Halothane-induced lipid peroxidation and glucose-6-phosphatase inactivation in microsomes under hypoxic conditions.

Abstract:

:Halothane-induced lipid peroxidation was studied in microsomes from phenobarbital-pretreated male rats at defined steady state oxygen partial pressures (PO2). At PO2 less than 10 mmHg on addition of halothane to NADPH-reduced microsomes, significant increases in malondialdehyde (MDA) formation, oxygen uptake, and conjugated dienes were measured. At the maximum, near a PO2 of 1 mmHg, halothane induced the formation of about 0.75 nmol MDA X mg microsomal protein-1 X min-1; it also stimulated microsomal oxygen uptake twofold to threefold, and caused an almost threefold increase in conjugated diene absorption. Moreover, at this PO2 microsomal glucose-6-phosphatase lost about 70% of its activity. At PO2 greater than 10 mmHg, no significant effects of halothane on MDA formation, oxygen uptake, conjugated diene absorption, and glucose-6-phosphatase activity were observed; likewise under anaerobic conditions there was only a slight increase in conjugated dienes. The findings demonstrate that halothane induces microsomal lipid peroxidation at low PO2 and in the presence of particular cytochrome P-450 isoenzymes, and that the halothane-induced lipid peroxidation leads to severe microsomal lesions, as indicated by the loss of glucose-6-phosphatase activity.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

de Groot H,Noll T

doi

10.1097/00000542-198501000-00009

subject

Has Abstract

pub_date

1985-01-01 00:00:00

pages

44-8

issue

1

eissn

0003-3022

issn

1528-1175

journal_volume

62

pub_type

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