TOXICITY AND METABOLIC EFFECTS OF INTRAVENOUSLY ADMINISTERED 3-NITROPROPANOL IN CATTLE

1981 ◽  
Vol 61 (3) ◽  
pp. 639-647 ◽  
Author(s):  
W. MAJAK ◽  
R. E. McDIARMID ◽  
T. UDENBERG ◽  
H. DOUWES
Keyword(s):  
Decay Rate ◽  
Gradual Increase ◽  
Decay Rates ◽  
Metabolic Effects ◽  
Bovine Blood ◽  
Respiration Rates ◽  
Plasma Nitrite ◽  
Rates Of Decay

In vitro and in vivo metabolic studies were conducted with bovine blood to determine decay rates for 3-nitropropanol (NPOH), a toxic forage constituent occurring in many Astragalus species. Methemoglobin (metHb) and plasma nitrite [Formula: see text] levels were concomitantly determined and early signs of poisoning were recorded. Subtle increases in heart and respiration rates, development of a placid, stupefied state, frothy salivation and incoordination characterized early stages of intoxication. Animals with low decay rates for NPOH showed a gradual increase in the metHb and [Formula: see text]. When the decay rate was high, a rapid increase in netHb and [Formula: see text] was observed. Acutely poisoned animals showed the highest levels of metHb and [Formula: see text] but intermediate rates of decay for NPOH. When NPOH was incubated with bovine blood in vitro, [Formula: see text] was not detected and metHb was not significantly altered, indicating that NPOH is not metabolized in bovine blood. A new method is described for determining NPOH in bovine blood.

A Sensitive Method for Assay of Mixed-Function Oxygenase (p-450 complex) in Cell Culture

1988 ◽  
Vol 15 (3) ◽  
pp. 219-223
Author(s):  
Jørgen Clausen ◽  
Søren Achim Nielsen
Keyword(s):  
Human Lymphocytes ◽  
Cellular Systems ◽  
Metabolic Effects ◽  
Assay Method ◽  
Related Family ◽  
Oxygenase Activity ◽  
Metabolic Transformation ◽  
Mixed Function Oxygenase

The mixed-function oxygenase system involved in the metabolism of drugs and xenobiotics has been extensively studied in various animal species and in various organs (1). It is now apparent that in humans the p-450 complex is one representative of a related family, expressed by 13 c-DNA genes showing approximately 36% similarity between the different subfamilies (2). In order to compare the in vivo and in vitro metabolic effects of drugs and xenobiotics, the induction capabilities of the mixed-function oxygenase must be known. The most sensitive non-isotopic assay system for determination of mixed-function oxygenase activity is the method of Nebert & Gelboin (3,4), which is based on the metabolic transformation of benzo-(a)-pyrene to its fluorescent hydroxyl derivatives (5). However, the levels of the mixed-function oxygenase enzymes in different cellular systems show great variations, with the highest activities in liver cells. Therefore, in order to use human lymphocytes and other cellular systems with low mixed-function oxygenase activities, the assay method for determining oxygenase activity must have the highest possible sensitivity. The present communication is devoted to a study aimed at increasing the sensitivity of Nebert & Gelboin's methods for assay of mixed-function oxygenase subfamilies using benzo-(a)-pyrene as a substrate.

scholarly journals Omics profiling identifies MAPK/ERK pathway as a gatekeeper of nephron progenitor metabolism

2021 ◽  
Author(s):  
Hyuk Nam Kwon ◽  
Kristen Kurtzeborn ◽  
Xing Jin ◽  
Bruno Reversade ◽  
Sunghyouk Park ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Mitogen Activated Protein Kinase ◽  
Metabolic Effects ◽  
Erk Pathway ◽  
Double Knockout ◽  
Nephron Progenitor ◽  
Progenitor Maintenance

Nephron endowment is defined by fetal kidney growth and it critically dictates renal health in adults. Despite the advances in understanding the molecular regulation of nephron progenitor maintenance, propagation, and differentiation, the causes for low congenital nephron count and contribution of basic metabolism to nephron progenitor regulation remain poorly studied. Here we have analyzed the metabolic effects that depend on and are triggered by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, which is an essential intracellular cascade required for nephron progenitor maintenance. Our combined approach utilizing LC/MS-based metabolomics and transcriptional profiling of MAPK/ERK-deficient cells identified 18 out of total 46 metabolites (38 untargeted and 8 targeted) that were down-regulated. These represent glycolysis, gluconeogenesis, pentose phosphate, glycine, and proline pathways among others. We focused our functional characterization of identified metabolites on pyruvate and proline. Use of in vitro kidney cultures revealed dosage-specific functions for pyruvate in not only controlling ureteric bud branching but also determining progenitor and differentiated (tip-trunk) cell identities. Our in vivo characterization of Pycr1/2 double knockout kidneys revealed functional requirement for proline metabolism in nephron progenitor maintenance. In summary, our results demonstrate that MAPK/ERK cascade regulates energy and amino acid metabolism in developing kidney where these metabolic pathways specifically regulate progenitor preservation.

Nitric Oxide Mediates Hepatic Cytochrome P450 Dysfunction Induced by Endotoxin

1996 ◽  
Vol 84 (6) ◽  
pp. 1435-1442 ◽  
Author(s):  
Claudia M. Muller ◽  
Annette Scierka ◽  
Richard L. Stiller ◽  
Yong-Myeong Kim ◽  
Ryan D. Cook ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Sprague Dawley ◽  
Cytochrome P450 Content ◽  
Nitrate Concentrations ◽  
Hypnotic Drugs ◽  
Plasma Nitrite

Background Animals subjected to immunostimulatory conditions (sepsis) exhibit decreased total cytochrome P450 content and decreased P450-dependent drug metabolism. Cytochrome P450 function is of clinical significance because it mediates the metabolism of some opioid and hypnotic drugs. The authors tested the hypothesis that reduced P450 function and decreased drug metabolism in sepsis are mediated by endotoxin-enhanced synthesis of nitric oxide. Methods Hepatic microsomes were prepared from male Sprague-Dawley rats in nontreated rats, rats pretreated with phenobarbital and rats receiving aminoguanidine or NG-L-monomethyl-arginine alone. Nitric oxide synthesis was augmented for 12 h with a single injection of bacterial lipopolysaccharides. Nitric oxide synthase was inhibited with aminoguanidine or N(G)-L-monomethyl-arginine during the 12 h of endotoxemia in some animals. Plasma nitrite and nitrate concentrations were measured in vivo, and total microsomal P450 content, and metabolism of ethylmorphine and midazolam in vitro. Results Administration of endotoxin increased plasma nitrite and nitrate concentrations, decreased total cytochrome P450 content, and decreased metabolism of ethylmorphine and midazolam. Inhibition of nitric oxide formation by aminoguanidine or N(G)-L-monomethyl-arginine partially prevented the endotoxin-induced effects in the nontreated and phenobarbital-treated groups. Aminoguanidine or N(G)-L-monomethyl-arginine alone did not have an effect on either total cytochrome P450 content or P450-dependent drug metabolism. Plasma nitrite and nitrate concentrations correlated significantly negatively with P450 content (nontreated r = -0.88, phenobarbital r = -0.91), concentrations of formed formaldehyde (nontreated r = -0.87, phenobarbital r = -0.95), and concentrations of midazolam metabolites (4-OH midazolam nontreated r = -0.88, phenobarbital r = -0.93, and 1'-OH midazolam nontreated r = -0.88, phenobarbital r = -0.97). Conclusions Altered hepatic microsomal ethylmorphine and midazolam metabolism during sepsis is mediated in large part by nitric oxide.

scholarly journals Developmental aspects of adipose tissue in GH receptor and prolactin receptor gene disrupted mice: site-specific effects upon proliferation, differentiation and hormone sensitivity

2006 ◽  
Vol 191 (1) ◽  
pp. 101-111 ◽  
Author(s):  
David J Flint ◽  
Nadine Binart ◽  
Stephanie Boumard ◽  
John J Kopchick ◽  
Paul Kelly
Keyword(s):  
Adipose Tissue ◽  
Receptor Gene ◽  
Metabolic Effects ◽  
Wild Type ◽  
Extrinsic Factors ◽  
Differentiation Potential ◽  
Site Specific ◽  
Proliferation And Differentiation

Direct metabolic effects of GH on adipose tissue are well established, but effects of prolactin (PRL) have been more controversial. Recent studies have demonstrated PRL receptors on adipocytes and effects of PRL on adipose tissue in vitro. The role of GH in adipocyte proliferation and differentiation is also controversial, since GH stimulates adipocyte differentiation in cell lines, whereas it stimulates proliferation but inhibits differentiation of adipocytes in primary cell culture. Using female gene disrupted (ko) mice, we showed that absence of PRL receptors (PRLRko) impaired development of both internal and s.c. adipose tissue, due to reduced numbers of adipocytes, an effect differing from that of reduced food intake, where cell volume is decreased. In contrast, GHRko mice exhibited major decreases in the number of internal adipocytes, whereas s.c. adipocyte numbers were increased, even though body weight was decreased by 40–50%. The changes in adipose tissue in PRLRko mice appeared to be entirely due to extrinsic factors since preadipocytes proliferated and differentiated in similar fashion to wild-type animals in vitro and their response to insulin and isoproterenol was similar to wild-type animals. This contrasted with GHRko mice, where s.c. adipocytes proliferated, differentiated, and responded to hormones in identical fashion to controls, whereas parametrial adipocytes exhibited markedly depressed proliferation and differentiation potential and failed to respond to insulin or noradrenaline. Our results provide in vivo evidence that both GH and PRL stimulate differentiation of adipocytes but that the effects of GH are site specific and induce intrinsic changes in the precursor population, which are retained in vitro.

Azoxystrobin, a mitochondrial complex III Qo site inhibitor, exerts beneficial metabolic effects in vivo and in vitro

2014 ◽  
Vol 1840 (7) ◽  
pp. 2212-2221 ◽  
Author(s):  
An-Hui Gao ◽  
Yan-Yun Fu ◽  
Kun-Zhi Zhang ◽  
Mei Zhang ◽  
Hao-Wen Jiang ◽  
...  
Keyword(s):  
Complex Iii ◽  
Metabolic Effects ◽  
Mitochondrial Complex ◽  
Qo Site

scholarly journals Metabolic effects of the major component of bovine growth hormone

1971 ◽  
Vol 122 (5) ◽  
pp. 633-640 ◽  
Author(s):  
N. I. Swislocki ◽  
M. Sonenberg ◽  
M. Kikutani
Keyword(s):  
Growth Hormone ◽  
Deae Cellulose ◽  
Heterogeneous Material ◽  
Parent Material ◽  
Metabolic Effects ◽  
Sedimentation Equilibrium ◽  
Bovine Growth Hormone ◽  
Hormone Effects

Bovine growth hormone, subjected to DEAE-cellulose chromatography, yielded one major and several minor components. The various chromatographic fractions of bovine growth hormone were compared with the parent material for their ability to promote hormone effects in vivo and in vitro. The major component of bovine growth hormone was homogeneous by acrylamide-gel electrophoresis, rechromatography and sedimentation equilibrium. Its amino acid composition was similar to that of the parent hormone. The major component possessed all the qualitative activities present in the original heterogeneous material, including promotion of acute hypoglycaemia and hypolipaemia. In studies in vitro in adipose-tissue segments the major component of the hormone increased entry of glucose and its oxidation to CO2, conversion of glucose into glyceride glycerol, release of glycerol and incorporation of histidine into adiposetissue protein. Other chromatographic fractions of bovine growth hormone were not homogeneous and possessed some but not all of the metabolic activities attributed to the hormone preparations or its major component. Thus, the metabolic effects obtained with bovine growth-hormone preparations in vivo and in vitro can be obtained with the major homogeneous component of the hormone. This observation precludes the possibility that the metabolic effects obtained with bovine growth-hormone preparations are due to the combined actions of a number of components found therein.

Metabolic effects of vanadyl sulfate in humans with non—insulin-dependent diabetes mellitus: In vivo and in vitro studies

Metabolism ◽  
2000 ◽  
Vol 49 (3) ◽  
pp. 400-410 ◽  
Author(s):  
Allison B. Goldfine ◽  
Mary-Elizabeth Patti ◽  
Lubna Zuberi ◽  
Barry J. Goldstein ◽  
Raeann LeBlanc ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
In Vitro Studies ◽  
Insulin Dependent Diabetes ◽  
Vanadyl Sulfate ◽  
Metabolic Effects ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

Chara braunii (Charales, Charophyta) in an Arid Rainfed Waterbody, Saudi Arabia

1999 ◽  
Vol 47 (3) ◽  
pp. 427 ◽  
Author(s):  
M. I. Hussain ◽  
T. M. Khoja
Keyword(s):  
Saudi Arabia ◽  
Aquatic Vegetation ◽  
Gradual Increase ◽  
Water Level Fluctuations ◽  
Salinity Range ◽  
Concentration Of Ions ◽  
Temporal Succession ◽  
Vegetation Water

An account is given of a typical rainfed waterbody in the Al-Ammariyah Wadi (Saudi Arabia), with special reference to charophyte vegetation, water chemistry and topography of the area, which was studied from April 1996 to July 1997. Recurring patterns following rainfall and inundation of the waterbody are described as a model of temporal succession of biotic communities. Unispecific Chara braunii Gm. meadows were the first aquatic vegetation to emerge and overwhelmingly dominated the freshwater lentic ecosystem. This was followed by plankton and desert plants as the waterbody dried out. Chara braunii is reported as a new record for the Saudi Arabian charoflora. The species is characterised as stenohaline and tends to grow in vivo and in vitro in the salinity range of 0.2–0.8‰. A gradual increase in elements and ions (Si 20–31 mg L–1 and pH 6.8–7.6) in the water was demonstrated as the waterbody desiccated. As a result of the increasing concentration of ions and pH, C. braunii developed heavy encrustation, and hastened fructification prior to desiccation of the waterbody between June and July 1997. Survival and emergence of C. braunii is positively correlated with drought resistant-oospores, specificity to hyposalinity, water-level fluctuations, and absence of herbivores.

In vitro and in vivo kinetic handling of nitrite in blood: effects of varying hemoglobin oxygen saturation

2007 ◽  
Vol 293 (3) ◽  
pp. H1508-H1517 ◽  
Author(s):  
Arlin B. Blood ◽  
Gordon G. Power
Keyword(s):  
Nitric Oxide ◽  
Time Course ◽  
Kinetic Properties ◽  
Hemoglobin Oxygen Saturation ◽  
Hypoxic Conditions ◽  
Oxygenation Condition ◽  
Plasma Nitrite ◽  
Kinetics Of

Growing evidence suggests that nitrite, acting via reduction to nitric oxide by deoxyhemoglobin, may play an important role in local control of blood flow during hypoxia. To investigate the effect of hypoxia (65 Torr arterial Po2) on the kinetic properties of nitrite, a bolus injection of sodium nitrite (10 mg/kg iv) was given to normoxic or hypoxic newborn lambs, and the time course of plasma nitrite and methemoglobin (MetHb) concentrations was measured. The in vivo kinetics of nitrite disappearance from plasma were biphasic and were not affected by hypoxia. Changes in MetHb, a product of the nitrite-hemoglobin reaction, also did not differ with the level of oxygenation. Hypoxia potentiated the hypotensive effects of nitrite on pulmonary and systemic arterial pressures. The disappearance of nitrite from plasma was equivalent to the increase in MetHb on a molar basis. In contrast, nitrite metabolism in sheep blood in vitro resulted in more than one MetHb per nitrite equivalent under mid- and high-oxygenation conditions: oxyhemoglobin (HbO2) saturation = 50.3 ± 1.7% and 97.0 ± 1.3%, respectively. Under the low-oxygenation condition (HbO2 saturation = 5.2 ± 0.9%), significantly less than 1 mol of MetHb was produced per nitrite equivalent, indicating that a significant portion of nitrite is metabolized through pathways that do not produce MetHb. These data support the idea that the vasodilating effects of nitrite are potentiated under hypoxic conditions due to the reduction of nitrite to nitric oxide by deoxyhemoglobin.

scholarly journals 5α-Reduced glucocorticoids: a story of natural selection

2011 ◽  
Vol 212 (2) ◽  
pp. 111-127 ◽  
Author(s):  
Mark Nixon ◽  
Rita Upreti ◽  
Ruth Andrew
Keyword(s):  
Metabolic Disease ◽  
Prostatic Hyperplasia ◽  
Metabolic Effects ◽  
Reductase Inhibitors ◽  
Inflammatory Status ◽  
Increased Activity ◽  
Inflammatory Insult

5α-Reduced glucocorticoids (GCs) are formed when one of the two isozymes of 5α-reductase reduces the Δ4–5double bond in the A-ring of GCs. These steroids are largely viewed inert, despite the acceptance that other 5α-dihydro steroids, e.g. 5α-dihydrotestosterone, retain or have increased activity at their cognate receptors. However, recent findings suggest that 5α-reduced metabolites of corticosterone have dissociated actions on GC receptors (GRs)in vivoandin vitroand are thus potential candidates for safer anti-inflammatory steroids. 5α-Dihydro- and 5α-tetrahydro-corticosterone can bind with GRs, but interest in these compounds had been limited, since they only weakly activated metabolic gene transcription. However, a greater understanding of the signalling mechanisms has revealed that transactivation represents only one mode of signalling via the GR and recently the abilities of 5α-reduced GCs to suppress inflammation have been demonstratedin vitroandin vivo. Thus, the balance of parent GC and its 5α-reduced metabolite may critically affect the profile of GR signalling. 5α-Reduction of GCs is up-regulated in liver in metabolic disease and may represent a pathway that protects from both GC-induced fuel dyshomeostasis and concomitant inflammatory insult. Therefore, 5α-reduced steroids provide hope for drug development, but may also act as biomarkers of the inflammatory status of the liver in metabolic disease. With these proposals in mind, careful attention must be paid to the possible adverse metabolic effects of 5α-reductase inhibitors, drugs that are commonly administered long term for the treatment of benign prostatic hyperplasia.

Sign in / Sign up

Export Citation Format

Share Document