The Metabolism of Xenobiotics by Certain Extrahepatic Organs and its Relation to Toxicity*

Sex-dependent expression of CYP2C11 in spleen, thymus and bone marrow regulated by growth hormone

“…Whereas the liver clearly contains the highest content of total P450s, isoforms are expressed in kidney, gut, lung, skin, placenta, blood vessels and likely every cell in every organ system [1][2][3]. These extra hepatic tissues are often the target sites for therapeutic intervention against localized pathologies like cancer, infections and inflammations that coincidentally can result in toxicities arising from the biotransformation of the administered drug(s) [3,4].…”

“…These extra hepatic tissues are often the target sites for therapeutic intervention against localized pathologies like cancer, infections and inflammations that coincidentally can result in toxicities arising from the biotransformation of the administered drug(s) [3,4]. Consequently, the content of tissue-specific P450 isoforms may represent an important parameter determining both the therapeutic efficacy and susceptibility to the toxic effects of administered xenobiotics.…”

The immunocytochemical localisation and distribution of cytochrome P‐ 450 in normal human hepatic and extrahepatic tissues with a monoclonal antibody to human cytochrome P‐450.

“…The various forms of cytochrome P-450 have diverse substrate specificities and responses to inducing agents (Guengerich et al, 1982;Le Provost et al, 1983;Burke et al, 1985). The balance of metabolic activation and detoxification of drugs and other chemicals by individual forms of cytochrome P-450 in different tissues is an important factor in explaining organ-specific toxicity (Gram et al, 1986). Cytochrome P-450 and its associated monooxygenase activities are found predominantly in the liver, but are also present in many extrahepatic tissues although usually at lower levels than in the liver (Burke & Orrenius, 1979;Gram et al, 1986).…”

A Frameshift Mutation and Alternate Splicing in Human Brain Generate a Functional Form of the Pseudogene Cytochrome P4502D7 That Demethylates Codeine to Morphine

“…However, the potential to generate active metabolite(s) at the site of action has generated interest in extrahepatic P450. This has prompted extensive investigations into the xenobiotic metabolizing capability of extrahepatic organs, such as lung, kidney, skin, and nasal epithelium, and the far reaching consequences of such metabolism, in situ, within specific cells in target organs have been recognized in laboratory animals (2) and humans (3). The preferential localization of drug-metabolizing enzymes within specific cell types in these organs renders such cells significantly capable of metabolizing drugs (4).…”

“…Over the past decade studies from our laboratory and others have demonstrated the presence of a competent microsomal P450 system in the rodent (2,9,10) and human (3,11) brain and its ability to metabolize a variety of xenobiotics. The appearance of multiple forms of P450 in brain and their selective inducibility by a variety of drugs and xenobiotics have also been identified (9,(12)(13)(14).…”