Effects of Concanavalin A on the isolated perfused rat liver

Summary In the isolated perfused liver, Concanavalin A provoked a significant decrease of flow rate within 2 to 4 min which was dose-dependent and could be partly inhibited by specific antagonists.Furthermore it was found that the lectin led to a decline of the respiration, an increase of the lactate/pyruvate ratio and a release of the transaminases into the medium. It was suggested that Concanavalin A displaced endothelial cells in the liver capillaries, which occluded the vessels and decreased the flow rate. The decreased respiration was considered to be secondary to this effect.     

硫代乙酰胺诱导大鼠肝纤维化的研究

目的研究硫代乙酰胺对大鼠肝纤维化模型的诱导作用。方法采用0．03％的硫代乙酰胺腹腔注射,每周2次,构建大鼠肝纤维化模型;观察大鼠肝纤维化形成情况。结果与空白组比较,模型组大鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、透明质酸（HA）明显升高（P〈0．01）;层粘连蛋白（LN）升高（P〈0．05）。组织病理提示模型组大鼠肝细胞大量坏死,假小叶形成。结论硫代乙酰胺能诱导大鼠形成肝纤维化。     

The effect of chronic adriamycin treatment on heart kidney and liver tissue of male and female rat

The influence of chronic adriamycin treatment on cellular defence mechanisms against free radicals has been determined in rats. To that end, the changes in vitamin E content, activity of superoxide dismutase, catalase and factors of the glutathione system were measured in heart, kidneys and liver after 24 and 52 days of treatment. Moreover, damage was assessed by measuring the activity of NADPH- and NADH-cytochrome c reductase. The results concerning the components of the oxidative defence systems in male rats showed reductions in the activity of superoxide dismutase and catalase in renal tissue and in factors of the glutathione system in liver tissue. In cardiac tissue an increased activity of catalase and elevated content of total glutathione were found. Vitamin E content was increased in liver and to a lesser extent, in kidneys. The activity of Se-dependent glutathione peroxidase sharply decreased only in liver. Major differences between male and female rats were not observed in renal and cardiac tissue, as far as protective factors were concerned. However, a decrease in catalase activity was detectable earlier in male kidneys. The protective factors in liver of female rats were far less susceptible to in vivo treatment with adriamycin, as compared to liver of male rats. Decreased activity of the cytochrome reductases was found in liver of male rats. In male renal tissue only cytochrome c reductase activity was significantly reduced. Male cardiac tissue showed no signs of biochemical damage, although from histological examination in a parallel study [J Natl Cancer Inst 76: 299–307 (1986)] lesions were evident. In female rats no damage was found in liver, kidneys and heart.     

Action of lead on the cationic balance in the perfused rat liver

Summary Lead augments potassium release from perfused rat livers to a much lower extent than from red cells. In contrast mercurials increase cationic permeability of red cells and liver cells to a similar extent. Data from liver perfusions were compared with earlier findings on red cells reported by Passow.This work is supported by the Deutsche Forschungsgemeinschaft.     

The effect of p,p'-DDT (dicophane) and its main metabolites on the respiration of rat liver mitochondria

The effects of DDT, DDE, DDOH and DDA on the oxidation of NADH, glutamate, -hydroxybutyrate and sucoinate by rat liver mitochondria were investigated. The influence of these compounds on the activity of purified liver glutamate dehydrogenase was also checked. It was found that DDT and all those of its metabolites investigated inhibited oxidation of NAD-linked substrates by both intact and sonicated mitochondria. The water-soluble metabolites of DDT (DDOH and DDA) stimulated succinate oxidation by intact but not by sonicated mitochondria, and inhibited the activity of glutamate dehydrogenase. It is concluded that DDT and its metabolites may affect mitochondrial respiratory chain between NADH and CoQ, inhibit glutamate dehydrogenase, and uncouple oxidative phosphorylation.     

Phalloidin poisoning of the isolated rat liver at 40°C

Summary The first effect of phalloidin on the potassium content of the isolated liver is a small potassium uptake or a decrease of the spontaneous potassium release. This occurs at 40°C as well as at 27°C. At 40°C the potassium release due to phalloidin starts 14±3 min after the toxin has come in contact with the liver, while the increase of the weight, of the light scattering, and of the oxygen consumption of the liver start 10–12 min earlier.     

Similarity between the effect of experimental congestion of the isolated perfused rat liver and the action of cytochalasin B

Summary Livers of rats were perfused with dextran solutions, containing no red cells. Changes in the dextran concentration due to water shifts between the intra- and extracellular space of the liver were recorded continuously by polarimetric measurement. Cytochalasin B causes an uptake of potassium and water, followed by a release of water and a spontaneously reversible release of potassium, while the liver weight increases. From these effects an uptake of dextran, probably by an endocytotic process, is concluded.     

The effect of p,p′-DDT (Dicophane) and its metabolites on ATPase activity in rat liver mitochondria

The effect of DDT and its main metabolites on ATPase activity in rat liver mitochondria was studied. These compounds stimulated ATPase activity in intact mitochondria of rat liver and had no effect on ATPase activity in damaged mitochondria. This suggests that the uncoupling of the oxidative phosphorylation in mitochondria may be responsible for the toxic effect of DDT in mammals.

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Abbreviations Used DDT or p,p-DDT 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane - DDE 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene - DDOH 2,2-bis (p-chlorophenyl)ethanol - DDA bis (p-chlorophenyl)acetic acid - DNP 2,4-dinitrophenol - ATPase ATP phosphohydrolase (EC 3.6.1.3.)     

Metabolism of metyrapone by a soluble enzyme system in rat liver

Summary The formation of a metabolite of metyrapone by an oxygen sensitive soluble enzyme system in rat liver 105,000×g supernatant has been demonstrated. Enzyme activity requires the intact keto function of metyrapone.The experiments were carried out with the financial support of the Deutsche Forschungsgemeinschaft, Bad Godesberg, Germany.The valuable technical assistance of Miss Ingeborg Raab is gratefully acknowledged.     

Effects of chlorinated paraffins on rat liver microsomal activities and morphology

Short term effects of chlorinated paraffins with different length of the carbon chain and different degree of chlorination were investigated with respect to rat liver cytochrome P-450 mediated metabolism and liver cell morphology. When paraffins were administered by i.p. injection liver weights increased inversely with the length of the carbon chain. The short carbon chain paraffins with a high degree of chlorination increased the concentration of liver microsomal cytochrome P-450, inhibited the metabolism of 7-ethoxyresorufin but increased the metabolism of benzo(a)pyrene, especially the formation of the 4,5-diol metabolite. Short carbon chain paraffins gave rise to a proliferation of the smooth ER, increased the number of cytoplasmic fat droplets as well as the number and size of mitochondria and peroxisomes and finally induced the occurrence of autophagosomes and lysosomes. The fat droplets were preferentially degraded in lysosomes. In all respects the long carbon chain paraffins were less biologically active.     

齐墩果酸钠盐对大鼠化学性肝损伤的保护作用

目的 观察齐墩果酸钠盐对化学性损伤的肝细胞保护作用。方法 采用CCl4亚急性染毒建立化学性肝损伤大鼠模型,用齐墩果酸钠盐每天按三个剂量(3mg／kg、15mg／kg、30mg／kg)喂食大白鼠30天,测其血液生化指标并作组织病理学检查。结果 与对照组比较,齐墩果酸钠盐能显著降低大鼠血清的ALT和AST活性．肝脏组织结构病理损伤明显改善。结论 齐墩果酸钠盐对亚急性OCl4损伤的肝细胞具有保护作用。     

N-亚硝基二乙胺(DEN)诱导SD大鼠肝癌模型的研究

目的 建立与人类的肝癌发生发展过程相似的动物模型,以便研究肝癌的发生发展过程。方法 取体质量120~150 g雄性SD大鼠65只,适应环境1周后随机分为实验组(50只)和对照组(15只),实验组饮用含N-亚硝基二乙(DEN)(浓度为76 ppm)(以下简称DEN)的水连续6周后停药,改自由饮水3周,再继续饮用含DEN(76 ppm)的水至20周。对照组常规自由饮水。结果 病理学检查证实DEN可诱发大鼠形成肝癌,14周后成癌率为66.7%(10/15),大鼠肝癌的癌变过程大致可分为肝炎期、肝硬化期和肝癌期三个发展阶段。结论 饲以76 ppm剂量DEN可诱发大鼠肝癌模型的建立,可以为我们研究大鼠肝癌的发生发展过程提供可靠的动物模型。     

Effect of chronic treatment of haloperidol on the rat liver: a stereological and histopathological study

Haloperidol is commonly used in therapy for patients with acute and chronic schizophrenia. Because it can have some adverse effects on specific target organs such as the liver, we analyzed whether haloperidol exerts a toxic effect on rat liver by means of stereological and histopathological methods. Fifteen adult male rats, divided into three groups, were used in the experiments. Once a day for 6 weeks, either saline or 0.4 or 0.8 mg kg⁻¹ doses of haloperidol were given interperitoneally to the control, low-dose, and high-dose groups, respectively. At the end of the experiment, rats were killed by an overdose of a general anesthetic, and the livers were dissected out, fixed for sectioning, and evaluated using stereological and histopathological methods. Hepatocyte numbers were found to be 271.672, 291.072, and 238.415 hepatocytes per cubic millimeter in the liver of the control, low-dose, and high-dose groups, respectively. The differences between high-dose and control groups and also between high-dose and low-dose groups were significant (p < 0.05). Our histopathological findings at both the structural and the ultra-structural level were confirmed by stereological estimations. Results suggest a relationship between haloperidol dose and toxic effects on the liver, and they indicate that a high dose of haloperidol may result in irreversible liver damage. This research was conducted in the Laboratory of Pharmacology at Ataturk University, School of Medicine, 25240 Erzurum/Turkey and the Laboratory of Histology and Embryology, School of Medicine, at Ataturk University, 25240 Erzurum/Turkey. None of the authors has a commercial interest, financial interest, and/or other relationship with manufacturers of pharmaceuticals, laboratory supplies, and/or medical devices or with commercial providers of medically related services.     

肝移植大鼠术后补充适量碱性液体对术后存活率的影响

目的 探讨术后补充适量的碱性液体对全肝移植术大鼠术后存活率的影响。方法将40只进行全肝移植的受体SD大鼠（以供肝复通后有胆汁排出、关腹时吻合口无活动性出血及术后苏醒为标准）随机分为A、B两组，各20只，A组术后不予补液，B组术后给予4ml碳酸氢钠和生理盐水混合溶液静脉补液。结果 B组大鼠术后迅速苏醒并很快恢复正常的饮食和排泄，术后24h存活率也明显优于A组（A组14只存活，存活率为70％；B组19只存活，存活率为95％）。结论 大鼠全肝原位移植术后补充适量的碱性液体有利于纠正机体酸中毒，迅速恢复血容量，纠正低压状态，减少血栓的发生率，能明显改善受体大鼠术后一般情况，对提高肝移植大鼠术后的存活率有一定的积极作用。     

Alteration of rat liver microsomal monooxygenase activities by gasoline treatment

Previous work has shown an increase in rat liver enzyme activities after chronic exposure to gasoline vapor. In the present study, male Sprague-Dawley rats were pretreated with unleaded gasoline at 1 and 5 ml/kg, i.p., and selected hepatic microsomal monooxygenase activities were determined at 18, 48, and 72 h. At 18 h, moderate increases were observed in P450 content (1.3-fold), cytochromec-reductase activity (1.25-fold), and inN-nitrosodimethylamine demethylation rate (1.25- to 1.6-fold). Pentoxyresorufin dealkylase activity (an activity displayed primarily by P450IIB1) was significantly elevated at 18 and 48 h (30- to 60-fold), and ethoxyresorufin dealkylase activity (an activity displayed by P450 IA1) was elevated (2- to 4-fold). Immunoblot analysis revealed no change in P450IIE1 at these time points, but an elevation in P450IIB1 in agreement with the pentoxyresorufin dealkylase activity measurements.This study was supported by National Institutes of Health Grant ES 03938 and Grant 88B18 from the American Institute for Cancer Research     

The effects of dietary selenium on cadmium binding in rat kidney and liver

In acute studies, approximately 70–90% of cytosolic cadmium in liver and kidney has been shown to be bound to metallothionein, a low-molecular weight protein. In this study, we report on the influence of dietary selenium on the distribution of cadmium in rat kidney and liver. Contrary to the findings of most acute studies, our results indicate that only a relatively small proportion of cadmium (approximately 14% in the kidney and 44% in the liver) is bound to metallothionein when cadmium is administered for 7 weeks in the diet and via osmotic minipumps to selenium-deficient rats. Feeding rats the same diet supplemented with 1.0 ppm selenium results in no detectable cadmium-metallothionein peak in the kidney, and only about 10% of the cytosolic cadmium elutes as cadmium bound to metallothionein in the liver. In animals fed the selenium-supplemented diet, the bulk of the cadmium is recovered in the low-molecular weight fraction. Dietary selenium did not significantly affect the distribution of zinc and copper in the kidney or liver.Supported by NIEHS Center Grant ES-00159 and a grant from the Selenium — Tellurium Development Association     

肝硬化对大鼠和病人血锰等6种金属含量的影响

目的探讨肝硬化对血锰(Mn)等6种金属含量的影响,为临床上阐明肝硬化所致金属元素代谢紊乱的并发症提供科学依据。方法将20只大鼠随机分为肝硬化组和正常对照组,每组10只;另观察52例肝硬化病例及44例非肝硬化对照者,采用电感偶合等离子发射光谱法测定大鼠和病人血锰(Mn)、锌(Zn)、铜(Cu)、铁(Fe)、钙(Ca)和镁(Mg)含量。结果肝硬化大鼠全血Mn、Zn、Cu、Ca的含量明显高于正常对照组(P<0.05~P<0.01),而Fe含量明显低于正常对照组(P<0.05)。肝硬化病人血Mn含量为(1.45±1.27)μmol/L,明显比非肝硬化病人的(0.36±0.18)μmol/L高(P<0.01);Zn、Fe和Mg含量分别为(74.46±17.23)(、6 507.50±1 413.03)(、1 005.83±157.50)μmol/L明显低于非肝硬化病人(P<0.01)。结论肝硬化时,大鼠和病人血Mn等6种金属的含量是受到不同程度的影响。因此,在临床上检测肝硬化病人血液上述金属的含量,可能有益于防止因肝硬化所致某些金属缺乏和(或)过多所引起的并发症,具有重要的临床毒理学意义。     

Chronic intoxication with acetaldehyde stimulates collagen biosynthesis in rat liver

It was found that chronic intoxication of rats with acetaldehyde results in a distinct, progressive increase of 5³H-proline incorporation into collagen synthesized by liver. At the same time, biosynthesis of other proline-containing (noncollagenous) proteins does not change significantly. The effects are similar to those induced by chronic intoxication of rats with ethanol. Since acetaldehyde is an intermediary metabolite formed during ethanol oxidation in liver, it may be concluded that acetaldehyde is a factor responsible for alcohol-induced liver fibrosis.     

Induction of monooxygenases and growth in rat liver by progesterone

Female Wistar rats were treated with various doses of progesterone orally via the diet or via the SC route. Oral treatment resulted in enhanced progesterone levels in the liver as measured by radioimmunoassay. There were up to 3-fold increases in activity of ethylmorphine demethylation by isolated microsomes; metabolism of aminopyrine and benzphetamine was less enhanced, that of aniline and P-nitroanisol showed no distinct increases. Progesterone also caused increases in liver size and total liver protein by up to 50%; total liver DNA showed only slight, insignificant increments. These studies suggest that hepatic effects of progesterone are similar to those previously described with synthetic steroids such as pregnenolone-16-carbonitrile (PCN) and cyproterone acetate.Abbreviations A aniline - AP aminopyrine - BPA Benzphetamine - CPA cyproterone acetate - EM ethylmorphine - PCN pregnenolone-16-carbonitrile - p-NA P-nitroanisole