TITLE

CREBH Determines the Severity of Sulpyrine-Induced Fatal Shock

AUTHOR(S)
Kamiyama, Naganori; Yamamoto, Masahiro; Saiga, Hiroyuki; Ma, Ji Su; Ohshima, Jun; Machimura, Sakaaki; Sasai, Miwa; Kimura, Taishi; Ueda, Yoshiyasu; Kayama, Hisako; Takeda, Kiyoshi
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Although the pyrazolone derivative sulpyrine is widely used as an antipyretic analgesic drug, side effects, including fatal shock, have been reported. However, the molecular mechanism underlying such a severe side effect is largely unclear. Here, we report that the transcription factor CREBH that is highly expressed in the liver plays an important role in fatal shock induced by sulpyrine in mice. CREBH-deficient mice were resistant to experimental fatal sulpyrine shock. We found that sulpyrine-induced expression of cytochrome P450 2B (CYP2B) family genes, which are involved in sulpyrine metabolism, in the liver was severely impaired in CREBH-deficient mice. Moreover, introduction of CYP2B in CREBH-deficient liver restored susceptibility to sulpyrine. Furthermore, ectopic expression of CREBH up-regulated CYP2B10 promoter activity, and in vivo knockdown of CREBH in wild-type mice conferred a significant resistance to fatal sulpyrine shock. These data demonstrate that CREBH is a positive regulator of CYP2B in response to sulpyrine administration, which possibly results in fatal shock.
ACCESSION #
87624011

 

Related Articles

  • Induction of P450 1A by 3-methylcholanthrene protects mice from aristolochic acid-I-induced acute renal injury. Xiang Xue; Ying Xiao; Hongli Zhu; Hui Wang; Yongzhen Liu; Tianpei Xie; Jin Ren // Nephrology Dialysis Transplantation;Oct2008, Vol. 23 Issue 10, p3074 

    Background. Cytochrome P450 1A, an enzyme known to metabolize polycyclic aromatic hydrocarbons (PAHs), participates in the metabolism of aristolochic acid I (AAI) in liver and kidney microsomes isolated from humans and rodents. This study was designed to investigate whether P450 1A plays a role...

  • Comparative Pharmacokinetics and Metabolism Studies in Lean and Diet-Induced Obese Mice: An Animal Efficacy Model for 11�-Hydroxysteroid Dehydrogenase Type 1 (11�-HSD1) Inhibitors. Mengmeng Wang; Xianbin Tian; Leung, Louis; Jianyao Wang; Houvig, Nicole; Xiang, Jason; Saiah, Eddine; Seung Hahm; Suri, Vipin; Xin Xu // Drug Metabolism Letters;Jan2011, Vol. 5 Issue 1, p55 

    Diet-induced obese (DIO) mice have been commonly used as an animal model in the efficacy assessment for new drug candidates. Although high-fat feeding has been reported to cause profound physiological changes, including the expression of drug-metabolizing enzymes, limited studies have been...

  • Tissue Distribution and Gender-Divergent Expression of 78 Cytochrome P450 mRNAs in Mice. Renaud, Helen J.; Cui, Julia Yue; Khan, Mohammed; Klaassen, Curtis D. // Toxicological Sciences;Dec2011, Vol. 124 Issue 2, p261 

    Cytochrome P450 (Cyp) enzymes from the first four families (Cyp1–4) play a major role in metabolizing xenobiotics, affecting drug pharmacokinetics and chemical-induced toxicity. Due to cloning of the mouse genome, many novel Cyp isoforms have been identified, but their tissue distribution...

  • Effects of CYP3A Inhibition on the Metabolism of Cilostazol. Suri, A.; Forbes, W.P.; Bramer, S.L. // Clinical Pharmacokinetics;1999 Supplement, Vol. 37 Issue 6, p61 

    Objective: In vitro results suggest that cilostazol is metabolised by cytochrome P450 (CYP) isoforms 1A2, 2D6, 3A and 2C19. This study investigated the role of CYP3A inhibition on the metabolism of cilostazol. Design: The study was conducted as a single-centre, open-label, nonrandomised,...

  • Evaluation of 170 Xenobiotics as Transactivators of Human Pregnane X Receptor (hPXR) and Correlation to Known CYP3A4 Drug Interactions. Sinz, Michael; Kim, Sean; Zhengrong Zhu; Taosheng Chen; Anthony, Monique; Dickinson, Kenneth; Rodrigues, A. David // Current Drug Metabolism;May2006, Vol. 7 Issue 4, p375 

    The human transcription factor pregnane X receptor (hPXR) is a key regulator of enzyme expression, especially cytochrome P450 3A4 (CYP3A4). Due to the prominence of CYP3A4 in the elimination of many drugs, the development of high throughput in vitro models to predict the effect of drugs on...

  • Ethanol Induction of CYP2A5: Role of CYP2E1-ROS-Nrf2 Pathway. Yongke Lu; Xu Hannah Zhang; Cederbaum, Arthur I. // Toxicological Sciences;Aug2012, Vol. 128 Issue 2, p427 

    Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1- dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same...

  • Cytochrome P450 in the Brain ; A Review. Hedlund, E.; Gustafsson, J.A.; Warner, M. // Current Drug Metabolism;Sep2001, Vol. 2 Issue 3, p245 

    After many frustrating decades of unsuccessful attempts to characterize the isoforms of P450 in the brain, several scientific breakthroughs in the 80s and 90s have resulted in major advances in our understanding of cytochromes P450 (CYP) in brain. We now know that classical CYP inducers, e.g....

  • Effect of Omeprazole on the Metabolism of Cilostazol. Suri, A.; Bramer, S.L. // Clinical Pharmacokinetics;1999 Supplement, Vol. 37 Issue 6, p53 

    Objective: In vitro results suggest that cilostazol is metabolised by cytochrome P450 (CYP) isoforms 1A2, 2D6, 3A4 and 2C19. This study was designed to evaluate the effect of concomitant administration of omeprazole (a CYP2C19 inhibitor) on the pharmacokinetics of a single 100mg oral dose of...

  • Role of CYP1A2 in the toxicity of long-term phenacetin feeding in mice. Peters, Jeffrey M.; Morishima, Hideki; Ward, Jerrold M.; Coakley, Christopher J.; Kimura, Shioko; Gonzalez, Frank J. // Toxicological Sciences;Jul1999, Vol. 50 Issue 1, p82 

    The mechanisms underlying phenacetin-induced toxicity and carcinogenicity are not clear. In particular, it is not known whether these effects are mediated by metabolic activation of the drug. CYP1A2 is known to metabolize phenacetin in vitro. To determine the role of this enzyme in vivo, the...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics