Records |
Author |
Gavrilova, O.; Haluzik, M.; Matsusue, K.; Cutson, J.J.; Johnson, L.; Dietz, K.R.; Nicol, C.J.; Vinson, C.; Gonzalez, F.J.; Reitman, M.L. |
Title |
Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass |
Type |
Journal Article |
Year |
2003 |
Publication |
The Journal of biological chemistry |
Abbreviated Journal |
J Biol Chem |
Volume |
278 |
Issue |
36 |
Pages |
34268-34276 |
Keywords |
Adipose Tissue/*metabolism; Animals; Blotting, Southern; Blotting, Western; Female; Hypoglycemia/genetics; Insulin Resistance/genetics; Lipid Metabolism; Liver/*metabolism; Liver Diseases/genetics/*metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; RNA/metabolism; Receptors, Cytoplasmic and Nuclear/*genetics/*physiology; Recombination, Genetic; Thiazoles/pharmacology; *Thiazolidinediones; Time Factors; Transcription Factors/*genetics/*physiology; Triglycerides/*metabolism |
Abstract |
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that mediates the antidiabetic effects of thiazolidinediones. PPAR gamma is present in adipose tissue and becomes elevated in fatty livers, but the roles of specific tissues in thiazolidinedione actions are unclear. We studied the function of liver PPAR gamma in both lipoatrophic A-ZIP/F-1 (AZIP) and wild type mice. In AZIP mice, ablation of liver PPAR gamma reduced the hepatic steatosis but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin resistance. Inactivation of AZIP liver PPAR gamma also abolished the hypoglycemic and hypolipidemic effects of rosiglitazone, demonstrating that, in the absence of adipose tissue, the liver is a primary and major site of thiazolidinedione action. In contrast, rosiglitazone remained effective in non-lipoatrophic mice lacking liver PPAR gamma, suggesting that adipose tissue is the major site of thiazolidinedione action in typical mice with adipose tissue. Interestingly, mice without liver PPAR gamma, but with adipose tissue, developed relative fat intolerance, increased adiposity, hyperlipidemia, and insulin resistance. Thus, liver PPAR gamma regulates triglyceride homeostasis, contributing to hepatic steatosis, but protecting other tissues from triglyceride accumulation and insulin resistance. |
Address |
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. oksanag@bdg10.niddk.nih.gov |
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ISSN |
0021-9258 |
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PMID:12805374 |
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no |
Call Number |
refbase @ user @ |
Serial |
81 |
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Author |
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. |
Title |
PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis |
Type |
Journal Article |
Year |
2004 |
Publication |
Carcinogenesis |
Abbreviated Journal |
Carcinogenesis |
Volume |
25 |
Issue |
9 |
Pages |
1747-1755 |
Keywords |
9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers |
Abstract |
Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis. |
Address |
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
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0143-3334 |
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PMID:15073042 |
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no |
Call Number |
refbase @ user @ |
Serial |
76 |
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Author |
Harman, F.S.; Nicol, C.J.; Marin, H.E.; Ward, J.M.; Gonzalez, F.J.; Peters, J.M. |
Title |
Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis |
Type |
Journal Article |
Year |
2004 |
Publication |
Nature medicine |
Abbreviated Journal |
Nat Med |
Volume |
10 |
Issue |
5 |
Pages |
481-483 |
Keywords |
Animals; Azoxymethane/toxicity; Colonic Neoplasms/etiology/genetics/*prevention & control; Colonic Polyps/etiology/genetics/pathology/prevention & control; Disease Models, Animal; Mice; Mice, Knockout; Mice, Mutant Strains; Phenotype; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*physiology; Transcription Factors/deficiency/genetics/*physiology |
Abstract |
Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemically induced mouse models, colon polyp formation was significantly greater in mice nullizygous for PPAR-delta. In contrast to previous reports suggesting that activation of PPAR-delta potentiates colon polyp formation, here we show that PPAR-delta attenuates colon carcinogenesis. |
Address |
Department of Veterinary Science and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. jmp21@psu.edu |
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1078-8956 |
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PMID:15048110 |
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no |
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refbase @ user @ |
Serial |
77 |
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Author |
Nicol, C.J. |
Title |
The social transmission of information and behaviour |
Type |
Journal Article |
Year |
1995 |
Publication |
Applied Animal Behaviour Science |
Abbreviated Journal |
Appl. Anim. Behav. Sci. |
Volume |
44 |
Issue |
2-4 |
Pages |
79-98 |
Keywords |
Social learning; Imitation; Social facilitation; Cultural transmission; Stereotypies |
Abstract |
Social influences on established behaviour and on the acquisition of new information and behaviour are reviewed. Distinctions between social facilitation and contagious behaviour are drawn and suggestions for further research on contagious behaviour are made. Socially derived visual, olfactory and auditory cues are considered as important influences on behaviour and subsequent learning. The evidence supporting two potential mechanisms of social learning, i.e. stimulus enhancement followed by individual learning, and imitation, is reviewed in detail. It is argued that the functions of social learning are similarly heterogeneous and include motor skill acquisition, gathering of environmental information, and social conformity. Factors affecting the spread of socially acquired skills, including the social relationship between demonstrator and observer, are highlighted. Lastly, the few studies of social learning that have been conducted with domestic species are reviewed and potential applied goals that could stimulate further research in this area are suggested. |
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no |
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refbase @ user @ |
Serial |
577 |
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Author |
Waters, A.J.; Nicol, C.J.; French, N.P. |
Title |
Factors influencing the development of stereotypic and redirected behaviours in young horses: findings of a four year prospective epidemiological study |
Type |
Journal Article |
Year |
2002 |
Publication |
Equine veterinary journal |
Abbreviated Journal |
Equine Vet J |
Volume |
34 |
Issue |
6 |
Pages |
572-579 |
Keywords |
Age Factors; Animal Husbandry/*methods; Animal Welfare; Animals; *Behavior, Animal; Female; Horse Diseases/epidemiology/prevention & control/*psychology; Horses; Housing, Animal; Longitudinal Studies; Male; Prevalence; Prospective Studies; Risk Factors; *Stereotyped Behavior; Weaning |
Abstract |
Stereotypies are invariant and repetitive behaviour patterns that seemingly have no function, which tend to develop in captive animals faced with insoluble problems and may be indicative of reduced welfare. A 4 year prospective study of the factors influencing the development of stereotypic and redirected behaviours (abnormal behaviour) in a population of 225 young Thoroughbred and part-Thoroughbred horses was conducted between 1995 and 1999. Abnormal behaviour affected 34.7% of the population. Multivariable analysis showed that foals of low- or middle-ranking mares were less likely to develop abnormal behaviour than foals of dominant mares (rate ratio (RR) 0.23, P<0.01; RR 0.48, P<0.01, respectively). Weaning by confinement in a stable or barn was associated with an increased rate of development of abnormal behaviour, compared with paddock-weaning (RR 2.19, P<0.05), and housing in barns, rather than at grass after weaning, was associated with a further increase (RR 2.54, P<0.01). Specific stereotypic and redirected behaviours were then considered as separate outcomes. Crib-biting was initiated by 10.5% of horses at median age 20 weeks, weaving by 4.6% of horses at median age 60 weeks, box-walking by 2.3% of horses at median age 64 weeks and wood-chewing by 30.3% of horses at median age 30 weeks. Wood-chewing developed at a lower rate in horses born to subordinate or mid-ranking mares than in horses born to dominant mares (RR 0.29, P<0.01; RR 0.41, P<0.01, respectively), and at a higher rate in horses kept in barns or stables rather than at grass after weaning (RR 4.49, P<0.001; RR 1A6, P<0.001, respectively). Feeding concentrates after weaning was associated with a 4-fold increase in the rate of development of crib-biting (RR 4.12, P = 0.02). The results of this study support the idea that simple changes in feeding, housing and weaning practices could substantially lower the incidence of abnormal behaviour in young horses. |
Address |
University of Bristol, Department of Clinical Veterinary Science, Langford, Bristol, UK |
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English |
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0425-1644 |
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Notes |
PMID:12357996 |
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no |
Call Number |
refbase @ user @ |
Serial |
84 |
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Author |
McGreevy, P.; Berger, J.; De Brauwere, N.; Doherty, O.; Harrison, A.; Fiedler, J.; Jones, C.; McDonnell, S.; McLean, A.; Nakonechny, L.; Nicol, C.; Preshaw, L.; Thomson, P.; Tzioumis, V.; Webster, J.; Wolfensohn, S.; Yeates, J.; Jones, B |
Title |
Using the Five Domains Model to Assess the Adverse Impacts of Husbandry, Veterinary, and Equitation Interventions on Horse Welfare. |
Type |
Journal Article |
Year |
2018 |
Publication |
Animals |
Abbreviated Journal |
Animals |
Volume |
8 |
Issue |
3 |
Pages |
41 |
Keywords |
horse; welfare assessment; equitation; husbandry; five domains |
Abstract |
The aim of this study was to conduct a series of paper-based exercises in order to assess the negative (adverse) welfare impacts, if any, of common interventions on domestic horses across a broad range of different contexts of equine care and training. An international panel (with professional expertise in psychology, equitation science, veterinary science, education, welfare, equestrian coaching, advocacy, and community engagement; n = 16) met over a four-day period to define and assess these interventions, using an adaptation of the domain-based assessment model. The interventions were considered within 14 contexts: C1 Weaning; C2 Diet; C3 Housing; C4 Foundation training; C5 Ill-health and veterinary interventions (chiefly medical); C6 Ill-health and veterinary interventions (chiefly surgical); C7 Elective procedures; C8 Care procedures; C9 Restraint for management procedures; C10 Road transport; C11 Activity—competition; C12 Activity—work; C13 Activity—breeding females; and C14 Activity—breeding males. Scores on a 1–10 scale for Domain 5 (the mental domain) gathered during the workshop were compared with overall impact scores on a 1–10 scale assigned by the same panellists individually before the workshop. The most severe (median and interquartile range, IQR) impacts within each context were identified during the workshop as: C1 abrupt, individual weaning (10 IQR 1); C2 feeding 100% low-energy concentrate (8 IQR 2.5); C3 indoor tie stalls with no social contact (9 IQR 1.5); C4 both (i) dropping horse with ropes (9 IQR 0.5) and forced flexion (9 IQR 0.5); C5 long-term curative medical treatments (8 IQR 3); C6 major deep intracavity surgery (8.5 IQR 1); C7 castration without veterinary supervision (10 IQR 1); C8 both (i) tongue ties (8 IQR 2.5) and (ii) restrictive nosebands (8 IQR 2.5); C9 ear twitch (8 IQR 1); C10 both (i) individual transport (7.00 IQR 1.5) and group transport with unfamiliar companions (7 IQR 1.5); C11 both (i) jumps racing (8 IQR 2.5) and Western performance (8 IQR 1.5); C12 carriage and haulage work (6 IQR 1.5); C13 wet nurse during transition between foals (7.5 IQR 3.75); and C14 teaser horse (7 IQR 8). Associations between pre-workshop and workshop scores were high, but some rankings changed after workshop participation, particularly relating to breeding practices. Domain 1 had the weakest association with Domain 5. The current article discusses the use of the domain-based model in equine welfare assessment, and offers a series of assumptions within each context that future users of the same approach may make when assessing animal welfare under the categories reported here. It also discusses some limitations in the framework that was used to apply the model. |
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Equine Behaviour @ team @ |
Serial |
6606 |
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Author |
McGreevy, P.D.; French, N.P.; Nicol, C.J. |
Title |
The prevalence of abnormal behaviours in dressage, eventing and endurance horses in relation to stabling |
Type |
Journal Article |
Year |
1995 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
Volume |
137 |
Issue |
2 |
Pages |
36-37 |
Keywords |
Animal Husbandry/*methods; Animals; *Behavior, Animal; Horse Diseases/*psychology; Horses; *Physical Conditioning, Animal; Prevalence; Questionnaires; *Stereotyped Behavior |
Abstract |
The behaviour of horses competing in different disciplines was studied and the relationship between the time they spent out of the stable and the prevalence of abnormal behaviour was examined. The owners of dressage, eventing and endurance horses were sent a questionnaire and a total of 1101 responses were received, giving data on 1750 horses. The behaviours studied were wood-chewing, weaving, crib-biting/wind-sucking and box-walking. The reported percentage prevalences of abnormal behaviour for the dressage, eventing and endurance horses were 32.5, 30.8 and 19.5, respectively. The relationship between the time spent in the stable and the prevalence of abnormal behaviour was examined by chi 2 tests which showed that there were significant linear trends for the eventing group (P < 0.001) and the dressage group (P < 0.05). It is concluded that the time a horse spends out of the stable is related to the discipline for which it is being trained and in dressage and eventing horses the time spent in a stable is correlated with an increased risk of abnormal behaviour. |
Address |
University of Bristol, Department of Clinical Veterinary Science, Langford |
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English |
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ISSN |
0042-4900 |
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PMID:8525580 |
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no |
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refbase @ user @ |
Serial |
89 |
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Author |
Lindberg, A.C.; Kelland, A.; Nicol, C.J. |
Title |
Effects of observational learning on acquisition of an operant response in horses |
Type |
Journal Article |
Year |
1999 |
Publication |
Applied Animal Behaviour Science |
Abbreviated Journal |
Appl. Anim. Behav. Sci. |
Volume |
61 |
Issue |
3 |
Pages |
187-199 |
Keywords |
Horse; Observational learning; Stereotyped behaviour; Operant behaviour; Breed influence; Age influence |
Abstract |
The effect of observational learning on the acquisition of an operant response was examined in eighteen riding horses and ponies. The test horses were randomly divided into three groups of six and individually exposed to one of three treatments. An additional horse was trained as a demonstrator, to perform the operant response. The observer horses watched either the demonstrator performing the bin-opening response (Group D+B); the demonstrator standing passively (Group D); or the operant bin in the absence of the demonstrator (Group B). Observers had access to and were free to interact with an identical bin during testing. Observers in Groups D+B and D were socially familiar with the demonstrator. Each test horse was tested once a day for 10 days. An ANOVA revealed no significant differences between treatment groups in the number of responses or the time taken to reach the learning criterion. However, there were highly significant differences between breed types, with non-warmbloods performing more bouts of opening the bin and feeding (p=0.02), feeding from the bin sooner (p=0.01) and reaching the criterion for learning sooner than warmbloods (p=0.05). There was also a significant negative linear relationship between horses' ages and time spent investigating the bin, with younger horses performing more investigative behaviour (y=-3.08x+106.86; p=0.02). |
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refbase @ user @ |
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562 |
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Author |
Nicol, C.J.; Badnell-Waters, A.J.; Bice, R.; Kelland, A.; Wilson, A.D.; Harris, P.A. |
Title |
The effects of diet and weaning method on the behaviour of young horses |
Type |
Journal Article |
Year |
2005 |
Publication |
Applied Animal Behaviour Science |
Abbreviated Journal |
Appl. Anim. Behav. Sci. |
Volume |
95 |
Issue |
3-4 |
Pages |
205-221 |
Keywords |
Horse; Diet; Weaning; Temperament test |
Abstract |
The effects of diet on horse behaviour have not previously been quantified in detail. In this study, we examined the behaviour of 17 foals from the age of 2 to 40 weeks. Each foal received either a starch and sugar (SS) diet or a fat and fibre (FF) diet. The two diets contained similar digestible energy, crude protein and micronutrients, but differed in the fat and non-structural carbohydrate balance. The baseline behaviour of the foals was observed every 2 weeks by focal animal sampling. Additional behavioural observations were conducted when the foals were weaned by one of two methods. Approximately 2 months after weaning, the temperament and tractability of the young horses was assessed using standardised tests. Responses to a novel object, to a novel person, and during a handling test were observed and quantified. Horses grew well on both diets with no apparent effects of diet on growth rate or baseline behaviour. Immediately after weaning, horses receiving the FF diet cantered less frequently (F = 5.10; p < 0.05), for a shorter duration (F = 7.23; p < 0.05) and appeared to be more settled. Foals that were barn-weaned appeared more stressed than foals that were paddock-weaned. In the temperament tests, horses receiving the FF diet spent significantly more time investigating (F = 6.78; p < 0.05), and less time looking at (F = 7.93; p < 0.05), the novel object than horses receiving the SS diet. They also spent less time walking away from the novel person (F = 5.16; p < 0.05) and their time taken to complete the handling test was significantly lower (F = 8.72; p = 0.01). Overall, the horses that received the FF diet appeared less distressed immediately after weaning and seemed calmer and more inquisitive during a range of temperament tests. |
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Equine Behaviour @ team @ |
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3642 |
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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 |
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 |
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1096-6080 |
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PMID:15456926 |
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no |
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refbase @ user @ |
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71 |
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