VARIATION OF THE ENZYMES OF THE UREA CYCLE AND ASPARTATE TRANSCARBAMYLASE IN LIVER OF PREGNANT RATS

1967 ◽  
Vol 45 (9) ◽  
pp. 1371-1374 ◽  
Author(s):  
A. Roberge ◽  
R. Charbonneau ◽  
L. Berlinguet

The variations in the specific activities of the enzymes of the urea cycle were studied in the livers of pregnant rats and also in the livers of male rats and other females with the same body weight. The specific activities of the five enzymes of the urea cycle are the same in male and in female except for argininosuccinase. The activity of this enzyme is twice as high in female rats as in male rats. In pregnancy, the activities of the enzymes of the urea cycle are decreased except for arginase, which increases. Aspartate transcarbamylase remains constant during the same period.These results lead to the supposition that another pathway for the synthesis of orotic acid may exist, or more probably that there exist two carbamyl phosphate synthetases, one for pyrimidine biosynthesis and one for urea synthesis.

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.


2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.


2010 ◽  
Vol 29 (4) ◽  
pp. 372-379 ◽  
Author(s):  
Xiao-bo Hu ◽  
Yi Gong ◽  
Lei Li ◽  
Shao-ping Nie ◽  
Yuan-xing Wang ◽  
...  

The acute toxicity of zinc threoninate chelate was assessed. The oral lethal dose 50% (LD50) was 2710 mg/kg in female rats and 3160 mg/kg in male rats. Genotoxicity was assessed by Ames test in Salmonella typhimurium strains TA97, TA98, TA100, and TA102, by bone marrow mouse micronucleus test and a sperm abnormality test with mice. Thirty-day repeat dose toxicity study was conducted at oral daily doses of 0, 42, 169, and 675 mg/kg in rats. Teratogenicity was assessed at the same daily dose in pregnant rats by gavage. No significant changes in body weight, food consumption, organ weight, relative organ weight, hematology, blood biochemistry, histopathology, behavior, mortality, sperm abnormality, mutagenicity, and micronucleus formation were observed and no clinical signs or adverse effects were detected. Zinc threoninate chelate had no significant teratogenic effect at a daily dose of 42 mg/kg.


1994 ◽  
Vol 13 (5) ◽  
pp. 344-360

The aromatic amine HC Blue No. 1 is a hair colorant intended exclusively for use in hair dyes. While this colorant had previously been used in concentrations up to 1.6%, current information indicates it is not presently used in any hair dyes. Animal studies indicate this ingredient is absorbed slowly through the skin. Short-term and subchronic animal toxicity studies show a dose-dependent reduction in weight gain. HC Blue No. 1 was mutagenic in some, but not all, test systems, and was associated with fetal bone malformations when given orally to pregnant rats at levels that were maternally toxic. In a National Toxicology Program feeding study, dosed male rats had a positive trend in incidence of hepatic neoplastic nodules, but not in hepatic carcinomas; dosed female rats showed a positive trend in the incidence of alveolar/bronchiolar neoplasms; and mice of both sexes showed an increase in hepatocellular carcinomas. Although it is recognized that further dermal carcinogenicity data would help clarify the different findings in the current data, such information is not expected, and it is concluded on the basis of the data that are available in this report that HC Blue No. 1 is unsafe for use in cosmetic formulations (hair dyes).


2005 ◽  
Vol 289 (4) ◽  
pp. R1131-R1136 ◽  
Author(s):  
Lori L. Woods ◽  
Julie R. Ingelfinger ◽  
Ruth Rasch

Modest maternal dietary protein restriction in the rat leads to hypertension in adult male offspring. The purpose of this study was to determine whether female rats are resistant to developing the increased blood pressure seen in male rats after maternal protein restriction. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and ANG II levels were reduced by 50–65% in male LP compared with NP pups, but were not suppressed in female LP compared with female NP. Mean arterial pressure in conscious, chronically instrumented adult female offspring (22 wk) was not different in LP (LP: 120 ± 3 mmHg vs. NP: 121 ± 2 mmHg), and glomerular filtration rate was also not different in LP vs. NP. The number of glomeruli per kidney was similar in adult LP and NP female offspring (LP: 26,050 ± 2,071 vs. NP: 26,248 ± 1,292, NP), and individual glomerular volume was also not different (LP: 0.92 ± 0.11 106μm3, LP vs. NP: 1.07 ± 0.11 106μm3); the total volume of all glomeruli per kidney was also not significantly different. Thus female rats are relatively resistant to the programming for adult hypertension by perinatal protein restriction that we have described in males. This resistance may be due to the fact that modest maternal protein restriction does not reduce the number of glomeruli with which females are endowed as it does in males. The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender.


1982 ◽  
Vol 53 (3) ◽  
pp. 703-707 ◽  
Author(s):  
K. I. Fuchs ◽  
L. G. Moore ◽  
S. Rounds

Pulmonary arterial pressure is decreased in pregnant women despite increased cardiac output, suggesting that pulmonary vascular resistance is decreased in pregnancy. To determine if pulmonary vascular reactivity is decreased in pregnant rats, lungs isolated from pregnant rats were perfused with blood from other pregnant rats at constant flow rate, and pressor responses to airway hypoxia and to angiotensin II were measured. Compared with responses obtained in lungs from nonpregnant female rats, hypoxic and angiotensin II pressor responses were blunted in pregnancy. To separate possible effects of pregnancy on the lung from those of substance(s) circulating in the blood in pregnancy, we perfused lungs from nonpregnant rats with blood from pregnant rats. Both the hypoxic and angiotensin II pressor responses were blunted by blood from pregnant rats. The angiotensin II pressor response was blunted also in lungs from pregnant rats perfused with blood from nonpregnant rats. These results suggest that a circulating substance is responsible for blunting of pulmonary vascular reactivity in pregnancy and that changes in the lung induced by pregnancy also depress angiotensin II responses. It is unlikely that estrogen and progesterone were responsible for these effects, since lungs and blood obtained from animals treated with these hormones did not have blunted pulmonary vascular reactivity.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Davood Oliaee ◽  
Mohammad Taher Boroushaki ◽  
Naiime Oliaee ◽  
Ahmad Ghorbani

To date, there is no report on safety ofArtemisia Kopetdaghensis. This study aimed to determine the possible undesirable effects ofA. Kopetdaghensison reproduction of female rats. The pregnant rats were treated (i.p.) with vehicle or 200 and 400 mg/kg ofA. Kopetdaghensishydroalcoholic extract from the 2nd to 8th day of pregnancy. Then, number and weight of neonates, duration of pregnancy, and percent of dead fetuses were determined. Also, cytotoxicity of this plant was tested using fibroblast (L929) and ovary (Cho) cell lines. TheA. Kopetdaghensishad no significant effect on duration of pregnancy, average number of neonates, and weight of neonates. However, administration of 200 and 400 mg/kg of the extract led to 30 and 44% abortion in animals, respectively. The extract at concentrations ≥200 μg/mL significantly (P<0.001) inhibited the proliferation of L929 fibroblast cells. Regarding the Cho cells, the extract induced toxicity only at concentration of 800 μg/mL (P<0.01). Our results showed that continuous consumption ofA. Kopetdaghensisin pregnancy may increase the risk of abortion and also may have toxic effect on some cells.


2016 ◽  
Vol 3 (4) ◽  
pp. 563-567
Author(s):  
Семенова ◽  
M. Semenova ◽  
Ковешникова ◽  
E. Koveshnikova

Objective of research: To estimate the effect of new combination drugs Aversect Forte and Aversect Combi on rats. Materials and methods: The present experiment for the evaluation of eventual embyotoxic and teratogenic properties of drugs Aversect Forte and Aversect Combi was conducted on 32 female and 8 male rats based on the current methodological guidelines. Pregnant female rats were divided into 2 experimental and 2 control groups. Drugs were applied between the 7th and the 14th day of pregnancy taking into account the highest sensitivity of embryos towards different types of influence within this time period. Aversect Forte and Aversect Combi were injected to pregnant rats subcutaneously at a dose of 0,3 mg a.i./kg of individual body weight. Rats from the control group received a forming mixture in comparable volume. Within the whole period of pregnancy, we observed the general clinical condition of female rats. Results and discussion: Effects of new domestic preparations Aversect Forte and Aversect Combi on the antenatal development of the rat via subcutaneous injection of preparations to female rats at a dose of 0,3 mg a.i./kg between the 7th and the 14th day of pregnancy were estimated. The test preparations did not cause any external and internal developmental anomalies; indicators of embryo death, mass and dimensions of embryos were at the actual level of control and physiological parameters for that type of animals.


Author(s):  
Rima Benatoui ◽  
Abdelmadjid Bairi ◽  
Abdelkrim Tahraoui

Objective: During the last decade, the role of the β-carboline alkaloid harmine has essentially been studied with regard to its anxiolytic effect, as it was done in our laboratory; therefore, this study has been progressed to cover the effect of this alkaloid on pregnant wistar rats.Methods: The molecule was used at doses of 10 mg/kg, 15 mg/kg, pregnant female rats were divided into three groups according to the stage of pregnancy: first, second, and the third week of pregnancy. Each group has been subdivided into seven subgroups: control group, two treated groups with harmine, acute footshock stress at 1,2mA, sub-acute footshock stress at 0,4mA, psychological stress, and the treated group that footshocked after with 1,2mA, all groups were carried out open field test, plus maze test and light/dark box test.Results: Thigmotaxis is reflected by the significant increase in the traveled distance in peripheral area in the open field of the three groups ‘weeks’ at dose of 10 mg/kg, the enhancement in the number and time of rearing, at both doses, during the second and the last week, the significant increase in the number of entries ‘in open arms’ in plus-maze during the first and third weeks at 15 mg/kg, and the significant decreased in time spent in the light compartment of the light/dark box at the same dose of all groups ‘weeks’ were noticed, which confirm the anxiolytic effect of the alkaloid, even in the case of the footschock stressed pregnant rats of all groups ‘weeks’ that enhancement of number of enties into open arms during the plus maze test.Conclusion: So we can conclude that the anxiolytic effect of harmine not shortening to male rats, but expands to female pregnant wistar rats, and establishes its effect by diminishing time in light compartment of light/dark box and number of entries in open arms of plus maze, in other hand, the increase in the number and the time of rearing reflects the enhancement of exploratory behavior.


2000 ◽  
Vol 279 (4) ◽  
pp. R1298-R1304 ◽  
Author(s):  
Lee A. Danielson ◽  
Laurie J. Kercher ◽  
Kirk P. Conrad

Chronic administration of the hormone relaxin elicits renal vasodilation that is dependent on nitric oxide (NO) in both conscious intact and ovariectomized female rats. Our first objective was to test whether the hormone, when administered to approximate serum concentrations found in midterm pregnant rats, induces renal vasodilation in males. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased significantly, on average, by 33 and 49% over baseline, respectively, after 5 days of recombinant human relaxin (rhRLX) administration to 12 conscious male rats by subcutaneous osmotic minipump. There were also significant decreases in hematocrit, plasma osmolality, and sodium concentration. Another objective was to determine whether endogenous endothelin (ET; via the endothelial ETB receptor) mediates the NO-dependent renal vasodilation produced by relaxin. rhRLX or vehicle was administered to conscious female rats ( n = 9 and 8 rats, respectively). On the fifth day, baseline GFR and ERPF were both increased, on average, by 20–30% in the rats administered rhRLX ( P < 0.05 vs. vehicle). Next, the specific ETB-receptor antagonist RES-701-1 was infused intravenously over 4 h in both groups of rats. In response to RES-701-1, there was a significant decline in both GFR and ERPF in the rats receiving rhRLX such that renal function converged in the two groups of animals. We conclude 1) relaxin induces marked changes in the renal circulation and in osmoregulation regardless of gender and 2) relaxin-induced renal vasodilation and hyperfiltration are mediated by endothelin through the endothelial ETB receptor subtype and NO.


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