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[Mathematical modeling of calcium homeostasis in smooth muscle cells while activity of plasma membrane calcium pump is modulated]. [调节质膜钙泵活性时平滑肌细胞钙稳态的数学模型]。
Pub Date : 2013-09-01 DOI: 10.15407/ubj85.05.177
S. Karakhim, V. Gorchev, P. F. Zhuk, S. A. Kosterin
A mathematical model of intracellular calcium homeostasis in smooth muscle cells has been investigated by computer modelling method. The results of calculations showed that for the plasma membrane calcium pump (PMCA) the limiting rate (V(mPM)) increasing or the Michaelis constant (K(mPM)) decreasing result in a lowering of the Ca2+ concentration in cytosol and sarcoplasmic reticulum (SR); the slight V(mPM) decreasing or K(mPM) increasing result in fluent cytosolic Ca2+ strengthening due to slow basal influx (SBI) since a massive release of Ca2+ from SR does not occur. The further V(mPM) decreasing or K(mPM) increasing stimulate the Ca(2+)-induced Ca2+ release from SR and the system passes into oscillation mode; when the certain low V(mPM) or high K(mPM) level is reached the oscillations of Ca2+ concentration in cytosol are stopped, there is only first oscillation after which a new level of cytosolic Ca2+ concentration is formed fluently: this level is higher than in the initial basal condition (IBC). Sensitivity of myocytes with the lowering of V(mPM) or increasing K(mPM) to agonist action is rising but sensitivity of myocytes with increasing V(mPM) or decreasing K(mPM) to agonist action is reducing. If the PMCA parameters (V(mPM) or K(mPM)) are changed then passive influx of Ca2+ in cytosol from extracellular space remains virtually invariable and it is equal to SBI value during the whole process. Initial rate of PMCA in a new equilibrium condition (NEC) is equal virtually to initial rate in IBC: it allows to calculate a new value V(mPM) or K(mPM) from cytosolic Ca2+ concentration in NEC.
本文用计算机模拟方法研究了平滑肌细胞内钙稳态的数学模型。计算结果表明,对于质膜钙泵(PMCA),极限速率(V(mPM))的增加或Michaelis常数(K(mPM))的降低会导致胞浆和肌浆网(SR)中Ca2+浓度的降低;轻微的V(mPM)降低或K(mPM)增加导致细胞质内Ca2+增强,这是由于缓慢的基底内流(SBI),因为没有发生从SR大量释放Ca2+。V(mPM)的进一步降低或K(mPM)的进一步增加刺激Ca(2+)诱导的Ca2+从SR释放,系统进入振荡模式;当达到一定的低V(mPM)或高K(mPM)水平时,细胞质中Ca2+浓度的振荡停止,只有第一次振荡之后,细胞质中Ca2+浓度的新水平流畅地形成,该水平高于初始基础条件(IBC)。当V(mPM)降低或K(mPM)升高时,肌细胞对激动剂的敏感性升高,而V(mPM)升高或K(mPM)降低时,肌细胞对激动剂的敏感性降低。如果PMCA参数(V(mPM)或K(mPM))发生变化,则细胞质中Ca2+从细胞外空间的被动内流几乎保持不变,并且在整个过程中等于SBI值。PMCA在一个新的平衡条件下的初始速率(NEC)几乎等于IBC的初始速率:它允许计算一个新的值V(mPM)或K(mPM)从细胞质Ca2+浓度在NEC。
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引用次数: 1
[Influence of oxidative stress on the level of genes expression Tgfb1 and Hgf in rat liver upon long-term gastric hypochlorhydria and administration of multiprobiotic Symbiter]. [氧化应激对长期胃低氯酸和多益生菌Symbiter给药大鼠肝脏Tgfb1和Hgf基因表达水平的影响]。
Pub Date : 2013-09-01 DOI: 10.15407/UBJ85.05.114
K. Dvorshchenko, O. Bernyk, A. S. Dranytsyna, S. Senin, L. Ostapchenko
Free-radical processes upon long-term omeprazole-induced gastric hypochlorhydria in the rat liver were researched. Intensification of oxidative processes in the liver tissue upon gastric hypoacid state was established: overproduction of superoxide anion, hydrogen peroxide, the quantitative changes of lipid functional groups, increased level of lipid peroxidation products, and augmentation of xanthine oxidase activity. The expression of Tgfb1 gene increased, while the expression of Hgf gene was not detected upon long-term suppression of gastric acid secretion of hydrochloric acid by omeprazole that indicated possible development of liver fibrosis. Abovementioned parameters were only partially restored to control values in the case of simultaneous administration of multiprobiotic "Symbiter acidophilic" concentrated with omeprazole, thus indicating the ability of this preparation to counteract the development of oxidative damages in liver tissues upon long-term gastric hypoacidic conditions.
研究了奥美拉唑引起的大鼠胃次氯酸对肝脏自由基的影响。胃酸状态下肝组织氧化过程增强:超氧阴离子、过氧化氢过量产生,脂质官能团数量改变,脂质过氧化产物水平升高,黄嘌呤氧化酶活性增强。在奥美拉唑长期抑制盐酸胃酸分泌后,Tgfb1基因表达增加,Hgf基因未见表达,提示可能发生肝纤维化。在同时给予与奥美拉唑浓缩的“嗜酸共生菌”复合益生菌时,上述参数仅部分恢复到控制值,这表明该制剂能够抵消胃长期低酸性条件下肝组织氧化损伤的发展。
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引用次数: 12
[Antitoxic and antioxidant effects of N-stearoylethanolamin in the content of nanocomposite complex with doxorubicin in organs of mice with Lewis carcinoma]. [n -硬脂酰乙醇胺与阿霉素纳米复合物含量对Lewis癌小鼠器官的抗毒和抗氧化作用]。
Pub Date : 2013-09-01 DOI: 10.15407/ubj85.05.097
Ie. A. Hudz, N. Hula, T. Horid’ko, Iu M Bashta, A. I. Voieĭkov, A. Berdyshev, H. Kosiakova, R. R. Panchuk, R. Stoika, A. Riabtseva, O. Zaichenko
The aim of the study was to evaluate the possibility to reduce the doxorubicin toxic effects by its immobilization with N-stearoylethanolamine (NSE) on nanocarier polyethylene glycol. The studied parameters of the doxorubicin toxicity were: the level of creatinine in the mice blood plasma and activity of alanine aminotransferase and aspartate aminotransferase in the blood plasma of mice. The activity of catalase superoxide dismutase, glutathione peroxidase and intensity of lipid peroxidation was determined in the tissues of the heart, kidneys and liver. Doxorubicin in the content of nanocarrier alone caused an increase of serum creatinine and aspartateaminotrasferase activity in plasma of experimental animals with carcinoma. Nanocomposite which contained doxorubicin and NSE, did not cause an increase of these parameters. It has been shown that the administration of a carrier containing doxorubicin to mice with Lewis lung carcinoma caused the decrease of catalase activity in mice with carcinoma. The combination of NSE and doxorubicin on the carrier led to the normalization of this parameter to the level of intact animals. NSE immobilized on a carrier together with doxorubicin caused a decrease in the activity of superoxide dismutase in the kidney tissue of mice with tumor. The tumor growth caused the increase of the of superoxide dismutase in mice. The administration of a carrier which contained doxorubicin and NSE normalized superoxide dismutase in heart tissue contrary of kidney. The obtained results show the antitoxic and antioxidant effects of N-stearoylethanolamine immobilized in the nanocarrier complex together with doxorubicin.
本研究的目的是评估n -硬脂酰乙醇胺(NSE)在纳米载体聚乙二醇上固定阿霉素毒性作用的可能性。阿霉素毒性的研究参数为:小鼠血浆肌酐水平和小鼠血浆丙氨酸转氨酶和天冬氨酸转氨酶活性。测定心、肾、肝组织过氧化氢酶超氧化物歧化酶、谷胱甘肽过氧化物酶活性及脂质过氧化强度。纳米载体中单独添加阿霉素可引起实验动物血清肌酐和血浆天冬氨酸氨基转移酶活性升高。含有阿霉素和NSE的纳米复合材料没有引起这些参数的增加。研究表明,给Lewis肺癌小鼠服用含有阿霉素的载体可导致肺癌小鼠过氧化氢酶活性降低。NSE联合载体上的阿霉素使该参数归一化到完整动物的水平。NSE与多柔比星一起固定在载体上,引起肿瘤小鼠肾组织超氧化物歧化酶活性降低。肿瘤生长引起小鼠体内超氧化物歧化酶升高。含有阿霉素和NSE的载体的管理使心脏组织的超氧化物歧化酶与肾脏相反。结果表明,n -硬脂酰乙醇胺与阿霉素固定在纳米载体配合物中具有抗氧化和抗毒作用。
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引用次数: 1
[Use of vitamins for correction of the functional state of cytochrome P450 systems in experimental allergic encephalomyelitis]. [使用维生素纠正实验性变应性脑脊髓炎细胞色素P450系统的功能状态]。
Pub Date : 2013-09-01 DOI: 10.15407/ubj85.05.137
E. Pasichna, H. V. Donchenko, A. Burlaka, V. S. Nedzvets'kyĭ, I. Sydoryk, I. I. Hanusevych, N. V. Delemenchuk
It is known that inflammatory cytokines, which level is significantly increased in the pathogenesis of multiple sclerosis (MS), as well as interferon-beta, which is used to treat autoimmune diseases, can inhibit cytochrome P450-dependent processes of detoxification and biotransformation. The uncontrolled decrease of the activity of these processes may have a negative affect on the state of patients, so it is urgent to study the functional state of the cytochrome P450 system and to develop effective means for its regulation in these conditions. The effect of vitamin D3 and efficiency of its composition with vitamins B1, B2, B6, PP, E, alpha-lipoic, alpha-linolenoic acid and mineral substances (Mg, Zn, Se) in prevention of a functional state changes of cytochrome P450- and b5-dependent systems of the rat brain and liver endoplasmic reticulum at EAE are investigated. It has been shown that the essential decrease of the level of these cytochromes is observed both in the brain and liver. In addition the level of activity of NADH- and NADPH-oxidoreductases, which are part of microsomal electron transport chain components and coupled with monooxigenases, was reduced. These changes confirm the disturbances of a redox state and functional activity of detoxication and biotransformation systems in the studied animal tissues. Supplement of vitamin D3 as well as the composition of biologically active substances, which we developed earlier, effectively eliminated the decrease of the level of cytochromes and activities of NADH-oxidoreductase in immunised rat tissues. Normalization of these disturbances can be explained by antioxidant and membrane-stabilizing properties of applied substances, and also by the ability to reduce the activity of inflammatory reactions by regulation of the level of inflammatory cytokines in rat organism at EAE. Thus the studied vitamin-mineral composition appeared to be more effective to normalize the found disturbances and it can be useful for prevention of exacerbations and for improvement of a status of patients with multiple sclerosis and other diseases, which are accompanied with hyperactivation of immune system.
众所周知,在多发性硬化症(MS)发病过程中水平显著升高的炎性细胞因子,以及用于治疗自身免疫性疾病的干扰素- β,可以抑制细胞色素p450依赖的解毒和生物转化过程。这些过程活性的不受控制的下降可能会对患者的状态产生负面影响,因此迫切需要研究细胞色素P450系统在这些情况下的功能状态,并开发有效的调控手段。研究了维生素D3及其与维生素B1、B2、B6、PP、E、α -硫辛酸、α -亚油酸和矿物质(Mg、Zn、Se)的组合对EAE时大鼠脑和肝内质网细胞色素P450-和b5依赖系统功能状态变化的影响。研究表明,在大脑和肝脏中都观察到这些细胞色素水平的基本下降。此外,与单氧化酶偶联的微粒体电子传递链组分NADH-和nadph -氧化还原酶活性水平降低。这些变化证实了所研究动物组织中氧化还原状态和解毒和生物转化系统功能活性的干扰。补充维生素D3和我们早期开发的生物活性物质的组成,有效地消除了免疫大鼠组织中细胞色素水平和nadh氧化还原酶活性的下降。这些干扰的正常化可以通过所应用物质的抗氧化和膜稳定特性来解释,也可以通过调节EAE大鼠机体中炎症细胞因子的水平来降低炎症反应的活性。因此,所研究的维生素矿物质成分似乎更有效地使发现的紊乱正常化,它可以用于预防恶化和改善多发性硬化症和其他疾病患者的状态,这些疾病伴随着免疫系统的过度激活。
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引用次数: 0
[Distribution of 5-fluorouracil between lymphocytes and blood plasma]. 5-氟尿嘧啶在淋巴细胞和血浆中的分布。
Pub Date : 2013-07-01 DOI: 10.15407/ubj85.04.094
M. A. Stashkevich, E. Khomutov, O. Shatova, Iu V Dumanskiĭ, I. Zinkovich
In blood plasma of 8 healthy volunteers with resuspended lymphocytes incubated with 5-fluorouracil (5-FU) the drug distribution between cells and liquid was assessed by means of HPLC. Rapid accumulation of 5-FU in lymphocytes was proved (the drug concentration on the 3-rd minute is 2.5-fold higher than in plasma) as well as the absence of temporal changes of 5-FU content both in lymphocytes and blood plasma during 30 minutes of experiment.
采用高效液相色谱法测定8例健康志愿者外周血淋巴细胞重悬与5-氟尿嘧啶(5-FU)孵育后血浆中药物在细胞和液中的分布。实验证明5-FU在淋巴细胞中快速积累(第3分钟的药物浓度比血浆中高2.5倍),实验30分钟淋巴细胞和血浆中5-FU含量均无时间变化。
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引用次数: 1
[Kinetic properties of calixarene C-90 action on the myometrial plasma membrane Ca2+,Mg2+-Atpase activity and on the Ca2+ concentration in unexcited cells of the myometrium]. [杯芳烃C-90对肌层质膜Ca2+、Mg2+- atp酶活性和肌层非兴奋细胞Ca2+浓度的动力学性质]。
Pub Date : 2013-07-01 DOI: 10.15407/ubj85.04.020
Veklich To, Shkrabak Oa, Mazur IuIu, Rodik Rv, Boĭko Vi, V. Kalchenko, S. Kosterin
Plasma membrane Ca2+,Mg2+-ATPase is an important element of general myometrium tonus control mechanism, which also makes a contribution to muscle tension relaxation after its contraction. Expiriments were done on the myometrial cell plasma membrane suspension, which was treated with 0.1% digitonin solution. The authors have investigated the inhibitory action of calix[4]arene C-90 (5,11,17,23-tetra(trifluor) methyl(phenylsulphonylimino)-methylamino-25,26,27,28-tetra propoxi-calix[4]arene) on the Ca2+,Mg2+-ATPase activity (the magnitude of 10.5 was 20.2 +/- 0.5 mkM). The inhibitory action of calix[4]arene C-90 on the activity of Ca2+, Mg2+-ATPase is explained as cooperative action of four trifluormethyl(phenylsulfonylimino)methylamino groups that are spatially oriented on the calix[4]-arene base rather than with the action of tetra-phenol macrocycle or separate pharmacophore sulphonilamidin groups. Considering established kinetic pattern of calix[4]arene C-90 inhibitory action on the plasma membrane Ca2+,Mg2+-ATPase activity, stationary kinetical model of basal calcium concentration control in unexcited uterus myocytes was developed. It is assumed that obtained results may be promising for creation of new generation ("supramolecular") pharmacological agent - uterus basal tonus stimulator - on the base of calix[4] arene C-90.
质膜Ca2+,Mg2+- atp酶是一般肌张力控制机制的重要组成部分,它也有助于肌肉收缩后的紧张松弛。实验采用0.1%洋地黄苷溶液处理子宫肌层细胞膜悬浮液。作者研究了杯[4]芳烃C-90(5,11,17,23-四(三氟)甲基(苯基磺酰亚胺)-甲基氨基-25,26,27,28-四丙氧杯[4]芳烃)对Ca2+,Mg2+- atp酶活性的抑制作用(10.5量级为20.2 +/- 0.5 mkM)。杯[4]芳烃C-90对Ca2+, Mg2+- atp酶活性的抑制作用可以解释为杯[4]芳烃碱基上四个三氟甲基(苯基磺酰基)甲基胺基的协同作用,而不是与四酚大环或单独的药效团磺胺基的协同作用。考虑到杯[4]芳烃C-90抑制质膜Ca2+,Mg2+- atp酶活性的既定动力学模式,建立了非兴奋子宫肌细胞基础钙浓度控制的稳态动力学模型。假设所获得的结果可能有希望在杯[4]芳烃C-90的基础上创造新一代(“超分子”)药理学药物-子宫基底张力刺激剂。
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引用次数: 1
[Influence of Ca2+ on kinetic parameters of pancreatic acinar mitochondria in situ respiration]. [Ca2+对胰腺腺泡线粒体原位呼吸动力学参数的影响]。
Pub Date : 2013-07-01 DOI: 10.15407/ubj85.04.048
B. O. Man'ko, V. V. Man'ko
The dependence of respiration rate of rat permeabilized acinar pancreacytes on oxidative substrates concentration was studied at various [Ca2+] - 10-8-10-6 M. Pancreacytes were permeabilized with 50 microg of digitonin per 1 million cells. Respiration rate was measured polarographically using the Clark electrode at oxidation of succinate or pyruvate either glutamate in the presence of malate. Parameters of Michaelis-Menten equation were calculated by the method of Cornish-Bowden or using Idi-Hofsti coordinates and parameters of Hill equation - using coordinates {v; v/[S]h}. In the studied range of [Ca2+] the kinetic dependence of respiration at pyruvate oxidation is described by the Michaelis-Menten equation, and at oxidation of succinate or glutamate - by Hill equation with h = 1.11-1.43 and 0.50-0.85, respectively. The apparent constant of respiration half-activation (K0.5) did not significantly change in the studied range of [Ca2+] while at 10-7 M Ca2+ it was 0.90 +/- 0.06 mM for succinate, 0.096 +/- 0.007 mM for pyruvate and 0.34 +/- 0.03 mM for glutamate. Maximum respiration rate Vax at pyruvate oxidation increased from 0.077 +/- 0.002 to 0.119 +/- 0.002 and 0.140 +/- 0.002 nmol O2/(s.million cells) due to the increase of [Ca2+] from 10-7 to 5x10-7 or 10-6 M, respectively. At oxidation of succinate or glutamate Ca2+ did not significantly affect Vmax Thus, the increase of [Ca2+] stimulates respiration of mitochondria in situ of acinar pancreacytes at oxidation of exogenous pyruvate (obviously due to pyruvate dehydrogenase activation), but not at succinate or glutamate oxidation.
研究了不同[Ca2+] - 10-8-10-6 m浓度下大鼠腺泡胰腺细胞透性呼吸速率对氧化底物浓度的依赖性。在琥珀酸盐或丙酮酸盐或谷氨酸盐存在的情况下,使用克拉克电极用极谱法测量呼吸速率。Michaelis-Menten方程的参数采用Cornish-Bowden法或采用Idi-Hofsti坐标计算,Hill方程的参数采用坐标{v;v / h [S]}。在研究的[Ca2+]范围内,丙酮酸氧化时呼吸的动力学依赖由Michaelis-Menten方程描述,琥珀酸或谷氨酸-氧化时呼吸的动力学依赖由Hill方程描述,h分别为1.11-1.43和0.50-0.85。在10-7 M Ca2+条件下,琥珀酸盐的表观呼吸半激活常数(K0.5)为0.90 +/- 0.06 mM,丙酮酸盐为0.096 +/- 0.007 mM,谷氨酸盐为0.34 +/- 0.03 mM。由于[Ca2+]浓度从10-7增加到5 × 10-7或10-6 M,丙酮酸氧化时的最大呼吸速率Vax分别从0.077 +/- 0.002增加到0.119 +/- 0.002和0.140 +/- 0.002 nmol O2/(s百万细胞)。因此,在外源性丙酮酸氧化(显然是由于丙酮酸脱氢酶激活)时,[Ca2+]的增加刺激了腺泡胰腺细胞线粒体的原位呼吸,而在琥珀酸或谷氨酸氧化时则没有。
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引用次数: 4
[Reactive oxygen forms and Ca ions as possible intermediaries under the induction of heat resistance of plant cells by jasmonic acid]. [茉莉酸诱导植物细胞耐热性的活性氧形式和钙离子作为可能的中介]。
Pub Date : 2013-06-27 DOI: 10.15407/UBJ85.03.062
I. V. Karpets, Iu E Kolupaev, T. O. Iastreb, A. I. Oboznyi, N. V. Shvidenko, A. A. Lugovaia, A. Vainer
The participation of reactive oxygen species (ROS) and calcium ions in realization of influence of exogenous jasmonic acid (JA) on the heat resistance of wheat coleoptiles has been investigated. Influence of 1 microM JA caused the transitional intensifying of generation of superoxide anion-radical (O2*-) and hydrogen peroxide in coleoptiles with the maximum within 15-30 minutes after the treatment beginning. Within the first hour after the beginning of coleoptiles treatment with JA the increase of superoxide dismutase (SOD) activity was noted. Later on (within 5-24 hours after the treatment beginning) there was the lowering of ROS generation by coleoptiles of experimental variant, and the SOD activity approached the control value. Intensifying of generation of superoxide radical induced by JA was suppressed by the antioxidant ionol and was partially levelled by imidazole (inhibitor of NADPH-oxidase), EGTA (chelator of extracellular calcium) and lanthanum chloride (calcium channels blocker). Pretreatment of coleoptiles with the ionol, imidazole, EGTA and LaC3l3 also partially removed the effect of increase of their resistance to the damaging heating caused by exogenous JA. It is supposed that the ROS generated with participation NADPH-oxidase, which activity depends on the receipt of calcium ions from extracellular space in the cytosol, are involved in realization of physiological effects of JA.
研究了活性氧(ROS)和钙离子参与实现外源茉莉酸(JA)对小麦胚囊耐热性的影响。1 μ m茉莉酸的影响使胚囊中超氧阴离子自由基(O2*-)和过氧化氢的生成过渡性增强,并在处理开始后15-30分钟内达到最大值。在JA处理胚芽后1小时内,超氧化物歧化酶(SOD)活性明显升高。随后(处理开始后5-24小时内),实验变异体胚囊ROS生成降低,SOD活性接近控制值。抗氧化离子醇可抑制JA诱导的超氧自由基生成,而咪唑(nadph氧化酶抑制剂)、EGTA(细胞外钙螯合剂)和氯化镧(钙通道阻滞剂)可部分抑制JA诱导的超氧自由基生成。用离子醇、咪唑、EGTA和LaC3l3对胚芽包进行预处理,也部分地消除了外源JA对胚芽包抗热损伤的影响。据推测,在nadph氧化酶参与下产生的ROS参与了JA生理作用的实现,其活性依赖于细胞质中从胞外空间接收钙离子。
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引用次数: 4
[Adjuvant properties of polymer based on acrylic acid]. [丙烯酸基聚合物的助剂性能]。
Pub Date : 2013-05-01 DOI: 10.15407/ubj85.03.069
M. Kozak, A. Oliinyk, O. Zaichenko, V. Vlizlo
Adjuvant properties of the polymer containing acrylic acid, glycidyl methacrylate, triethylene glycol methacrylate and butyl acrylate have been established. Antibodies to ovalbumin and bovine serum albumin in the blood of mice were revealed using dot blot analysis and immunoenzyme analysis when applying the investigated polymer as a carrier of these protein antigens. Adjuvant properties of the polymer were compared to aluminum hydroxide, which is a component of many traditional vaccines. Experimental polymer was a stronger adjuvant because it led to an increase of specific antibodies against ovalbumin and bovine serum albumin.
确定了丙烯酸、甲基丙烯酸缩水甘油酯、甲基丙烯酸三甘醇和丙烯酸丁酯组成的聚合物的助剂性能。将所研究的聚合物作为卵清蛋白和牛血清白蛋白抗原的载体,采用点印迹分析和免疫酶分析发现小鼠血液中存在卵清蛋白和牛血清白蛋白的抗体。将该聚合物的佐剂性能与氢氧化铝进行了比较,氢氧化铝是许多传统疫苗的组成部分。实验聚合物是一种较强的佐剂,因为它导致针对卵清蛋白和牛血清白蛋白的特异性抗体增加。
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引用次数: 4
[Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine]. [二氢吡咯和马来酰亚胺衍生物对正常大鼠和二甲肼致结直肠癌大鼠肝脏和结肠状态的影响]。
Pub Date : 2013-05-01 DOI: 10.15407/ubj85.03.074
H. Kuznietsova, O. Lynchak, M. O. Danylov, I. Kotliar, V. K. Rybal'chenko
No liver and colon alterations in rats, caused by cytostatic compounds 5-amino-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one (D1) and 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) when administered over a long time were found, as evidenced by the histopathological data and the data of activity of transaminases, alkaline phosphatase and lactate dehydrogenase in the blood serum. D1 and MI-1 in vivo decrease the total area of DMH-induced colon tumors in rats by 46-60%. Furthermore, D1 and MI-1 partially protect the liver and colon mucosa from toxic effects caused by 1,2-dimethylhydrazine (DMH) reducing DNA oxidative modifications, as evidenced by urine 8-hydroxydeoxyguanosine level. The effects of both compounds are similar, but MI-1 is less toxic for the liver and colon of intact animals possessing more pronounced antitumor activity and protective properties in the setting of chemically induced carcinogenesis.
组织病理学数据和血清转氨酶、碱性磷酸酶、乳酸脱氢酶活性数据均证实,长期给药细胞抑制剂5-氨基-4-(1,3-苯并噻唑-2-基)-1-(3-甲氧基苯基)-1,2-二氢- 3h -吡咯-3-酮(D1)和1-(4- cl -苄基)-3- cl -4-(cf3 -苯胺)- 1h -吡咯-2,5-二酮(MI-1)对大鼠肝脏和结肠无明显影响。体内D1和MI-1可使dmh诱导的大鼠结肠肿瘤总面积减少46-60%。此外,D1和MI-1部分保护肝脏和结肠黏膜免受1,2-二甲基肼(DMH)减少DNA氧化修饰引起的毒性作用,这一点可以通过尿8-羟基脱氧鸟苷水平得到证实。这两种化合物的作用是相似的,但MI-1对完整动物的肝脏和结肠的毒性较小,在化学诱导致癌的环境中具有更明显的抗肿瘤活性和保护特性。
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引用次数: 19
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Ukrains'kyi biokhimichnyi zhurnal
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