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Author Youket, R.J.; Carnevale, J.M.; Houpt, K.A.; Houpt, T.R.
Title Humoral, hormonal and behavioral correlates of feeding in ponies: the effects of meal frequency Type Journal Article
Year (up) 1985 Publication Journal of animal science Abbreviated Journal J. Anim Sci.
Volume 61 Issue 5 Pages 1103-1110
Keywords Animals; Behavior, Animal/physiology; Blood Glucose/*analysis; Blood Proteins/*analysis; Blood Volume; *Eating; Feeding Behavior/physiology; Female; Heart Rate; Horses/blood/*physiology; Male; Osmolar Concentration; Osmotic Pressure; Triiodothyronine/*blood
Abstract The effect of meal frequency on body fluid, glucose, triiodothyronine (T3), heart rate and behavior was measured in 10 ponies. A simple reversal design was used in which each pony received one meal/day (1X) for 2 wk and six meals/day (6X) for 2 wk. The total intake/day was held constant. Feeding was followed by a rise in plasma levels of glucose, T3, protein and osmolality. One large meal was followed by significantly greater changes in all of the variables than was a meal one-sixth the size. Plasma T3 rose from 41 +/- 5 (SE) ng/liter before feeding to 43 +/- 5 ng/liter following a small meal, but rose significantly higher, from 39 +/- 4 to 60 +/- 10 ng/liter, following a large meal. Glucose rose from 84 +/- 3 to 109 +/- 7 mg/dl following a small meal and rose significantly higher, from 83 +/- 3 to 154 +/- 11 mg/dl, after a large meal. Plasma protein rose from 6.55 +/- .14 to 6.62 +/- .16 g/dl following a small meal and from 6.45 +/- .14 to 6.99 +/- .11 g/dl following a large meal. Osmolality rose from 227 +/- 1 mosmol/liter before to 279 +/- 1 mosmol/liter following a small meal and significantly higher from 278 +/- 2 to 285 +/- 1 mosnol/liter following a large meal. Heart rate rose from 42 beats/min in the absence of feed to 50 beats/min when food was visible to the ponies and did not rise higher when eating began. There were no significant differences in the cardiac response to one large meal and that to a small meal.(ABSTRACT TRUNCATED AT 250 WORDS)
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-8812 ISBN Medium
Area Expedition Conference
Notes PMID:4077755 Approved no
Call Number refbase @ user @ Serial 51
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Author Sufit, E.; Houpt, K.A.; Sweeting, M.
Title Physiological stimuli of thirst and drinking patterns in ponies Type Journal Article
Year (up) 1985 Publication Equine veterinary journal Abbreviated Journal Equine Vet J
Volume 17 Issue 1 Pages 12-16
Keywords Animals; Blood Proteins/analysis; Drinking Behavior/drug effects/*physiology; Furosemide/pharmacology; Horses/*physiology; Male; Osmolar Concentration; Osmotic Pressure; Sodium Chloride/pharmacology; Thirst/drug effects/*physiology; Time Factors; Water Deprivation/physiology
Abstract The stimuli that elicit thirst were studied in four ponies. Nineteen hours of water deprivation produced an increase in plasma protein from 67 +/- 0.1 g/litre to 72 +/- 2 g/litre, a mean (+/- se) increase in plasma sodium from 139 +/- 3 to 145 +/- 2 mmol/litre and an increase in plasma osmolality from 297 +/- 1 to 306 +/- 2 mosmol/litre. Undeprived ponies drank 1.5 +/- 0.9 kg/30 mins; 19 h deprived ponies drank 10.2 +/- 2.5 kg/30 mins and corrected the deficits in plasma protein, plasma sodium and plasma osmolality as well as compensating for the water they would have drunk during the deprivation period. In order to determine if an increase in plasma osmolality would stimulate thirst, 250 ml of 15 per cent sodium chloride was infused intravenously. The ponies drank when osmolality increased 3 per cent and when plasma sodium rose from 136 +/- 3 mmol/litre to 143 +/- 3 mmol/litre. Ponies infused with 15 per cent sodium chloride drank 2.9 +/- 0.7 kg; those infused with 0.9 per cent sodium chloride drank 0.7 +/- 0.5 kg. In order to determine if a decrease in plasma volume would stimulate thirst, ponies were injected with 1 or 2 mg/kg bodyweight (bwt) frusemide. Plasma protein rose from 68 +/- 2 g/litre pre-injection to 75 +/- 2 g/litre 1 h after 1 mg/kg bwt frusemide and to 81 +/- 1 g/litre 1 h after 2 mg/kg bwt frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0425-1644 ISBN Medium
Area Expedition Conference
Notes PMID:3979367 Approved no
Call Number refbase @ user @ Serial 56
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Author Trim, C.M.; Moore, J.N.; Clark, E.S.
Title Renal effects of dopamine infusion in conscious horses Type Journal Article
Year (up) 1989 Publication Equine veterinary journal. Supplement Abbreviated Journal Equine Vet J Suppl
Volume Issue 7 Pages 124-128
Keywords Animals; Blood Pressure/drug effects/physiology; Consciousness/*physiology; Creatinine/blood; Dopamine/administration & dosage/*pharmacology; Dose-Response Relationship, Drug; Female; Heart Rate/drug effects/physiology; Horses/*physiology; Infusions, Intravenous/veterinary; Kidney/blood supply/*drug effects/physiology; Osmolar Concentration; Potassium/blood; Random Allocation; Regional Blood Flow/drug effects/physiology; Renal Artery/drug effects/physiology/ultrasonography; Sodium/blood; Time Factors; Ultrasonography/methods/veterinary; Urination/physiology
Abstract An ultrasonic flow probe was implanted around a branch of the left renal artery in five horses. The effects of dopamine were studied in the unsedated horses 10 days after surgery. Three experiments, separated by at least two days, were performed in random order on each horse. In two experiments, dopamine was infused intravenously for 60 mins at either 2.5 and 5.0 micrograms/kg bodyweight (bwt)/min. Saline was infused for 60 mins before and after each infusion, and for 180 mins in the third experiment as a control. Renal blood flow increased during administration of dopamine at both dose rates (P = 0.0001). Urine volume increased (P = 0.055), and osmolality decreased (P < 0.05), with infusion of dopamine at 5.0 micrograms/kg bwt/min. Arterial blood pressure and heart rate were not significantly affected. Fractional excretions of sodium and potassium were not significantly changed with dopamine infusion. The higher dopamine dose rate was accompanied by dysrhythmias in some horses.
Address Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN ISBN Medium
Area Expedition Conference
Notes PMID:9118094 Approved no
Call Number refbase @ user @ Serial 99
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Author Colahan, P.; Lindsey, E.; Nunier, C.
Title Determination of the center of pressure of the hoofs of the forelimbs of horses standing on a flat level surface Type Journal Article
Year (up) 1993 Publication Acta Anatomica Abbreviated Journal Acta Anat (Basel)
Volume 146 Issue 2-3 Pages 175-178
Keywords Animals; Forelimb/*physiology; Hoof and Claw/*physiology; Horses/*physiology; *Posture; Pressure
Abstract The pressure exerted on a flat level surface by recently trimmed, unshod hoofs of the front limbs of 23 sound, adult horses was measured using pressure-sensitive film and a specially built cassette. The horses were tranquilized and stood with one foot on the 2.9-cm-thick cassette and the other on a block of equal height. The hoofs were observed for motion during the measurement, and the developed film was examined for improper alignment of the film or slipping of the hoof. The center of pressure was located using the method of weighted proportions of Barrey. This static measurement system with a long measurement time and the number of measurements reduced the influence of variables inherent in the horses' behavior and the measuring system. The calculated point was recorded as falling medial to, lateral to or on a line bisecting the central sulcus of the frog. In the dorsal to palmar orientation the point was classified with reference to a line drawn halfway between the most dorsal and the most palmar mark on the film. Forty-six percent of the calculated centers of pressure were located in the medial heel area. Binomial analysis for large samples indicates that this was a significant variation from a random distribution. Seventy-six percent of the centers were located in or on the borders of the medial heel.
Address College of Veterinary Medicine, University of Florida, Gainesville 32608-0136
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0001-5180 ISBN Medium
Area Expedition Conference
Notes PMID:8470462 Approved no
Call Number refbase @ user @ Serial 1946
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Author Grubb, T.L.; Foreman, J.H.; Benson, G.J.; Thurmon, J.C.; Tranquilli, W.J.; Constable, P.D.; Olson, W.O.; Davis, L.E.
Title Hemodynamic effects of calcium gluconate administered to conscious horses Type Journal Article
Year (up) 1996 Publication Journal of veterinary internal medicine / American College of Veterinary Internal Medicine Abbreviated Journal J Vet Intern Med
Volume 10 Issue 6 Pages 401-404
Keywords Animals; Blood Pressure/drug effects/physiology; Calcium/blood; Calcium Gluconate/administration & dosage/*pharmacology; Cardiac Output/drug effects/physiology; Consciousness/*physiology; Dose-Response Relationship, Drug; Female; Heart Rate/drug effects/physiology; Hemodynamic Processes/*drug effects/physiology; Horses/blood/*physiology; Infusions, Intravenous; Male; Myocardial Contraction/drug effects/physiology; Respiration/drug effects/physiology; Stroke Volume/drug effects/physiology; Time Factors
Abstract Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.
Address Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0891-6640 ISBN Medium
Area Expedition Conference
Notes PMID:8947873 Approved no
Call Number refbase @ user @ Serial 97
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Author Carroll, G.L.; Matthews, N.S.; Hartsfield, S.M.; Slater, M.R.; Champney, T.H.; Erickson, S.W.
Title The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies Type Journal Article
Year (up) 1997 Publication Veterinary surgery : VS : the official journal of the American College of Veterinary Surgeons Abbreviated Journal Vet Surg
Volume 26 Issue 1 Pages 69-77
Keywords Adrenergic alpha-Antagonists/administration & dosage/*pharmacology; Animals; Behavior, Animal/drug effects/physiology; Blood Glucose/metabolism; Blood Pressure/drug effects/physiology; Consciousness/physiology; Dose-Response Relationship, Drug; Drug Interactions; Epinephrine/blood; Fatty Acids, Nonesterified/blood; Female; Heart Rate/drug effects/physiology; Horse Diseases/metabolism/physiopathology/psychology; Horses/blood/metabolism/*physiology; Hydrocortisone/blood; Hypnotics and Sedatives/administration & dosage/*pharmacology; Imidazoles/administration & dosage/*pharmacology; Injections, Intravenous; Male; Norepinephrine/blood; Receptors, Adrenergic, alpha/drug effects/*physiology; Stress/metabolism/physiopathology/veterinary; Time Factors; Tolazoline/administration & dosage/*pharmacology
Abstract Six ponies were used to investigate the effect of tolazoline antagonism of detomidine on physiological responses, behavior, epinephrine, norepinephrine, cortisol, glucose, and free fatty acids in awake ponies. Each pony had a catheter inserted into a jugular vein 1 hour before beginning the study. Awake ponies were administered detomidine (0.04 mg/kg intravenously [i.v.]) followed 20 minutes later by either tolazoline (4.0 mg/kg i.v.) or saline. Blood samples were drawn from the catheter 5 minutes before detomidine administration (baseline), 5 minutes after detomidine administration, 20 minutes before detomidine administration which was immediately before the administration of tolazoline or saline (time [T] = 0), and at 5, 30, and 60 minutes after injections of tolazoline or saline (T = 5, 30, and 60 minutes, respectively). Compared with heart rate at T = 0, tolazoline antagonism increased heart rate 45% at 5 minutes. There was no difference in heart rate between treatments at 30 minutes. Blood pressure remained stable after tolazoline, while it decreased over time after saline. Compared with concentrations at T = 0, tolazoline antagonism of detomidine in awake ponies resulted in a 55% increase in cortisol at 30 minutes and a 52% increase in glucose at 5 minutes. The change in free fatty acids was different for tolazoline and saline over time. Free fatty acids decreased after detomidine administration. Free fatty acids did not change after saline administration. After tolazoline administration, free fatty acids increased transiently. Tolazoline tended to decrease sedation and analgesia at 15 and 60 minutes postantagonism. Antagonism of detomidine-induced physiological and behavioral effects with tolazoline in awake ponies that were not experiencing pain appears to precipitate a stress response as measured by cortisol, glucose, and free fatty acids. If antagonism of an alpha-agonist is contemplated, the potential effect on hormones and metabolites should be considered.
Address Department of Small Animal Medicine and Surgery, Texas A&M University, College Station, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0161-3499 ISBN Medium
Area Expedition Conference
Notes PMID:9123816 Approved no
Call Number refbase @ user @ Serial 96
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Author Natalini, C.C.; Robinson, E.P.
Title Effects of epidural opioid analgesics on heart rate, arterial blood pressure, respiratory rate, body temperature, and behavior in horses Type Journal Article
Year (up) 2003 Publication Veterinary Therapeutics : Research in Applied Veterinary Medicine Abbreviated Journal Vet Ther
Volume 4 Issue 4 Pages 364-375
Keywords 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/administration & dosage/pharmacology; Alfentanil/administration & dosage/pharmacology; Analgesics, Opioid/administration & dosage/*pharmacology; Anesthesia, Epidural/*veterinary; Animals; Behavior, Animal/drug effects; Blood Pressure/drug effects; Body Temperature/drug effects; Butorphanol/administration & dosage/pharmacology; Cross-Over Studies; Female; Heart Rate/drug effects; Horses/*physiology; Injections, Epidural/veterinary; Male; Morphine/administration & dosage/pharmacology; Respiration/drug effects; Tramadol/administration & dosage/pharmacology
Abstract Heart rate, arterial blood pressures, respiratory rate, body temperature, and central nervous system excitement were compared before and after epidural administration of morphine (0.1 mg/kg), butorphanol (0.08 mg/kg), alfentanil (0.02 mg/kg), tramadol (1.0 mg/kg), the k-opioid agonist U50488H (0.08 mg/kg), or sterile water using an incomplete Latin square crossover design in five conscious adult horses. Treatments were administered into the first intercoccygeal epidural space. Significant (P <.05) reductions in respiratory rate were detected after epidural administration of morphine, alfentanil, U50488H, and sterile water. Additionally, significant (P <.05) head ptosis was observed within the first hour after administration of morphine, U50488H, and tramadol, but neither of these changes appeared to be of clinical significance. No treatment-related changes in motor activity or behavior were observed.
Address Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1528-3593 ISBN Medium
Area Expedition Conference
Notes PMID:15136978 Approved no
Call Number Serial 1902
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Author Ganswindt, A.; Palme, R.; Heistermann, M.; Borragan, S.; Hodges, J.K.
Title Non-invasive assessment of adrenocortical function in the male African elephant (Loxodonta africana) and its relation to musth Type Journal Article
Year (up) 2003 Publication General and Comparative Endocrinology Abbreviated Journal Gen Comp Endocrinol
Volume 134 Issue 2 Pages 156-166
Keywords Adrenal Cortex/*metabolism/secretion; Adrenal Cortex Function Tests/methods/*veterinary; Adrenocorticotropic Hormone/physiology; Animals; Carbon Isotopes/diagnostic use; Chromatography, High Pressure Liquid/veterinary; Elephants/*metabolism/urine; Feces/*chemistry; Glucocorticoids/analysis/urine; Hydrocortisone/*analysis/diagnostic use/urine; Immunoenzyme Techniques/methods/veterinary; Male; Reproduction/physiology; Sexual Behavior, Animal/physiology; Stress, Psychological/diagnosis/*physiopathology; Testosterone/*analysis/diagnostic use/urine
Abstract Adult male elephants periodically show the phenomenon of musth, a condition associated with increased aggressiveness, restlessness, significant weight reduction and markedly elevated androgen levels. It has been suggested that musth-related behaviours are costly and that therefore musth may represent a form of physiological stress. In order to provide data on this largely unanswered question, the first aim of this study was to evaluate different assays for non-invasive assessment of adrenocortical function in the male African elephant by (i) characterizing the metabolism and excretion of [3H]cortisol (3H-C) and [14C]testosterone (14C-T) and (ii) using this information to evaluate the specificity of four antibodies for determination of excreted cortisol metabolites, particularly with respect to possible cross-reactions with androgen metabolites, and to assess their biological validity using an ACTH challenge test. Based on the methodology established, the second objective was to provide data on fecal cortisol metabolite concentrations in bulls during the musth and non-musth condition. 3H-C (1 mCi) and 14C-T (100 microCi) were injected simultaneously into a 16 year old male and all urine and feces collected for 30 and 86 h, respectively. The majority (82%) of cortisol metabolites was excreted into the urine, whereas testosterone metabolites were mainly (57%) excreted into the feces. Almost all radioactive metabolites recovered from urine were conjugated (86% 3H-C and 97% 14C-T). In contrast, 86% and >99% of the 3H-C and 14C-T metabolites recovered from feces consisted of unconjugated forms. HPLC separations indicated the presence of various metabolites of cortisol in both urine and feces, with cortisol being abundant in hydrolysed urine, but virtually absent in feces. Although all antibodies measured substantial amounts of immunoreactivity after HPLC separation of peak radioactive samples and detected an increase in glucocorticoid output following the ACTH challenge, only two (in feces against 3alpha,11-oxo-cortisol metabolites, measured by an 11-oxo-etiocholanolone-EIA and in urine against cortisol, measured by a cortisol-EIA) did not show substantial cross-reactivity with excreted 14C-T metabolites and could provide an acceptable degree of specificity for reliable assessment of glucocorticoid output from urine and feces. Based on these findings, concentrations of immunoreactive 3alpha,11-oxo-cortisol metabolites were determined in weekly fecal samples collected from four adult bulls over periods of 11-20 months to examine whether musth is associated with increased adrenal activity. Results showed that in each male levels of these cortisol metabolites were not elevated during periods of musth, suggesting that in the African elephant musth is generally not associated with marked elevations in glucocorticoid output. Given the complex nature of musth and the variety of factors that are likely to influence its manifestation, it is clear, however, that further studies, particularly on free-ranging animals, are needed before a possible relationship between musth and adrenal function can be resolved. This study also clearly illustrates the potential problems associated with cross-reacting metabolites of gonadal steroids in EIAs measuring glucocorticoid metabolites. This has to be taken into account when selecting assays and interpreting results of glucocorticoid metabolite analysis, not only for studies in the elephant but also in other species.
Address German Primate Centre, Department of Reproductive Biology, Kellnerweg 4, 37077 Gottingen, Germany. ganswindt@www.dpz.gdwg.de
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0016-6480 ISBN Medium
Area Expedition Conference
Notes PMID:14511986 Approved no
Call Number Equine Behaviour @ team @ Serial 4085
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Author Touma, C.; Sachser, N.; Mostl, E.; Palme, R.
Title Effects of sex and time of day on metabolism and excretion of corticosterone in urine and feces of mice Type Journal Article
Year (up) 2003 Publication General and Comparative Endocrinology Abbreviated Journal Gen Comp Endocrinol
Volume 130 Issue 3 Pages 267-278
Keywords Animals; Chromatography, High Pressure Liquid; Circadian Rhythm/*physiology; Corticosterone/*metabolism/urine; Feces/*chemistry; Female; Immunoenzyme Techniques; Kinetics; Male; Mice; Mice, Inbred C57BL; Reference Values; Sex Factors; Stress/metabolism; Time Factors; Tritium
Abstract Non-invasive techniques to monitor stress hormones in small animals like mice offer several advantages and are highly demanded in laboratory as well as in field research. Since knowledge about the species-specific metabolism and excretion of glucocorticoids is essential to develop such a technique, we conducted radiometabolism studies in mice (Mus musculus f. domesticus, strain C57BL/6J). Each mouse was injected intraperitoneally with 740 kBq of 3H-labelled corticosterone and all voided urine and fecal samples were collected for five days. In a first experiment 16 animals (eight of each sex) received the injection at 9 a.m., while eight mice (four of each sex) were injected at 9 p.m. in a second experiment. In both experiments radioactive metabolites were recovered predominantly in the feces, although males excreted significantly higher proportions via the feces (about 73%) than females (about 53%). Peak radioactivity in the urine was detected within about 2h after injection, while in the feces peak concentrations were observed later (depending on the time of injection: about 10h postinjection in experiment 1 and about 4h postinjection in experiment 2, thus proving an effect of the time of day). The number and relative abundance of fecal [3H]corticosterone metabolites was determined by high performance liquid chromatography (HPLC). The HPLC separations revealed that corticosterone was extensively metabolized mainly to more polar substances. Regarding the types of metabolites formed, significant differences were found between males and females, but not between the experiments. Additionally, the immunoreactivity of these metabolites was assessed by screening the HPLC fractions with four enzyme immunoassays (EIA). However, only a newly established EIA for 5alpha-pregnane-3beta,11beta,21-triol-20-one (measuring corticosterone metabolites with a 5alpha-3beta,11beta-diol structure) detected several peaks of radioactive metabolites with high intensity in both sexes, while the other EIAs showed only minor immunoreactivity. Thus, our study for the first time provides substantial information about metabolism and excretion of corticosterone in urine and feces of mice and is the first demonstrating a significant impact of the animals' sex and the time of day. Based on these data it should be possible to monitor adrenocortical activity non-invasively in this species by measuring fecal corticosterone metabolites with the newly developed EIA. Since mice are extensively used in research world-wide, this could open new perspectives in various fields from ecology to behavioral endocrinology.
Address Department of Behavioral Biology, Institute of Neuro and Behavioral Biology, University of Muenster, Badestrasse 9, D-48149 Muenster, Germany. touma@uni-muenster.de
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0016-6480 ISBN Medium
Area Expedition Conference
Notes PMID:12606269 Approved no
Call Number Equine Behaviour @ team @ Serial 4086
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Author Guo, G.L.; Moffit, J.S.; Nicol, C.J.; Ward, J.M.; Aleksunes, L.A.; Slitt, A.L.; Kliewer, S.A.; Manautou, J.E.; Gonzalez, F.J.
Title Enhanced acetaminophen toxicity by activation of the pregnane X receptor Type Journal Article
Year (up) 2004 Publication Toxicological sciences : an official journal of the Society of Toxicology Abbreviated Journal Toxicol Sci
Volume 82 Issue 2 Pages 374-380
Keywords Acetaminophen/pharmacokinetics/*toxicity; Analgesics, Non-Narcotic/pharmacokinetics/*toxicity; Animals; Aryl Hydrocarbon Hydroxylases/biosynthesis; Biotransformation; Blotting, Northern; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Membrane Proteins; Mice; Mice, Knockout; Oxidoreductases, N-Demethylating/biosynthesis; Pregnenolone Carbonitrile/pharmacology; Receptors, Cytoplasmic and Nuclear/*drug effects; Receptors, Steroid/*drug effects; Sulfhydryl Compounds/metabolism
Abstract The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP-induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation.
Address Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1096-6080 ISBN Medium
Area Expedition Conference
Notes PMID:15456926 Approved no
Call Number refbase @ user @ Serial 71
Permanent link to this record