The Mechanism of Phenobarbitone Potentiation of Centrilobular Hepatic Necrosis

  • Martyn T. Smith
  • Eric D. Wills
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


The pre-treatment of rats with phenobarbitone markedly potentiates both the incidence and severity of the centrilobular hepatic necrosis caused by reactive intermediates of foreign compounds such as paracetamol, phenacetin and halogenated aromatic hydrocarbons (Brodie et al.,1971; Mitchell et al.,1976) These reactive intermediates are formed mainly as a result of mixed function oxidase activity, involving cytochrome P-450, and the liver is normally protected against their toxicity by reduced glutathione (GSH) (Mitchell et al.,1973). Phenobarbitone could therefore potentiate the level of centrilobular hepatic necrosis by:
  1. (a)

    selectively increasing the concentration of cytochrome P-450 and the activity of the mixed-function oxidase in the centrilobular hepatocytes, or

  2. (b)

    selectively lowering the concentration of GSH in the centrilobular hepatocytes.



Toxic Metabolite G6PD Activity Foreign Compound Periportal Hepatocyte Periportal Region 
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Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Martyn T. Smith
    • 1
  • Eric D. Wills
    • 1
  1. 1.Biochemistry DepartmentThe Medical College of St. Bartholomew’s HospitalLondonUK

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