9 results match your criteria pyrazole-induced oxidative

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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

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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

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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

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October 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

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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

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Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity.

Toxicol Appl Pharmacol 2006 Oct 1;216(2):282-92. Epub 2006 Jul 1.

Department of Pharmacology and Biological Chemistry, Box 1603, One Gustave L. Levy Place, Mount Sinai School of Medicine, New York, NY 10029, USA.

Polyunsaturated fatty acids such as arachidonic acid (AA) play an important role in alcohol-induced liver injury. AA promotes toxicity in rat hepatocytes with high levels of cytochrome P4502E1 and in HepG2 E47 cells which express CYP2E1. Nitric oxide (NO) participates in the regulation of various cell activities as well as in cytotoxic events. Read More

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October 2006

Opposite action of S-adenosyl methionine and its metabolites on CYP2E1-mediated toxicity in pyrazole-induced rat hepatocytes and HepG2 E47 cells.

Am J Physiol Gastrointest Liver Physiol 2006 Apr 23;290(4):G674-84. Epub 2005 Nov 23.

Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.

S-adenosyl-L-methionine (SAMe) is protective against a variety of hepatotoxins, including ethanol. The ability of SAMe to protect against cytochrome P-450 2E1 (CYP2E1)-dependent toxicity was studied in hepatocytes from pyrazole-treated rats and HepG2 E47 cells, both of which actively express CYP2E1. Toxicity was initiated by the addition of arachidonic acid (AA) or by depletion of glutathione after treatment with L-buthionine sulfoximine (BSO). Read More

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Microsomal oxidation of N,N-diethylformamide and its effect on P450-dependent monooxygenases in rat liver.

Chem Res Toxicol 1996 Jul-Aug;9(5):882-90

Laboratory of Genetic and Biochemical Toxicology, Istituto di Mutagenesi e Differenziamento, C.N.R., Pisa, Italy.

N,N-Diethylformamide (DEF) is a hepatotoxic polar solvent in which metabolism has not been investigated. In this study we examined the following: (a) the oxidative metabolism of DEF using both liver microsomes from rats pretreated with selected P450 inducers and purified P450 enzyme (2B1, 2E1, 2C11); and (b) the effect of administration of DEF and its metabolite, the monoethylformamide (MEF), on induction and/or inhibition of the P450 isoforms in rats. DEF was deethylated by microsomal P450-dependent oxidation forming acetaldehyde and MEF according to Michaelis-Menten kinetic parameters. Read More

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December 1996

An investigation of the metabolism of N-nitroso-N-methylaniline by phenobarbital- and pyrazole-induced Sprague-Dawley rat liver and esophagus derived S-9.

Chem Biol Interact 1987 Mar;61(3):215-28

The metabolism and mutagenicity of the esophageal carcinogen N-nitroso-N-methylaniline (NMA) was studied using hepatic and esophageal 9000 X g supernatant (S-9) preparations from Sprague-Dawley rats induced with pyrazole and phenobarbital. Only pyrazole-induced hepatic S-9 was able to dose-dependently activate NMA to a mutagen in the Ames assay and specifically in Salmonella typhimurium TA1537. NMA in the presence of phenobarbital-induced S-9 gave a very weak non-dose dependent mutagenic response. Read More

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