Dec 4, 2008

Moderate hypothermia prevents cardiac arrest-mediated suppression of drug metabolism and induction of interleukin-6 in rats

Critical Care Medicine
Michael A TortoriciSamuel M Poloyac

Abstract

Therapeutic hypothermia is being clinically used to reduce neurologic deficits after cardiac arrest (CA). Patients receiving hypothermia after CA receive a wide-array of medications. During hypothermia, drug metabolism is markedly reduced. Little, however, is known about the impact of hypothermia on drug metabolism after rewarming. The objective of this study was to examine the effect of CA and hypothermia on the functional regulation of two major drug metabolizing cytochrome P450 (CYP) isoforms. Laboratory investigation. University pharmacy school and animal research facility. Thirty-six male Sprague-Dawley rats. Hypothermia was induced via surface cooling in a rat CA model and maintained for 3 hrs. Animals were killed at 5 or 24 hrs and liver was analyzed for hepatic activity and mRNA expression of CYP3A2 and CYP2E1. Plasma interleukin-6 (IL-6) concentrations were determined. The effect of IL-6 on pregnane X receptor-mediated transcription of the rat CYP3A2 promoter was evaluated via luciferase reporter in HepG2 cells. At 24 hrs after CA a decrease in CYP3A2 and CYP2E1 activity was observed, 55.7% +/- 12.8% and 46.8% +/- 29.7% of control, respectively (p < 0.01). CA decreased CYP3A2 mRNA (p < 0.05), but not CYP2E1 mRNA. Expre...Continue Reading

  • References34
  • Citations12

References

  • References34
  • Citations12

Citations

Mentioned in this Paper

Neurologic Manifestations
Enzymes, antithrombotic
Cytochrome P450
CYP2E1 gene
Xenobiotic Monooxygenases
Hepatic
Promoter
Cytochrome P450 3A
Rats, Sprague-Dawley
Cytochrome P-450 CYP2E1

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Head And Neck Squamous Cell Carcinoma

Squamous cell carcinomas account for >90% of all tumors in the head and neck region. Head and neck squamous cell carcinoma incidence has increased dramatically recently with little improvement in patient outcomes. Here is the latest research on this aggressive malignancy.

Signaling in Adult Neurogenesis

Neural stem cells play a critical role in the production of neuronal cells in neurogenesis is of great importance. Of interest is the role signalling mechanisms in adult neurogenesis. Discover the latest research on signalling in adult neurogenesis.

Psychiatric Chronotherapy

Psychiatric Chronotherapy considers the circadian rhythm as a major factor for optimizing therapeutic efficacy of psychiatric interventions. Discover the latest research on Psychiatric Chronotherapy here.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.