13 results match your criteria mice pyrazole-induced

  • Page 1 of 1

CYP2E1 potentiates toxicity in obesity and after chronic ethanol treatment.

Drug Metabol Drug Interact 2012 ;27(3):125-44

Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA.

CYP2E1 activates several hepatotoxins and contributes to alcoholic liver damage. In this report, we review our studies on whether induction of CYP2E1 can potentiate liver injury in obesity. Acetone- or pyrazole-induced severe liver injury in obese mice as compared to obese controls and lean mice. Read More

View Article and Full-Text PDF
November 2012

Peroxiredoxin III and sulfiredoxin together protect mice from pyrazole-induced oxidative liver injury.

Antioxid Redox Signal 2012 Nov 31;17(10):1351-61. Epub 2012 May 31.

Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.

Aims: To define the mechanisms underlying pyrazole-induced oxidative stress and the protective role of peroxiredoxins (Prxs) and sulfiredoxin (Srx) against such stress.

Results: Pyrazole increased Srx expression in the liver of mice in a nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent manner and induced Srx translocation from the cytosol to the endoplasmic reticulum (ER) and mitochondria. Pyrazole also induced the expression of CYP2E1, a primary reactive oxygen species (ROS) source for ethanol-induced liver injury, in ER and mitochondria. Read More

View Article and Full-Text PDF
November 2012

Pyrazole induced oxidative liver injury independent of CYP2E1/2A5 induction due to Nrf2 deficiency.

Toxicology 2008 Oct 3;252(1-3):9-16. Epub 2008 Aug 3.

Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.

Pyrazole can induce CYP2E1 and 2A5, which produce reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates important antioxidant enzymes to remove ROS. In this study, we applied Nrf2 knockout mice to test the hypothesis that pyrazole will cause hepatotoxicity and elevate oxidative stress to a greater extent in Nrf2 knockout mice compared to wild type mice. Read More

View Article and Full-Text PDF
October 2008

Microarray analysis of hepatic gene expression in pyrazole-mediated hepatotoxicity: identification of potential stimuli of Cyp2a5 induction.

Biochem Pharmacol 2008 Jan 14;75(2):538-51. Epub 2007 Sep 14.

Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

Cytochrome P450 2a5 (Cyp2a5) expression is induced during liver damage caused by hepatotoxins such as pyrazole, however, the mechanism underlying this overexpression is unclear. In order to identify pathophysiological and cellular responses to pyrazole that might alter Cyp2a5 expression, we examined the effect of pyrazole on mouse hepatic gene expression in C57BL/6 mice using Affymetrix 430 2.0 microarrays. Read More

View Article and Full-Text PDF
January 2008

Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice.

Hepatology 2007 Jun;45(6):1355-65

Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.

Unlabelled: Cytochrome P450 2E1 (CYP2E1) activates several hepatotoxins and contributes to alcoholic liver damage. Obesity is a growing health problem in the United States. The aim of the present study was to evaluate whether acetone- or pyrazole-mediated induction of CYP2E1 can potentiate liver injury in obesity. Read More

View Article and Full-Text PDF

S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury.

Am J Physiol Gastrointest Liver Physiol 2007 Jul 19;293(1):G91-103. Epub 2007 Apr 19.

Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.

Pyrazole treatment to induce cytochrome P-450 2E1 (CYP2E1) was recently shown to cause liver injury in ob/ob mice but not in lean mice. The present study investigated the effects of S-adenosyl-l-methionine (SAM) on the CYP2E1-dependent liver injury in ob/ob mice. Pyrazole treatment of ob/ob mice for 2 days caused necrosis, steatosis, and elevated serum transaminase and triglyceride levels compared with saline ob/ob mice. Read More

View Article and Full-Text PDF

Regulation of the cytochrome P450 2A genes.

Authors:
Ting Su Xinxin Ding

Toxicol Appl Pharmacol 2004 Sep;199(3):285-94

Division of Cell and Molecular Biology, Department of Biology, Boston University, MA 02215, USA.

Cytochrome P450 monooxygenases of the CYP2A subfamily play important roles in xenobiotic disposition in the liver and in metabolic activation in extrahepatic tissues. Many of the CYP2A transcripts and enzymes are inducible by xenobiotic compounds, and the expression of at least some of the CYP2A genes is influenced by physiological status, such as circadian rhythm, and pathological conditions, such as inflammation, microbial infection, and tumorigenesis. Variability in the expression of the CYP2A genes, which differs by species, animal strain, gender, and organ, may alter the risks of chemical toxicity for numerous compounds that are CYP2A substrates. Read More

View Article and Full-Text PDF
September 2004

NTP technical report on the toxicity and metabolism studies of chloral hydrate (CAS No. 302-17-0). Administered by gavage to F344/N rats and B6C3F1 mice.

Authors:
F A Beland

Toxic Rep Ser 1999 Aug(59):1-66, A1-E7

Chloral hydrate is widely used as a sedative and a hypnotic in pediatric medicine. It is also a byproduct of water chlorination. Chloral hydrate has been shown to be genotoxic in numerous prokaryotic and eukaryotic assay systems including human lymphocytes in vitro. Read More

View Article and Full-Text PDF

Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung, olfactory mucosa, and small intestine, but not in the heart.

Drug Metab Dispos 2000 Nov;28(11):1311-6

Wadsworth Center, New York State Department of Health and School of Public Health, State University of New York at Albany, Albany, New York 12201-0509, USA.

We have recently shown that rat CYP2J4 is inducible by pyrazole in liver, small intestine, and olfactory mucosa. The aim of the present study was to determine whether mouse CYP2Js are also inducible by pyrazole, which was known to induce CYP2A5 in mouse liver and kidney, but not in lung or olfactory mucosa. CYP2J proteins were detected in mouse liver, lung, kidney, heart, eye, olfactory mucosa, and small intestine by immunoblot analysis with an anti-CYP2J4 antibody. Read More

View Article and Full-Text PDF
November 2000

Metabolic interactions of methoxsalen and coumarin in humans and mice.

Biochem Pharmacol 1994 Oct;48(7):1363-9

Department of Pharmacology and Toxicology, University of Oulu, Finland.

Methoxsalen (8-methoxypsoralen) is a very potent inhibitor of human cytochrome P450 2A6 (CYP2A6) and mouse Cyp2a-5-mediated coumarin 7-hydroxylation in vitro. To determine the effect of methoxsalen on coumarin 7-hydroxylation in humans in vivo, five subjects were given 45 mg of methoxsalen and 5 mg of coumarin. Methoxsalen inhibited in vivo coumarin metabolism by 47 +/- 9. Read More

View Article and Full-Text PDF
October 1994

Posttranscriptional regulation of coumarin 7-hydroxylase induction by xenobiotics in mouse liver: mRNA stabilization by pyrazole.

Authors:
K Aida M Negishi

Biochemistry 1991 Aug;30(32):8041-5

Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.

The induction mechanism by pyrazole or phenobarbital of coumarin 7-hydroxylase (cytochrome P450coh) was investigated in DBA/2J male mice. The P450coh mRNA in the pyrazole-induced mice was increased gradually to a 20-fold higher level within 48 h, yet transcription of the P450coh gene was not affected. The half-life of P450coh mRNA, on the other hand, was at least 4-fold longer in the pyrazole-induced DBA/2J (approximately 6. Read More

View Article and Full-Text PDF

Mouse liver phenobarbital-inducible P450 system: purification, characterization, and differential inducibility of four cytochrome P450 isozymes from D2 mouse.

Arch Biochem Biophys 1989 Aug;273(1):42-57

Department of Pharmacology and Toxicology, University of Kuopio, Finland.

Three novel cytochrome P450 isozymes were purified from phenobarbital (PB)-treated D2 mouse liver microsomes and compared to the previously characterized coumarin 7-hydroxylase, P450Coh. The molecular masses were 56.5, 55, 51, and 49. Read More

View Article and Full-Text PDF

Pharmacological and toxicological properties of 4-hydroxypyrazole, a metabolite of pyrazole.

Acta Pharmacol Toxicol (Copenh) 1981 May;48(5):418-23

The effects of 4-hydroxypyrazole (4-HP), a principal metabolite of pyrazole, were studied in mice. The compound was toxic, much more so than pyrazole with an LD50 of 1.1 mmol/kg (92 mg/Kg) and doses greater than 1. Read More

View Article and Full-Text PDF
  • Page 1 of 1