Colchicine-induced inhibition of fat globule development in hepatocytes of rats injected with ethionine

To examine the effect of colchicine on ethionine-induced fatty liver, adult female rats were starved overnight and then injected i.p. with 1 g/kg ethionine at 11th hour of fasting; then a half of the rats were also injected i.p. with 2.5 mg/kg colchicine twice at 3 and 6 h after the single administration of ethionine. Similarly, fasted control rats were injected i.p. with vehicle alone at the above times. All of the rats were sacrificed after a 20-h fast, and the hepatocytes in periportal areas were observed ultrastructurally. In addition, total lipids in the liver tissue were extracted and determined biochemically. Although similar significant increases of triglyceride were observed in the liver tissue of all ethionine-injected rats, the hepatocytes in the group treated with both chemicals had fewer cytoplasmic fat globules (CFG) than those in the group treated with ethionine only. On the other hand, the diameters of markedly increased membrane-bound lipid particles (MLP) in the double-treated group were distributed mainly in the range 0.2-0.4 micron, compared with those (0.1-0.2 micron) in the other groups. These findings indicate that colchicine inhibits the development of CFG in ethionine-injured hepatocytes.     

The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats

This study aims to determine the effects of grape seed and colchicine on carbon tetrachloride (CCl₄) induced hepatic damage and on some serum biochemical parameters. Sixty male Wistar albino rats (200–250 g) were randomly divided into six groups (ten rats/group) and included the control group the group were given isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group treated i.p. injection of CCl₄ (1.0 mL/kg b.w) in corn oil twice in the first week, Groups 3 and 4 injected with CCl₄ as described for group 2 and the rats were orally given (100 mg/kg b.w) GSE and i.p. injected (10 μg/rat) with colchicine for four weeks, respectively and groups 5 and 6 were the grape seed and colchicine control groups in which rats were orally given grape seed (100 mg/kg b.w) and i.p. injected with colchicine (10 μg/rat), respectively. Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration, changes ranging from degenerative to necrotic, increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2, treated with CCl₄. Histological hepatic changes in the rats in group 3 and 4 were similar to those in group 2. The levels of serum total protein, albumin and globulin decreased in groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT) activities increased. The lowest alkaline phosphatase (ALP) activities were in groups 4 and 5. We concluded that GSE and colchicine have not sufficient ameliorative effects to CCl₄ induced acute hepatic damage.     

Hepatoprotection by malotilate against carbon tetrachloride-alcohol-induced liver fibrosis

Subchronic treatment of male rats with carbon tetrachloride (CCl₄, twice weekly 0.2 ml/kg p.o) and feeding a 5% alcohol solution instead of drinking water led to a nearly complete liver cirrhosis in all animals within 4 weeks. This was also documented by a three fold increase in hepatic total hydroxyproline content. Steatosis was quantified by enhanced liver triglyceride concentrations and acute necroses by increments of serum enzyme activities (GPT, SDH). Daily oral treatment with malotilate (100 mg/kg) totally prevented the development of liver cirrhosis, hepatic hydroxyproline accumulation and increases in serum enzyme activities induced by CCl₄-alcohol. In cianidanol-treated rats (100 mg/kg p.o.) only portoseptal fibrosis was seen, however hydroxyproline and triglyceride accumulation as well as enhanced serum enzyme activities were not suppressed. D-penicillamine (300 mg/kg p.o.) and colchicine (50 g/kg i.p.) failed to protect rats against CCl₄-alcohol induced fibrosis, necrosis and steatosis in this model.     

Evidence for a role of bradykinin in experimental pain models

Pretreatment with captopril, a kininase II inhibitor, at 10 mg/kg i.p. or s.c., significantly increased the writhing response induced by a minimum effective dose (0.75 mg/kg i.p.) of phenylbenzoquinone (PBQ), by 91–148%. 1,10-Phenanthroline, a carboxypeptidase B inhibitor (2 mg/kg i.p.), in combination with captopril enhanced the algesic effect of PBQ by 309–360%. Captopril also doubled the number of writhes induced by a minimum effective dose of BK (5 g/kg i.p.) in PGE₂-pretreated mice. The writhing responses induced by higher doses of PBQ or BK were not affected by these inhibitors. The hyperalgesic effect of BK (1 g) injected into the hindpaw of rats was significantly increased and prolonged by coinjection of captopril (30 g) and 1,10-phenanthroline (30 g) and was prevented by carboxypeptidase B (1 mg). These data indicate that BK plays a role in pain in these models, a role which appears of greatest relevance at threshold algesic stimulation.     

德都红花-7味散对CCl4诱导实验性肝纤维化疗效和IL-1、IL-6、TNF-α的影响

目的:观察德都红花-7味散对CCl4所致实验性肝纤维化疗效和对IL-1、IL-6、TNF-α的影响,探讨该药的作用机制。方法:将大鼠随机分为5组,除空白对照组,其余各组腹腔注射30%四氯化碳橄榄油溶液诱导大鼠形成肝纤维化;同时德都红花-7味散低、高剂量组和秋水仙碱阳性对照组分别灌胃德都红花-7味散每日0.62 g/kg、1.04 g/kg和秋水仙碱0.4 mg/kg;于第7周末,采集血清和肝组织,酶联免疫吸附试验检测纤维化指标HA、LN、PCⅢ、ⅣC和血清TNF-α、IL-1、IL-6含量,并用HE、Gomori、Masson染色观察肝组织病理学变化,采用2000年西安会议制定的《肝纤维化诊断及疗效评估共识》和《肝纤维化分期半定量评估系统Ishak》对肝纤维化程度进行分级、分期和评分。结果:与模型组比较德都红花-7味散低剂量组血清和肝组织HA、LN、PCⅢ、ⅣC、Hyp含量,炎症活动度及纤维化程度半定量值,血清TNF-α、IL-1、IL-6含量均明显降低,P<0.05;高剂量组血清HA、ⅣC,肝组织LN、ⅣC含量,炎症活动度及纤维化程度半定量值,血清TNF-α含量均明显降低,P<0.05;秋水仙碱组肝组织HA含量升高、ⅣC含量下降,有显著性差异,P<0.05;炎症活动度和纤维化程度半定量值无显著性差异,P>0.05;血清TNF-α、IL-1、IL-6含量升高,有显著性差异,P<0.05。与空白对照组比较德都红花-7味散低剂量组血清HA、PCⅢ、ⅣC,肝组织LN、PCⅢ、ⅣC,德都红花-7味散高剂量组血清PCⅢ、ⅣC,肝组织ⅣC含量无显著性差异,P>0.05。结论:德都红花-7味散能够明显改善CCl4所诱导实验性肝纤维化组织病理变化,降低肝纤维化指标HA、LN、PCⅢ、ⅣC和血清IL-1、IL-6、TNF-α含量,具有抗肝纤维化作用。     

Effects of jnk inhibitor on inflammation and fibrosis in the ovary tissue of a rat model of polycystic ovary syndrome

Objective: In our study, we aimed to investigate the effects of Jun N-terminal kinase inhibitor (SP600125) on fibrosis and inflammation in rats with polycystic ovary syndrome (PCOS). Method: 50 Wistar-albino rats were divided into five groups (n=10 each): control group, sham group, PCOS group, SP600125+ PCOS group and SP600125 group. In the estradiol valerate (EV)-treated group in which PCOS was injected with a single 4 mg/kg i.p. of EV in 0.2 ml sesame oil and the rats were sacrificed on day 60. The estradiol valerate (EV)-treated + SP600125-treated group was injected with a single 4 mg/kg i.p. of EV in 0.2 ml sesame oil. As of day 60, the treatment group was additionally given 15 mg/kg i.p. of SP600125 once daily for 4 consecutive days and the rats were sacrificed on day 65. Histopathological findings (ovarian morphology, edema, inflammatory cell infiltration, vascular congestion and hyperemia) and collagen type IV immunoexpression were assessed. Results: The SP600125+ PCOS group showed a significant level of improvement in ovarian follicle morphology, edema, inflammatory infiltrate, vascular congestion and hyperemia as compared with the PCOS group. Furthermore, collagen type IV immunoexpression showed a significant reduction in staining intensity on the theca cell layer and ovary stroma as compared to the PCOS group. Conclusion: This study demonstrates the therapeutic effect of SP600125 in the prevention of PCOS in an experimental model.     

Chemopreventive Efficacy of Ginger (Zingiber Officinale) in Ethionine Induced Rat Hepatocarcinogenesis

Ginger (Zingiber officinale Rosco) is widely used in foods as a spice all around the world. It has been reported to have antioxidant and anticarcinogenic properties. We investigated the effect of ginger in ethionine induced rat hepatocarcinogenesis. Male Wistar rats were divided into 5 groups: group 1 and 2 served as controls and they received normal rat chow and olive oil respectively. Group 3 was fed with ginger oleoresin dissolved in olive oil at 100 mg/kg body wt. Group 4 was fed with choline deficient diet and 0.1% ethionine in drinking water (CDE diet), and group 5 received ginger with CDE diet. Blood samples were taken from the orbital sinus at 0 and 8 weeks of experiment for the determination of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and lipid peroxidation end product, malondialdehyde (MDA). Rats were also killed at 8 weeks for the observation of liver tumor formation. CDE diet induced the formation of liver nodules in rats and increased SOD activity. However, it had no effect on catalase, GPx and MDA levels when compared to both controls at 8 weeks of experiment. When CDE rats were treated with ginger, the formation of liver tumour, SOD activity and MDA level reduced, catalase activity was increased but no change was observed for GPx activity when compared to CDE group. In conclusion, ginger supplementation suppressed liver carcinogenesis by scavenging the free radical formation, and by reducing lipid peroxidation.     

Cytokeratin filaments of the liver of BALB/c mice as a sensitive marker of liver damage. Computer-aided characterization with the image analysing system "IBAS".

The cytoskeleton forms a complex structural network which is of major importance for both structural integrity and physiologic functions of the cell. The aim of the present investigation was to investigate whether hepatotoxic effects of nitrosamine and colchicine can be detected through changes in the cytokeratin filament system which is an important component of the cytoskeleton. Groups of 10 male and 10 female newborn BALB/c mice were treated with either 25 micrograms dimethylnitrosamine (DMN) injected intraperitoneally on the day of birth; or with a daily subcutaneous injection of 0.12 micrograms/kg b.w. colchicine starting at ten weeks of age. A third group of mice served as untreated controls. All animals were held under standard laboratory conditions until necropsy at 16 weeks of age. The group injected with DMN received 0.05% phenobarbital with their drinking water after weaning. The histologic changes in the liver tissue were characterized by light microscopy. Changes of the cytokeratin filaments were visualized by the indirect immunofluorescent technique and quantified by using the image analysing system "IBAS". The cytokeratin filaments in the DMN group were markedly increased in amount and had a variety of morphological alterations. These effects could be measured quantitatively and did not indicate any sex-dependent behavior. The colchicine group did not display any structural changes in the cytokeratin filaments but sex-dependent changes in the amount of keratin material was revealed by image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunomodulating effect of inositol hexaphosphate against Aeromonas hydrophila-endotoxin

The present study was carried out to evaluate the effect of inositol hexaphosphate (IP6) administration on endotoxemia as an example of the systemic inflammatory response. Mice were divided into three groups as follows: First group, remained as a naive group injected intraperitoneally (i.p.) with PBS (pH 7.4; 0.2 ml/mice) at intervals parallel to the treated groups. The second group was injected i.p. with the lipopolysaccharide (LPS) of Aeromonas hydrophila once a week for four weeks at a dose of LPS suspension: 20 mg/kg mice/week. The third group was injected with the same LPS dose and synergistically intubated with IP6 three times a week for four weeks at a total dose of 4 0mg/kg. At different experimental periods (1, 2, 3 and 4 weeks), six animals from each group were sacrificed under mild diethyl ether anesthesia. Blood and sera were taken for the estimation of phagocytic activity, electrophoretic pattern of proteins and immunoglobulin levels. Also, a slice of liver was homogenized to estimate the respiratory burst enzymes activities and nitric acid synthesis. Histopathological changes of hepatic tissues were investigated. In the LPS-treated group, marked increase in the phagocytic activities and nitric oxide synthesis, and a decrease in hepatocyte catalase, total peroxidase and superoxide dismutase activities were observed. The histopathological features revealed a degeneration and highly mitotic division within the hepatic nuclei in addition to some karyomegaly and nuclear pyknosis. During the treatment period, liver sections of the LPS+IP6 group showed somewhat regenerative features. Reduction in the toxicity of free radicals by IP6 was observed and the IP6 effect seemed to be responsible for the observed ameliorative influence.     

银杏叶提取物对2型糖尿病大鼠肝脏糖皮质激素受体表达的影响

目的： 观察银杏叶提取物（EGB）对2型糖尿病大鼠肝脏糖皮质激素受体(GR)表达的影响,并探讨其机制。方法：雄性SD大鼠30只随机均分成3组：正常对照组、糖尿病对照组、EGB干预组。后两组采用高脂饮食4周,按30 mg/kg 腹腔注射链脲佐菌素（STZ） 诱导2 型糖尿病大鼠模型, EGB干预组给予50 mg·kg-1·d-1EGB连续灌胃12周。治疗结束取血生化检测血糖、血脂水平,放免法检测血胰岛素水平,HE染色光镜下观察肝脏组织的形态学改变,以RT-PCR法检测肝组织GR mRNA的表达水平,免疫组化法检测肝组织GR蛋白表达水平。结果：EGB可降低糖尿病大鼠血糖、血脂、血胰岛素水平,减轻肝细胞脂肪变性、坏死、炎细胞浸润,使肝组织GR mRNA的表达与蛋白表达明显减低。结论：EGB具有抑制2型糖尿病大鼠肝脏GR基因mRNA表达与蛋白表达的作用,这可能是其降低2型糖尿病大鼠血糖、血脂水平,改善肝内脂肪沉积的重要机制之一。     

蛋白酶体抑制剂MG132 对大鼠胶原诱导性关节炎的干预机制

目的：探讨蛋白酶体抑制剂MG132对大鼠胶原诱导性关节炎（Collagen induced arthritis,CIA）的干预效果及作用机制。方法：48只雌性SD大鼠被随机分为空白对照组、CIA模型组、MG132干预模型组,每组16只CIA模型组和MG132干预模型组注射牛Ⅱ型胶原建立CIA模型大鼠,初次免疫后第21天,干预组大鼠以1 mg/kg的剂量每天1次,连续14天皮下注射MG132。建模起每周观察大鼠关节肿胀程度,计算关节炎指数（Arthritis index,AI）,第42天后称重并处死大鼠;HE染色观察关节滑膜组织的病理改变;荧光底物测定法检测滑膜组织20S蛋白酶体的活性;蛋白质印迹法（Western blot）检测大鼠关节滑膜组织NF-κB/p65、IκBα蛋白的表达情况。结果：与CIA模型组比较,MG132干预模型组大鼠关节炎指数在注射MG132后一周明显降低（P<0.05）,关节滑膜组织未见明显增生,只伴有少量炎性细胞浸润。与空白对照组大鼠比较,CIA模型组大鼠关节滑膜组织20S蛋白酶体活性增高;与CIA模型组大鼠比较,MG132皮下注射干预后关节滑膜组织20S蛋白酶体活性降低（P<0.05）。与空白对照组比较,CIA模型组大鼠关节滑膜组织高表达NF-κB/p65蛋白,其中胞核NF-κB/p65表达增高更为明显（P<0.01）,注射蛋白酶体抑制剂MG132干预后,其滑膜组织胞浆及胞核NF-κB/p65蛋白表达均显著减少（P<0.01）。与空白对照组比较,CIA模型组大鼠关节滑膜低表达IκBα蛋白（P<0.01）,注射MG132干预后关节滑膜IκBα蛋白表达显著增多（P<0.01）。结论：大鼠CIA体内实验显示,蛋白酶体抑制剂MG132经皮下注射可明显改善大鼠关节炎症状,其作用机制可能与MG132降低大鼠CIA关节滑膜组织20S蛋白酶体活性,减少其底物蛋白IκBα的表达,从而抑制NF-κB活性有关。     

Microvesicular Fatty Liver in Rats with Resembling Reye's Syndrome Induced by 4-Pentenoic Acid

To produce an animal model of Reye's syndrome (RS), 20 adult male Wistar rats were given 10 repeated i.p. injections of 50 mg/kg 4-pentenoic acid (PA) each separated by an 8-h interval. Then, 90min after the tenth dose, they were given a final i.p. injection of 150 mg/kg PA. Thirteen control animals were injected with vehicle only using the same time schedule. More than half the animals in each group were fed a common diet, but the others were fasted during the terminal 10-h stage. All rats were sacrificed 30 min after the last injection. At the terminal stage, in comparison with the vehicle-injected controls, hypolipemia, hypoglycemia and high titers of serum ammonia and urea N were estimated significantly in the PA treated rats fed throughout the whole period. Hypolipemia and hypoglycemia were more prominent in the terminally fasted group than the group fed continuously. Only in the PA-treated rats fed throughout the whole period moderate morphological signs of microvesicular fatty liver were exhibited. Ultracytochemical findings and biochemical determinations showed that the major lipids in the microvesicular fatty livers were triglycerides. Morphometric analysis revealed distinct hepatic mitochondrial swelling in the PA-treated rats. Therefore, the above treatment with PA was able to induce microvesicular fatty liver in rats with resembling RS, which were fed throughout the treatment procedure, but not in the terminally fasted rats.     

Detection of aneuploidy by multicolor FISH in mouse sperm after in vivo treatment with acrylamide, colchicine, diazepam or thiabendazole

Multicolor fluorescence in situ hybridization (FISH) was used to investigate the induction of aneuploidy during meiosis in young adult male mice treated with chemicals chosen for the EU sponsored aneuploidy project (acrylamide, colchicine, diazepam and thiabendazole). The aim of the present study was to evaluate the frequency of aneuploid sperm induced by each of these chemicals by sperm FISH. Male (102/ElxC3H/El)F1 mice were treated with acrylamide (120 and 60 mg/kg single dose i.p.), colchicine (1.5 and 3 mg/kg single dose, i.p.), diazepam (300, 150 and 75 mg/kg single dose by oral intubation) or thiabendazole (100 and 300 mg/kg daily for 11 days by oral intubation). At 22 days after the last treatment, sperm were collected from the cauda epididymis. Three chromosome FISH was applied to determine hyperhaploid and diploid sperm with DNA probes specific for the chromosomes X, Y and 8. Five animals were treated per dose group and sperm aneuploidy was evaluated in 10,000 sperm per animal. We found significant increases in the frequency of total hyperhaploidy for the males treated with 3.0 mg/kg colchicine (0.092 versus 0.056%, P < 0.05) and with 1.5 mg/kg colchicine (0.082 versus 0.050%, P < 0.05), as well for the males treated with 300 mg/kg diazepam (0.081 versus 0.050%, P < 0.05), indicating that colchicine and diazepam each induced germ cell aneuploidy. We also found significant increases in the frequency of total diploidy for the males treated with 300 mg/kg diazepam (P < 0.05) and with 300 mg/kg thiabendazole (P < 0.05). No significant effects were found for 120 and 60 mg/kg acrylamide or for the other doses of diazepam and thiabendazole. These first results indicate that the multicolor FISH method is useful to determine aneuploidy induction in sperm of mice.     

5-Hydroxytryptamine-immunoreactive neurons and nerve fibers in the superior cervical ganglion of the rat

Indirect immunofluorescence method was used to localize 5-hydroxytryptamine-immunoreactive structures in the superior cervical ganglion of adult rats. In the ganglia of normal rats, 5-hydroxytryptamine immunoreactivity was localized in the small intensely fluorescent cells, but not in principal nerve cells. In the superior cervical ganglion of rats, pretreated with nialamide, a monoamine oxidase inhibitor, 150 mg/kg i.p., and the 5-hydroxytryptamine precursor, L-tryptophan, 45 mg/kg i.p., a large number of 5-hydroxytryptamine-immunoreactive principal nerve cells and small intensely fluorescent cells were detected. The immunoreactive principal nerve cells had long processes, and 5-hydroxytryptamine-immunoreactive nerve fibers were observed traversing the ganglion. In ganglia of rats pretreated with colchicine, occasional 5-hydroxytryptamine-immunoreactive principal nerve cells and several small intensely fluorescent cells were detected. Ligation of the main postganglionic nerve trunks of the superior cervical ganglion of normal rats resulted in the appearance of several 5-hydroxytryptamine-immunoreactive principal nerve cells and nerve fibers in the ganglion. To study whether the 5-hydroxytryptamine immunoreactivity in the superior cervical ganglion represented uptake or synthesis of 5-hydroxytryptamine, rats were injected with a specific 5-hydroxytryptamine uptake inhibitor, fluoxetine, 10 mg/kg i.p. twice a day for 5 days, and then they were treated with nialamide and L-tryptophan, as described above. In the superior cervical ganglion of fluoxetine-treated rats, a few 5-hydroxytryptamine-immunoreactive principal nerve and small intensely fluorescent cells, as well as some nerve fibers, were detected.(ABSTRACT TRUNCATED AT 250 WORDS)     

pifithrin-α抑制大鼠肝缺血再灌注早期PUMA蛋白的表达*

背景：pifithrin-α是一种可逆性p53抑制剂,应用pifithrin-α抑制p53通路对肝脏缺血再灌注损伤的影响尚不清楚。 目的：探讨核转录因子p53抑制剂对大鼠肝缺血再灌注后PUMA蛋白表达的影响。 方法：96只雄性Wistar大鼠随机分为对照组,缺血再灌注组,缺血再灌注+二甲亚砜溶媒对照组(二甲亚砜组),缺血再灌注+p53抑制剂pifithrin组(PFT组)。建立70%肝缺血模型,PFT组于60 min的肝血流阻断结束时立即给予pifithrin-α,二甲亚砜组给予等量二甲亚砜溶液,对照组和缺血再灌注组给予等量生理盐水。 结果与结论：大鼠肝缺血再灌注后1,3,6 h肝组织PUMA蛋白表达明显,PFT组可以明显抑制PUMA蛋白的表达,但缺血再灌注24 h PFT组PUMA蛋白的表达高于其他3组。结果可见pifithrin-α对肝脏缺血再灌注损伤有一定保护作用,其通过抑制p53从而诱导PUMA蛋白表达下调主要是在缺血再灌注早期。     

Ultrastructural changes of hepatocyte organelles induced by chemicals and their relation to fat accumulation in the liver

Fatty liver was induced in the rats shortly after administration of cycloheximide, ethionine, orotic acid, monensin or colchicine. It was strongly suggested that derangements in one or more of the hepatic lipoprotein metabolic steps, which occur at the levels of endoplasmic reticulum, Golgi apparatus and secretory vacuoles lead to an accumulation of triglyceride within hepatocytes.     

ULTRASTRUCTURAL CHANGES OF HEPATOGYTE ORGANELLES INDUCED BY CHEMICALS AND THEIR RELATION TO FAT ACCUMULATION IN THE LIVER

Fatty liver was induced in the rats shortly after administration of cycloheximide, ethionine, orotic acid, monensin or colchicine. It was strongly suggested that derangements in one or more of the hepatic lipoprotein metabolic steps, which occur at the levels of endoplasmic reticulum, Golgi apparatus and secretory vacuoles lead to an accumulation of triglyceride within hepatocytes.     

Effect of dl-ethionine and Naturally Occurring Amino Acids on Adrenal Necrosis Induced by 7,12-dimethylbenz[a]Anthracene and its 7-Hydroxymethyl Derivative in Female Sprague-Dawley Rats

dl-Ethionine at a dose of 125 mg. i.p. 3 days and, to a lesser extent, 4 days before i.v. treatment with 3 mg. 7,12-dimethylbenz[a]anthracene (DMBA) protects the adrenal glands from the adrenocorticolytic action of the polycyclic hydrocarbon in female Sprague-Dawley rats. Treatment of rats less than 3 days or more than 4 days before DMBA challenge has no protective effect. dl-Methionine at the same dose as ethionine is not protective when given 3 days before DMBA but shows some protective action as a 1-day pretreatment.The protective action of ethionine seems unrelated to the suppression of protein synthesis or to the production of fatty liver. With both methionine, and ethionine, protection of adrenal glands is correlated with the marked vacuolation of the cytoplasm of hepatocytes.Administration of methionine at the same dose as ethionine abolishes the protective action of the latter when they are given 3 days before DMBA.Glycine, like methionine, also protects when given from about the same time as DMBA to 24 hr. beforehand. Its protective action can be prevented by concomitant administration of large doses of arginine.None of the aforementioned protective treatments were effective against adrenal necrosis induced by 7-hydroxymethyl-12-methylbenz[a]anthracene.     

The influence of daunomycin on development of Yoshida sarcoma after nonspecific stimulation of the immunologic system.

Injection of BCG in rats inoculated with Yoshida sarcoma had no influence on the development of the tumor or survival time of the rats in comparison with the control group. On the other hand, survival time was increased more than threefold in a group of rats injected with daunomycin in a single dose of 1 mg/kg i.p. Longest survival and lowest mortality were observed in a group of rats treated with daunomycin and BCG, in which survival time was six times longer than in the controls, and mortality after 50 days was 30% lower, and after 100 days even 50% lower than in the group of rats that were treated only with daunomycin.     

New property of the heparin-serotonin complex

The antihypoxic activity of the heparin-serotonin complex was studied under conditions of acute hypobaric hypoxia. Rats were given an intraperitoneal injection of the complex in a dose of 300 μg/kg and “lifted” on a height of 12,000 m. In these rats, the intervals before the posture loss and the second agonal inhalation were 9.6- and 8.8-fold as long as those in control rats. The survival of the complex-treated rats was 90%, 70% in rats injected with heparin or serotonin, and 50% in the control group. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10. pp. 425–427, October, 1998