Decreased Constitutive Murine Cytochromes P450 by Staphyloccocal Enterotoxin-B (SEB)

Details

• Personal Author:
  Scheurer J ; Shedlofsky SI ; Snawder, John E. ; Tosheva R
• Description:
  Inflammation caused by gram-negative endotoxin (LPS) is associated with impaired hepatic P450-mediated drug metabolizing activity. However, gram-positive bacteria also commonly cause the sepsis syndrome. To evaluate effects of the gram-positive inflammatory stimulant SEB, C3H/HeN mice (male, 25g) were injected ip with either saline, LPS (0.5mg/kg), or SEB (3mg/kg), and hepatic microsomes prepared and serum harvested 24h later. Serum amyloid A (SAA) measured the intensity of the hepatic acute phase response. Total spectral P450, ethoxyresorufin-O-deethylase (EROD, -CYP1A1/2), paranitrophenol-OHase (PNP -CYP2El), and benzyloxy-O-deethylase (BROD -CYP3A) were assayed and immunoblots for each P450 isoform prepared using commercial antibodies. Data are mean +/-SD for 4-7 mice in each group. SEB increased SAA and decreased total P450 to the same ex­tent as LPS and also depressed activities of each specific P450 isoform and amount of specific protein > or = LPS. 3mg/kg was as effective as 6mg/kg and a time course showed maximal depression at 24h. Conclusion: The gram-positive inflammatory stimulant SEB depresses hepatic P450s as well as LPS. This suggests that patients with gram-positive sepsis are likely to have impaired hepatic drug metabolism. [Description provided by NIOSH]
• Subjects:
  Biochemistry Biological Factors Endotoxins Energy Metabolism Environmental Monitoring Laboratories Liver Occupational Health Safety
• Keywords:
  Biological-effects Biological-factors Biological-monitoring Cell-biology Cellular-reactions Dose-response Drug-interaction Exposure-assessment Exposure-methods Hepatic-microsomal-enzymes Hepatocytes Hepatotoxicity Hepatotoxins Laboratory-animals Laboratory-testing Liver-cells Liver-disorders Liver-microsomal-metabolism Metabolic-disorders Metabolic-study Molecular-biology

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• ISSN:
  0270-9139
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DBBS - Division of Biomedical and Behavioral Sciences
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  22
• Issue:
  4
• NIOSHTIC Number:
  nn:20035137
• Citation:
  Hepatology 1995 Oct; 22(4)(Suppl S Part 2):246A
• Federal Fiscal Year:
  1996
• Peer Reviewed:
  False
• Part Number:
  2
• Source Full Name:
  Hepatology
• Supplement:
  S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:722ce08f98b8186ca10c2c6a01423330958c59dfbe400d5dd4158c8cc272b7e780ea158c3ff79c06d9257d704ce3d6b8447330371b94f9d3be8c4f86b06b92d3
• Download URL:
  https://stacks.cdc.gov/view/cdc/187091/cdc_187091_DS1.pdf
• File Type:
  [PDF - 257.14 KB ]