Xenobiotic metabolism in brain.

Abstract:

:Recent hypothesis suggesting a role for environmental toxins in the pathogenesis of neurodegenerative disorders has stimulated interest in research on xenobiotic metabolizing capability of the brain. In addition to possible irreversible loss of neurons through bioactivation in situ in the nervous tissue, the metabolism of psychoactive drugs in the target tissue can lead to local pharmacological modulation at the site of action. The major drug metabolizing enzymes, cytochromes P-450 (P450) and flavin-containing monooxygenase (FMO) have been detected in rodent brain and human brain tissue obtained at autopsy. The brain microsomal and mitochondrial P450 systems are capable of metabolizing a variety of xenobiotics, while the brain FMO efficiently metabolizes a variety of psychoactive drugs to their respective N-oxides. Immunocytochemical studies have revealed the regional heterogeneity in the distribution of multiple forms of P450 in the brain and the co-localization of P450 and FMO predominantly in the neuronal cells. Although the brain P450 and FMO share many common features with similar enzymes present in other tissues such as liver and lung, there are some distinctive differences. It is evident from the studies carried out so far that the brain can metabolize a variety of lipophilic xenobiotics that enter by way of the blood stream.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Ravindranath V,Bhamre S,Bhagwat SV,Anandatheerthavarada HK,Shankar SK,Tirumalai PS

doi

10.1016/0378-4274(95)03508-7

subject

Has Abstract

pub_date

1995-12-01 00:00:00

pages

633-8

eissn

0378-4274

issn

1879-3169

pii

0378-4274(95)03508-7

journal_volume

82-83

pub_type

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