瘤内，ＭＴＸ的合用不能明显加快５－ＦＵ转化为ＦＮＵＣ的反应，也不改变５－ＦＵ在瘤内的消除模式．上述结果表明，５－ＦＵ对肿瘤的化疗作用与肿瘤灌注５－ＦＵ在瘤组织内的摄取和活化代谢过程密切相关，亦可受到合用药物的影响．     

重组葡激酶在大鼠体内的药物动力学研究

目的：研究重组葡激酶在大鼠体内的药物动力学。方法：采用氯胺Ｔ法标计１２５Ｉ重组葡激酶（放化纯度＞９８％）,给大鼠静注三种不同剂量后进行药物动力学试验,数据采用 ３ｐ８７程序按二室模型计算药动学参数。结果：ｔ１／２α约为０．９１３～１,３３６ｍｉｎ,ｔ１／２β约为２２．５１～２３．８９ｍｉｎ。５ｍｉｎ后各组织有较高放射量,以肾、脾、肝为最高。到１２０ｍｉｎ各组织只有很少的放射量。尿、胆汁在３ｈ内可明显测到放射性,２４ｈ内从尿中排出给药量的４２．８％放射量,从粪中排出 ７ ５％,在３３ｈ内从胆汁中排出给药量的 ９．４％放射量。 ＳｐｅＰＡＧＥ电泳结果表明,尿和胆汁中原形葡激酶甚微,排出物主要是分解产物。结论：１２５Ｉ－ｒ－Ｓａｋ静注,在大鼠体内分布快,分布广,消除快。     

甲基毒死蜱在大鼠体内的毒物代谢动力学

给大鼠ｉｖ１７１ｍｇ·ｋｇ￣（－１）或ｉｇ６８４ｍｇ·ｋｇ￣（－１）甲基毒死蜱（ＣＭ）后，血中ＣＭ浓度的经时变化符合二室开放模型和一级吸收二室开放模型，ＣＭ经消化递吸收相半减期为１３．２ｍｍ、吸收率（Ｆ）为１７％。ＣＭ在体内呈全身分布，ｉｖＣＭ后的ｔ１／２ａ为２ｍｉｎ，ｔ１／２β为１．７４ｈ，全身清除率为０．８６Ｌ·ｋｇ￣（－１）·ｈ￣（－１）．大鼠ｉｖ１７１ｍｇ·ｋｇ￣（－１）ＣＭ后，血，肾和辜丸中ＣＭ浓度的经时变化呈二项指数函数曲线规律，而在肺，肝，脾，心，脑，肌肉和脂肪中的变化则符合叠加指数函数规律。根据靶向指数。靶向系数和综合靶向系数判断，肺和脂肪是ＣＭ选择分布的主要部位。体外代谢研究表明。ＣＭ主要是在肝脏被代谢转化。肝细胞的可溶性胞浆和微粒体是主要的代谢转化场所。     

国产芬太尼在法洛四联症患儿的药代动力学研究

目的;探讨法洛四联症根治术患儿大剂量应用国产芬太尼的药代动力学。方法：随机选择法洛四联症根治术患儿８例,芬太尼１０μｇ／ｋｇ静注后用微量泵持续输注１μｇ／（ｋｇ．ｍｉｎ）至切皮,用ＧＣ－ＭＳ测定血浆芬太尼浓度,并计算药药动力参数。结果：芬太尼的药代动力学符合开放型三室模型,其快速分布半衰期（ｔ１／２π）,缓慢分地衰期（ｔ１／２α）和消除半衰期（ｔ１／２β）分别为１．３０,１１．０和３７３．５ｍｉｎ     

阿克拉霉素癌微囊的研究(英文)

研究工作阐述了毫微囊的制备及冻干条件，并进行了毫微囊的再分散性实验，测定了毫微囊的粒度分布和药物包封率。家兔静脉注射阿克拉霉素Ａ毫微囊后，血药浓度表明其符合二室开放模型，与阿克拉霉素Ａ注射液相比，阿克拉霉素Ａ毫微囊在家兔体内的消除半衰期较长，（前者ｔ１／２（β）＝１０．２５ｈ，Ａｕｃ＝８１．８８ｍｇ／Ｌ·ｈ；后者ｔ１／２（β）＝１７．０４ｈ，Ａｕｃ＝１０６．７４ｍｇ／Ｌ·ｈ），而且阿克拉霉素Ａ包于聚氰基丙烯酸正丁酯毫微囊后改变了其在大鼠体内的组织分布。结果表明：阿克拉霉素Ａ在肺、胸腺、脾和小肠中浓度较高，而在心、肾、肝和大肠中浓度较低。     

抑制肠道细菌丛和非特异性羧酸酯酶对T2毒素在原位灌流大鼠小肠袢中代谢的影响

预先用新霉素和头孢氨苄抑制肠道细菌丛后，Ｔ２毒素在灌流小肠袢内的代谢速度明显减慢，ｔ１／２β由正常的２６ｍｉｎ延长为１３１ｍｉｎ．主要代谢产物ＨＴ２的生成减少．Ｔ２毒素羟化生成３′－羟基ＨＴ２的反应被抑制．当Ｔ２毒素对预先用二异丙基氟磷酸酯抑制酯酶的小肠袢进行肠系膜一门脉血管灌流时．Ｔ２毒素的ｔ１／２β由正常的４７ｍｉｎ延长至１２０ｍｉｎ，ＨＴ２的生成部分被抑制，而３′－ＯＨＨＴ２的生成量显著增加．同时抑制肠道细菌丛和酯酶．Ｔ２毒素在小肠中的代谢转化基本被阻断．实验结果表明，Ｔ２毒素在大鼠小肠中的代谢转化反应主要在肠道细菌丛酶系统和非特异性羧酸酯酶的共同作用下进行．抑制肠道细菌丛酶系统可同时减少Ｔ２毒素在小肠中的水解和羟化反应．而抑制酯酶仅能减少水解反应．与此同时轻化产物增加．     

新型抗癌药MKT-077的药代动力学和抗癌疗效

ＭＫＴ－０７７为一种新的含硫花青染料类抗癌药物,它提供了一种新的抗癌机制,即在癌细胞（如结肠、乳腺、胰腺等）线粒体上聚集,使得作用在线粒体上的亲脂性离子化合物（ＤＬＣ）离域。本研究探讨了ＭＫＴ－０７７在ＢＤＦ１小鼠中的代谢和在荷瘤小鼠中的分布。　　药代动力学　ｉｖ［１４Ｃ］ＭＫＴ－０７７后,血浆中１４Ｃ水平符合三相模型。在第一个分布相,１４Ｃ的ｔ１／２约为５ｍｉｎ,在第二、第三相ｔ１／２分别为２．８～４．６ｈ（１．０～３．０ｍｇ·ｋｇ－１）和１６．２ｈ（３ｍｇ·ｋｇ－１）。ｃｍａｘ在０．３～１．…     

用HPLC测定血液透析病人头孢唑啉血药浓度

血液透析病人８例，在血透时及血透间期分别自血透导管和静脉注射头孢唑啉４ｇ，ＨＰＬＣ测定血清头孢唑啉浓度，按单室模型用二点法计算药物清除半衰期（ｔ１／２）分别为：６．７６±１．６２ｈ、４８．１±２１．５ｈ。血透间期给药后２４ｈ体内血药浓度为２４６．２±３０．２μｇ／ｍｌ，高于有效浓度十几倍。由于给药途径不同ｔ１／２明显差异。表明：４ｇ／ｄ给药剂量过高，应减量。     

抑制肠道细菌丛和非特异性羧酸酯酶对T2毒素在原位灌…

预先用新霉素和头孢氨苄抑制肠道细菌丛后，Ｔ２毒素在灌流小肠袢内的代谢速度明显减慢，ｔ１／２β由正常的２６ｍｉｎ延长为１３１ｍｉｎ。主要代谢产物ＨＴ２的生成减少，Ｔ２毒素羟化生成３＇－羟基ＨＴ２的反应被抑制。当Ｔ２毒素对预先用二异丙基氟磷酸酯抑制酯酶的小肠袢进行肠系膜－门脉血管灌流时，Ｔ２毒素的ｔ１／２β由正常的４７ｍｉｎ延长至１２０ｍｉｎ。ＴＨ２的生成部分被抑制，而３＇－ＯＨＨＴ２的生成量显著增加     

D-半乳糖导致小鼠骨丢失及其机制初探

目的　探讨D 半乳糖对小鼠骨代谢的影响及其可能机制。方法　 3mon龄昆明种♀小鼠每日颈背部皮下注射D 半乳糖 10 0 0mg·kg-1·d-1,连续 4 2d ,取右侧股骨测定骨干重、骨羟脯氨酸、骨钙、骨微量元素 ,同时检测抗氧化酶活性及脂质过氧化产物。结果　D 半乳糖可使骨干重、骨羟脯氨酸、骨钙减少 ,骨干重与体重比值 ,骨镁与骨干重比值降低 ;同时 ,抗氧化酶活性下降 ,脂质过氧化产物增加。结论　D 半乳糖可导致 3mon龄小鼠骨质丢失 ,其发生可能与骨镁减少及抗氧化酶活性降低有关     

羊栖菜多糖对L_(615)小鼠LPO含量及GR、GSH—PX、CAT和SOD活性的影向

本文报道了羊栖菜多糖(SFPS)对L_(615)小鼠全血及肝脾脂质过氧化物(LPO)含量以及对各胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GSH—PX)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)等酶活性的影响。结果表明,SFPS可显著降低L_(615)小鼠全血及肝脾LPO的含量,增加CAT、SOD的酶活性,提示SFPS具有清除L_(615)小鼠体内自由基,抗脂质过氧化作用。本文结果提示,SFPS的这些作用可能是其抗白血病作用的机理之一。     

荠苧黄酮对低压低氧小鼠心肌组织损伤的改善作用与机制研究

目的:研究荠苧黄酮对低压低氧小鼠心肌组织损伤的改善作用与机制.方法:将60只小鼠随机分为正常对照组、缺氧模型组、芦丁组和荠苧黄酮组,连续灌胃(ig)给药5 d,最后1次给药后,在模拟海拔8 000 m 环境停留12h,测定血清中肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactic dehydrog...     

三硝基甲苯亚慢性染毒大鼠某些生化指标的改变

【目的】　观察三硝基甲苯 (TNT)亚慢性染毒后 ,大鼠某些生化指标的改变。【方法】　大鼠亚慢性染毒后处死 ,留取肝脏和血清 ,测定有关的生化指标。【结果】　肝脏过氧化氢酶 (CAT)和超氧化物歧化酶 (SOD)活性明显高于对照组 ,而谷胱甘肽过氧化物酶 (GSH -Px)无明显改变。同时 ,血清中脂质过氧化 (LPO)水平显著高于对照组 ,铜蓝蛋白活性显著低于对照组。这种变化与已知的过氧化物小体增生剂安妥明引起的改变相类似。【结论】　推测TNT可能为过氧化物小体增生剂。     

Effects of verbascoside and luteolin on oxidative damage in brain of heroin treated mice

Extensive but fragmentary studies have shown: (i) heroin, morphine and opiates are able to induce reactive oxygen species (ROS) formation in several cells, (ii) they decrease the antioxidant defense system including enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and antioxidants, glutathione (GSH), Se, and vitamins. This study is to investigate the oxidative damage to DNA, proteins, and lipids in brain of mice administered heroin via intraperitoneal injection, and the effects of verbascoside and luteolin on this damage. All the indices of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl group and malondialdehyde (MDA) contents increased significantly compared to those of controls in the brains of heroin-administered mice, while the indices related to the in vivo antioxidative capacity, such as the ratio of GSH and oxidized glutathione (GSSG), and activities of SOD, CAT and GPx in the brain, and total antioxidant capacity (TAC) in serum significantly decreased. When heroin-dependent mice were treated with verbascoside or luteolin, oxidative stress status was limited.     

Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin -induced diabetic rats

Aim and Objectives:

In the present study, we have evaluated the antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of Phyllanthus amarus (PAAEt) in streptozotocin (STZ)-induced diabetic rats.

Materials and Methods:

PAAEt was administered at 200 mg/kg body weight/day to normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by gavage for eight weeks. During the experimental period, blood was collected from fasted rats at 10 days intervals and plasma glucose level was estimated. The plasma lipid profile was estimated at the end of experimental period. After the treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were also assayed.

Results:

The significant decrease in the body weight, hyperglycemia and hyperlipidemia observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt treatment in diabetic treated group (DT-group). D-group rats showed increased renal oxidative stress with increased LPO and protein oxidation. DT-group showed a significant decrease in renal LPO, protein oxidation and a significant increase in GSH content and GR, GPx and GST activities when compared with D-group. The activities of SOD and CAT decreased significantly in D-group, but were normalized in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant decrease in lipid profile, renal LPO and protein oxidation, with significant increase in renal GSH and activities of antioxidant enzymes compared to normal rats (N-group).

Conclusion:

Our results demonstrated that PAAEt with its antidiabetic, hypolipidemic and antioxidant properties could be a potential herbal medicine in treating diabetes and renal problems.     

Protective effect of Hygrophila spinosa against cisplatin induced nephrotoxicity in rats

Objective:

To evaluate the nephroprotective effect of methanolic extract of Hygrophila spinosa (HSME) (Acanthaceae) in (CP)-induced acute renal failure in rats.

Materials and Methods:

HSME (250 mg/kg and 500 mg/kg body weight), were administered orally to male wistar albino rats.CP was used to induce acute renal failure. The parameters studied included blood urea and serum creatinine and malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and GSH peroxidase activities. Histopathological examination was also carried out.

Results:

The results revealed that HSME pretreatment signiûcantly reduced blood urea and serum creatinine levels elevated by CP administration. Furthermore, HSME signiûcantly attenuated CP-induced increase in MDA and decrease in reduced GSH, and CAT and SOD and GSH peroxidase activities in renal cortical homogenates. Additionally, histopathological examination showed that HSME markedly ameliorated CP-induced renal tubular necrosis.

Conclusion:

The results indicate that the aerial parts of H. spinosa are endowed with nephroprotective activity.KEY WORDS: Cisplatin, Hygrophila spinosa, lipid peroxidation, nephrotoxicity     

Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats

A potential therapeutic approach to protect or reverse gentamicin-induced oxidative stress and nephrotoxicity would have more importance for clinical consequences. Therefore, the present study was designed to investigate the possible protective effects of lycopene against gentamicin-induced renal damage in rats. Male Sprague-Dawley rats were divided into four groups of six rats in each one; first group served as control. The other groups were treated intraperitoneally with gentamicin alone (100 mg kg(-1) per day) for six successive days, gentamicin for 6 days following 10 days of orally lycopene (4 mg kg(-1) per day) pre-treatment and 6-days of simultaneous lycopene and gentamicin. Biochemical and histopathological examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, urea, Na(+) and K(+) levels in plasma and malondialdehyde (MDA), reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney tissue. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and urea concentrations. The animals treated with gentamicin alone showed a significantly higher kidney MDA and lower GSH-Px and CAT activities but unaffected GSH concentrations when compared with the control group. Pre-treatment with lycopene produced amelioration in biochemical indices of nephrotoxicity in plasma. However, little changes were observed in the kidney MDA and GSH levels and GSH-Px and CAT activities when compared with the gentamicin treated group. The histological structures of the renal proximal tubules showed similar patterns. On the other hand, administration of simultaneous lycopene to rats produced amelioration in MDA and GSH levels and GSH-Px and CAT activities when compared with gentamicin group. In addition, simultaneous lycopene was found to reduce the degree of kidney tissue damage in histopathological findings. These results indicate that specially simultaneous treatment of lycopene might have produced amelioration in biochemical indices and oxidative stress parameters against gentamicin-induced nephrotoxicity, but pre-treatments with lycopene had no beneficial effects on these parameters. It was concluded that lycopene as a novel natural antioxidant might have protective effects against gentamicin-induced nephrotoxicity and oxidative stress in rats.     

D-青霉胺和二巯丙磺酸钠对汞致大鼠肾毒性的影响

目的　研究预投D- 青霉胺 (D- penicillamine ,DPA)和二巯丙磺酸钠 (2 ,3 - Dimercato 1 Propanesulfonate ,DMPS)对汞致急性肾毒性的保护作用及其机制。方法　 48只Wistar大鼠随机分成 6组。第 1组以 5mL/kg体重皮下注射质量分数为 0 . 9%的氯化钠溶液 ,第 2、3和 4组分别皮下注射 0 .75、1.5和 2 .5mg kgHgCl2 溶液。第 5、6组大鼠分别腹腔注射2 0 0 μmoLDMPS和 2 0 0 μmoLDPA ,2h后再投与 2 5mg/kgHgCl2 溶液。染毒 12h后 ,收集 12h尿样 ,测定尿N- 乙酰 - β- D- 氨基葡萄糖苷酶 (NAG)和尿碱性磷酸酶 (ALP)活力、尿蛋白和尿汞含量。染毒 48h后 ,切取肾脏和肝脏 ,分别测定肾脏和肝脏中的丙二醛 (MDA)和谷胱甘肽 (GSH)含量、谷胱甘肽过氧化物酶 (GSH- Px)活力、肝脏汞和肾脏汞含量。结果　DMPS显著降低NAG和ALP活力和尿蛋白含量 ;DPA明显降低NAG活力和尿蛋白含量 ,对ALP没有影响。DMPS显著降低肾脏MDA含量 ,而DPA对肾脏MDA含量没有影响。DMPS-和DPA两干预组在肾脏中GSH含量和GSH -Px活力都明显高于 2 . 5mg kg染汞组 ,差异有显著性。DPA能显著降低肾脏汞含量。结论　DMPS比DPA更能有效地保护肾功能。DMPS会显著减轻汞在肾脏的氧化损伤 ,而DPA则没有影响。DMPS和DPA能明显减少肾脏GSH和GSH- Px的耗     

Effect of bisphenol A on blood glucose,lipid profile and oxidative stress indices in adult male mice

Abstract

Bisphenol A (BPA), an endocrine-disrupting chemical, has been considered as a possible risk factor for diabetes and its complications. However, the underlying mechanisms of BPA-induced diabetes are not clear. The present study was performed to evaluate the effects of BPA on the hyperglycemia, lipid abnormalities and oxidative stress. In this study, the mice were divided into three groups of six animals each: One group as a control (C) and two other groups which exposed to 0.5 and 2?mg/kg concentrations of BPA. BPA powder was dissolved in sterile extra virgin olive oil and injected intraperitoneally to the tested groups, while the control group only received pure olive oil for 4 weeks. After 4 weeks, the changes of glucose, lipid profile reduced, total protein, glutathione (GSH), malondialdehyde (MDA), total antioxidant status (TAS), catalase (CAT) and super oxide dismutase (SOD) were determined in serum and pancreas. The results indicated that BPA dose-dependently increased the levels of blood glucose, lipid profile and MDA in the tested groups compared with the control group (p?<?0.001). BPA reduced significantly the levels of HDL-C and GSH in dose-dependent manner (p?<?0.001). BPA injection increased the levels of MDA and decreased the levels of GSH and TAS, and also the activities of SOD and CAT in the pancreas of exposed mice compared with the control group (p?<?0.05). In addition, body weight increased in the mice exposed to BPA compare to control animals. These results suggest that BPA exposure might induce hyperglycemia and its complications in adult male mice by induction of oxidative stress.