Prostaglandin synthesizing enzyme activities of hepatocytes and non-hepatocytes in rat liver as a function of age

The developmental profile of prostaglandin (PG)-synthesizing enzymes in liver was investigated in rats from the fetus to 2 years old. In the neonatal period, the activities of PGD2-(2.7 nmol/min/mg protein) and PGE2-(2.2 nmol/min/mg protein) synthesizing enzymes were predominant, whereas PGE2-synthesizing enzyme alone further increased in activity during adult to old ages (5.2-6.1 nmol/min/mg protein). In order to determine the sites of PGs production in rat liver, we prepared hepatocytes and non-hepatocytes by a collagenase digestion method. Regardless of the ages we examined, the major PG produced in the hepatocytes was proved to be PGE2, on the other hand, PGD2 was almost exclusively produced in the non-hepatocytes. These results suggest that each PG may have individual roles in the development of rat liver.     

Differential effects of placental lactogen,growth hormone and prolactin on rat liver ornithine decarboxylase activity in the perinatal period

Ovine placental lactogen, (oPL), ovine growth hormone, (oGH), and ovine prolactin, (oPRL) are present in high concentrations in the fetal circulation late in gestation. To determine if these hormones stimulate the activity of ornithine decarboxylase (ODC), an enzyme widely implicated in the control of cellular growth, rat fetuses were injected $\text{in utero}$ with 100 μg of oPL, oGH, oPRL, rat growth hormone (rGH) or rat prolactin (rPRL) and ODC activity in the livers, hearts, and brains of the fetuses was measured 2, 4, and 6 hours after injection. OPL stimulated fetal liver ODC activity by 282 ± 45% (mean ± SEM) as compared to litter mates injected with buffer alone but oGH, oPRL, rGH and rPRL had no effect on fetal liver ODC activity. However, in neonatal rats 24–48 hours old all five hormones significantly increased liver ODC activity. ODC activities in the hearts and brains of the fetuses and neonates were unaffected by any of the five hormones. In other experiments 50 μg of oPL significantly stimulated fetal liver ODC activity while 250 μg of oGH were without effect. However 25 μg of oGH significantly stimulated liver ODC activity in rat pups 1–2 days after birth. These results suggest that oPL, by its stimulation of ODC activity, has somatotropic effects in the fetus and that rat liver ODC activity becomes responsive to growth hormone and prolactin in the perinatal period.     

Ovine placental lactogen stimulation of ornithine decarboxylase activity in brain and liver of neonatal rats

Ovine placental lactogen (oPL), growth hormone (oGH), prolactin (oPRL) and human placental lactogen (hPL) were administered intracisternally (ic) or intraperitoneally (ip) to 17 day old rats and brain and liver ODC activities determined four hours later. When given ic, oPL, oGH and oPRL caused significant increases in brain ODC activity, while hPL had no significant effect. After ip administration, oPL and oGH also caused a significant increase in brain as well as liver ODC activity but oPRL and hPL were without significant effect. The stimulation of polyamine metabolism by oPL together with earlier reports of its potent somatotropic effects and its high concentration in the fetus supports the hypothesis that oPL may be important in the regulation of fetal growth.     

Alterations in the activities of rat tissue hexose monophosphate dehydrogenases in response to premature weaning and dietary restriction at mid-lactation

Summary The activities of the hexose monophosphate dehydrogenases increased in adipose tissue, remained unchanged in liver and decreased in mammary gland following the weaning of rats at mid-lactation (day 14). When dietary intake was restricted at mid-lactation, the activities of the hexose monophosphate dehydrogenases increased in adipose tissue, decreased in liver, but were unaltered in mammary gland. Premature weaning on day 14 postpartum resulted in maternal increases in both plasma insulin and glucose, which peaked at day 16. The plasma insulin levels decreased from day 14 to day 18 postpartum in the normal lactating rat, and a similar trend was observed for animals on a restricted dietary intake. Daily food consumption in the lactating rat decreased from 50 g to 20 g after premature weaning. The live weight of pups raised on dams given a restricted food intake from day 14 had decreased by day 17 postpartum, whereas an increase in daily live weight gain was recorded for the litters from the lactating controls. The results demonstrate that the activities of the hexose monophosphate dehydrogenases are regulated differentially between tissues of the lactating rat.     

Survey of fructose 1,6-bisphosphatase isoenzyme in rat organs and ontogenic expression of the enzyme in rat fetus

1. Among eleven tissues of rat, the liver type of fructose 1,6-bisphosphatase (FBPase) subunit was detected in the liver, kidney, testis, pancreas and lung by Western blot analysis using anti-(liver FBPase) or anti-(muscle FBPase) serum. 2. The muscle type of the enzyme subunit was detected only in the pancreas other than skeletal muscle. Both types of the enzyme subunit were found in the pancreas. 3. Neither anti-(liver FBPase) nor anti-(muscle FBPase) serum detected the band of enzyme subunit on the blots of the extracts of brain, heart, small intestinal mucosa, spleen and placenta. 4. FBPase is present in fetal rat liver at least as early as the 14th day of gestation. 5. In agreement with the increase in immunological staining density, the level of the enzyme activity in fetal liver increased exponentially during fetal development. 6. The muscle enzyme was not detected until the fetus reached the 19th day of gestation.     

Effect of maternal iron deficiency on GABA shunt pathway of developing rat brain

Iron deficiency during pregnancy and lactation (35 mg iron/kg diet) produced a significant reduction in liver nonheme iron in dams as well as in fetus and young ones. The body, liver and brain weights of fetus, new-born, and developing pups remained unaffected. However, the body weight and PCV were reduced only in 21-day-old pups. The enzyme activities of GDH, GAD, GABA-transaminase, and NAD(+)-linked ICDH were reduced in 14 and 21-day-old pups. The enzyme activities of NADP(+)-linked ICDH activities remained unaffected in the fetus and developing pups brain. Maternal rehabilitation on iron sufficient diet for 1 week from day 14 to 21 of lactation period did not reverse these changes. The maternal iron deficiency during lactation period alone did not cause any alteration in all parameters assayed, however, there was a reduction in liver non-heme iron of pups on days 14 and 21.     

Cytofluorimetric study of the content of glycogen and its fractions in rat liver cells in the course of the 1st week of postnatal ontogeny]

A cytofluorometric study of the total glycogen and its fractions in rat liver cells using the fluorescent PAS reaction was made during 1--7 days of the postnatal development. It was established that glycogen content was small on the first two days of development. The glycogen content increases only on the third day after birth. The glycogen of the rat liver cells during a first week of the postnatal development is different from that detected in adult liver cells in two aspects: in 3 day old hepatocytes soluble and stable glycogen fractions are equal, while in adult rat liver cells the former makes 80--90%; during the first week of the postnatal development, the stable fraction of rat liver cell is more labile, while in the adult rat liver the soluble fraction of glycogen is more labiles.     

Mechanisms of the disorder of the hormonal regulation of plasma membrane adenylate cyclase in the rat liver during early ontogeny under in vitro irradiation

Possible reasons for the previously detected inhibitory effect of gamma-radiation (100-1000 Gy in vitro) on isoproterenol-stimulated activity of adenylate cyclase (AC) of the liver plasma membranes of a 20-day-old rat fetus were investigated. It was discovered that the number of beta-adrenergic receptors was reduced. Analysis of basal and fluorine-stimulated activities of AC attests to the radiation-induced damage to catalytic and N-regulatory proteins. The radiation-induced derangement of membrane lipids, where AC functions, is shown.     

模拟急性高原低氧对妊娠大鼠及其胎儿,新生儿肝细胞与溶酶体的影响

低气压舱模拟海拔8000m24h。观察对不同期妊娠大鼠、胎儿及新生儿肝溶酶体酶血清转氨酶、肝糖原、蛋白质和总脂水平的影响。证明:22天孕鼠肝细胞及其溶酶体损伤程度比16天孕鼠和非孕鼠严重;对16天和22天胎儿鼠肝溶酶体无明显影响,显示了胎儿肝溶酶体低氧下的高稳定性和母体对胎儿的保护作用;新生儿鼠肝细胞溶酶体对低氧的耐受性明显高于孕鼠与非孕鼠。低氧使孕鼠、胎儿、和新生儿鼠肝细胞糖原含量明显降低。新生儿诞生后肝糖原贮备极度消耗,低氧加剧这种作用。随着胎儿发育,肝蛋白质含量渐增,低氧导致全肝蛋白质量减少。无论孕鼠与非孕鼠,低氧造成肝总脂水平增高。     

The development of carnitine synthesis from γ-butyrobetaine in the rat

The ability of the rat liver to synthesize camitine from γ-butyrobetaine increases from low values in the fetus to adult values on the 8th day after birth. The rate of synthesis of camitine is greater when determined in the high-speed supernatant than in the low-speed supernatant of the liver. No synthesis could be shown to occur in neonatal rat kidney or neonatal brown adipose tissue.     

大白鼠DNA拓扑异构酶Ⅰ生物学性质的研究

对大白鼠组织作DNA拓扑弄构酶Ⅰ(拓扑酶Ⅰ)活力测定,见酶活力出现在胚胎早期,在胚胎发育过程及出生后不同年龄期,酶活力基本稳定;几种成年大鼠组织的酶活力彼此无显著差异;肝细胞再生及癌变,酶活力亦无显著变化。     

Absorption by rat fetal tissues of 14C-labeled phospholipids injected into the rat body in the late stages of pregnancy

The authors studied the possibility of 14C-phospholipid transplacental penetration after 15C-phospholipid injection into rats at the 20th day of pregnancy. The preparation of 14C-phospholipids (total phospholipids) was isolated by thin-layer chromatography from the liver of rats injected with 2-14C-sodium acetate. One hour after its injection into the rat, 14C-phospholipids were detectable in total phospholipids of the pulmonary and cerebral fetal tissues. It was discovered that specific radioactivity of phospholipids contained by these tissues was 2--5 times higher when 14C-phospholipids were injected subcutaneously as compared with intramuscular injection. It is concluded that exogenous phospholipids entrapped in the mother's circulation penetrate the placental barrier of the fetus and the blood-brain barrier of the mature fetus, being consumed by different fetal tissues for forming membrane structures of the fetal tissues.     

阻断子宫动脉建立FGR大鼠模型的研究

目的通过暂时阻断妊娠期大鼠子宫血供的方法建立子宫缺血引起胎儿生长受限的动物模型。方法根据大鼠子宫动脉是卵巢动脉的一个分支的解剖特点,于孕鼠妊娠第15天时施行手术暂时阻断卵巢动脉并于第21天行剖宫产术,术后称量新生胎仔体重及胎盘、脑、心、肝、肺、肾等重要脏器重量,对比各组间新生胎仔的预后的不同,并对照研究阻断血供10、20、30及40 min对胎仔的不同影响。结果妊娠晚期阻断孕鼠卵巢动脉20min可成功构建胎儿生长受限模型,这种方法与阻断动脉血流30或40 min相比,手术时间短,技术要求不高,胎仔死亡率与对照组差异无显著性(P>0.05)。各实验组较对照组新生胎仔体重及胎盘、各重要脏器重量均明显降低(P<0.05)。结论通过阻断卵巢动脉从而阻断子宫动脉血流,成功建立缺血缺氧性FGR孕鼠模型。该模型重复性好,操作简便,并可成功设立同体对照,为进行FGR相关的产科理论研究提供了一个有利的技术平台。     

Isolation, characterization, and expression of fatty acid binding protein in the liver of Gallus domesticus

1. Fatty acid binding protein (FABP) was isolated from chicken liver cytosol. 2. Apparent molecular weight, pI, functional activity, and hybridization of a rat hFABP cDNA probe with chicken liver mRNA suggest that chicken liver FABP is structurally related to hepatic FABP (hFABP) previously isolated and characterized in the rat. 3. Fatty acids bound to liver FABP affect the electrophoretic nature of FABP. 4. Levels of liver FABP mRNA isolated from chickens at various stages of development parallel developmental alterations in lipid metabolism, being highest in day old chicks and laying hens versus juvenile birds.     

Role of alpha-tocopherol in cadmium-induced oxidative stress in Wistar rat's blood, liver and brain

Cadmium (Cd) a highly toxic metal is considered to be a multitarget toxicant, and it accumulates principally in the liver and kidney after absorption. In vivo studies of mouse and rat liver have shown that apoptosis plays a primary role in Cd-induced hepatotoxicity. However, the detailed mechanisms by which toxic metals such as Cd produce their effects are still largely unknown. The present study aimed at investigating the consequences of exposure to Cd, alpha-tocopherol and their combination on stress biochemical parameters (lipoperoxidation and protein carbonyls levels). Male albino Wistar rats (1 month old) were treated intravenously with cadmium (2 mg CdCl(2)/kg body weight/day), and alpha-tocopherol (100 mg/kg body weight/day), or with alpha-tocopherol+Cd (100 mg Vit E/kg body weight, 2 mg CdCl(2)/kg). The lipoperoxidation was measured by the thiobarbituric acid reactive substances (TBARS) method and oxidatively generated damage to proteins by determining carbonyl (DNPH) levels. Among the hematological parameters measured the haematocrit value and haemoglobin concentration were significantly decreased in the blood of Cd-treated rats. A significant increase was observed in the level of malondialdehyde (MDA) and protein carbonyls in the cadmium exposed group compared to control group (p<0.001), and these values were decreased after administration of alpha-tocopherol (group 4). The activity of lactate dehydrogenase in rat liver and brain showed a significant increase as compared to that found in the control group and significant decrease of catalase and superoxide dismutase activities. In the liver of the Cd-treated group the contents of reduced glutathione were decreased. Our results suggest that cadmium induces an oxidation of cellular lipids and proteins and that administration of alpha-tocopherol can reduce Cd-induced oxidative stress and improve the glutathione level together with other biochemical parameters.     

Structural changes of liver microsomes in rat during neonatal life: influence on the glucuronidation rates of various substrates

The Vmax of the membrane bound UDP-glucuronosyltransferase (UDP-GT) towards group 1 substrates (4-nitrophenol, 2-naphthol) was particularly higher in young rats than in adults. On the contrary, activity towards group 2 substrates such as borneol or testosterone was not detectable in fetus liver. The developmental pattern of UDP-GT was related to changes in lipid composition of microsomes, namely in the content in lysophosphatidylcholine which rose at birth. The phospholipid-cholesterol molar ratio also increased 2 fold from the 16th day of fetal life to the 4th day after birth. Measurement of the steady state anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) as well as determination of the order parameter S and the rotation cone angle of the fluorescent probe strongly suggested an increase in membrane fluidity in rat liver microsomes during ontogenesis.     

A microtubule-associated protein (MAP1) which is expressed at elevated levels during development of the rat cerebellum.

Monoclonal antibody (MAb) G10 labels a single high mol. wt. (HMW) band on Western blots of microtubule preparations from 2 day old rat brain. The G10 antigen is thermolabile and co-migrates with microtubule-associated protein (MAP)1 from young rat brain on low percentage (5%) polyacrylamide-SDS gels. The G10 antigen decreases by about five times from birth to adulthood in the rat cerebellum. The same single band is labelled on Western blots of homogenates of whole neonatal rat brain but no labelling is found using neonatal or adult kidney, lung or liver. We have therefore identified a brain-specific MAP1, designated MAP1(x). Immunofluorescence microscopy using MAb G10 on parasagittal sections of rat cerebella shows labelling of the newly formed molecular layer in 6 day old rats. Only a narrow band close to the pial surface is labelled in 18 day old animals, which disappears in the adult. Labelling of the cerebellar white matter found in young rats also disappears. Neurones but not flat cells in cerebellar cultures label with MAb G10. All staining patterns are consistent with an axonal distribution of the antigen. MAP1(x) may be part of a developmentally regulated microtubule structure.     

Ontogeny of Nk-1+ natural killer cells. I. Promotion of Nk-1+ cells in fetal, baby, and old mice

Using anti-Nk-1.1 serum, the alloantiserum specific for murine natural killer (NK) cells, we followed the ontogenetic development of Nk-1+ cells in fetal thymus, liver, and spleen. A transient population of Nk-1+ cells in fetal thymus was observed on day 14 but not on day 16 of gestation. On day 16 of gestation, Nk-1+ cells were detected only in liver and spleen. The proportion of Nk-1+ cells in spleen remained high (20 to 30%) at birth and persisted until 2 to 3 wk old. The Nk-1+ cells in "baby" (1 to 2 wk old) spleen bound to YAC cells but failed to lyse them in 51Cr-release assay. Upon induction with interferon (IF), the proportion of Nk-1+ cells increased, but the lytic activity remained low, suggesting that the "baby" NK-1+ cells are immature in lytic function. In old mice (12 to 14 mo), Nk-1+ cells were also detectable, even though NK activities were lower compared with those of the young adult (6 to 8 wk old) mice. The Nk-1+ cells of old mice were readily induced by IF to exhibit activities, and the induced NK cells were Nk-1+. We have thus established Nk-1.1 antigen as an early hemopoietic differentiation antigen. Splenic Nk-1- cells could be induce by IF to become NK-1+ cells, which could be inactive or active in NK assays, dependent on the age of the mice.