Hepatic Cytochrome P450 Profiles in Hemorrhagic Shock Model Rats After Transfusion With Stored Red Blood Cells

Masahiro Tokuno, Kazuaki Taguchi, Keishi Yamasaki, Masaki Otagiri

Research output: Contribution to journalArticle

Abstract

Red cell transfusions, which deteriorate in quality during storage, triggers several negative biological responses. However, little is known regarding the effects of stored red cell transfusion on cytochrome P450 (P450) profiles. To clarify this issue, we investigated hepatic P450 profiles in hemorrhagic shock model rats after resuscitation with stored packed red cells (PRC). The pharmacokinetics data for P450-metabolizing substrates showed that the clearance of substrates for Cyp1A2 and Cyp3A2 in the stored PRC resuscitation group were decreased compared to sham group. The protein expression, metabolic activity and mRNA expression of the P450 isoforms in the stored PRC resuscitation group were lower than the corresponding values for the sham group. However, these changes would be expected to have weak effects on the in vivo pharmacokinetics of the concomitant drugs based on the criteria stated in the guideline on drug interactions. In contrast, the results of these P450 profiles in the stored PRC and fresh PRC resuscitation group exhibited a similar trend. These results suggest that the stored PRC transfusion has an influence on the hepatic P450 profiles, but is of little clinical significance, not by the deterioration of the quality of red cells but pathophysiological alterations following the hemorrhage and transfusion.

Original languageEnglish
Pages (from-to)3490-3495
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume109
Issue number11
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Cytochrome P450
  • Disease effect
  • Hepatic metabolism
  • Pharmacokinetics
  • Phase I metabolism

ASJC Scopus subject areas

  • Pharmaceutical Science

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