Abstract
Many developmental toxicants and teratogens require prior metabolism to reactive species or free radicals to exert toxicity. Thus the knowledge of conceptal biotransformation is absolutely critical in understanding toxicity of these chemicals. Due to extremely low content of cytochrome P450 in the embryo and other conceptal tissues, the research focus in recent years has steadily shifted toward enzymes capable of peroxidative oxidation of xenobiotics. At least three enzymes viz. lipoxygenase, peroxidase and prostaglandin synthase, each capable of peroxidative xenobiotic metabolism, occur in conceptal tissues of man and laboratory animals in biologically significant amounts. This review mainly summarizes the available information on the enzymatic bioactivation of teratogens and developmental toxicants belonging to diverse classes such as drugs, pesticides, environmental contaminants, industrial and other chemicals. Additionally, some discussion is devoted toward issues such as drug-drug interactions. The emerging new information on the peroxidative glutathione conjugate formation from xenobiotics is also presented. A critical need for gathering more information on this subject using different enzyme preparations from human conceptal tissues is stressed to avoid tragedies in the future.
Keywords: lipoxygenase (LO), flavin-containing monooxygenase (MFMO), LIPID PEROXIDATION-COUPLED CO-OXIDATION, PROSTAGLANDIN SYNTHASE (PGS), LIPOXYGENASE, PEROXIDASE
Current Pharmaceutical Design
Title: Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals
Volume: 7 Issue: 9
Author(s): Arun P. Kulkarni
Affiliation:
Keywords: lipoxygenase (LO), flavin-containing monooxygenase (MFMO), LIPID PEROXIDATION-COUPLED CO-OXIDATION, PROSTAGLANDIN SYNTHASE (PGS), LIPOXYGENASE, PEROXIDASE
Abstract: Many developmental toxicants and teratogens require prior metabolism to reactive species or free radicals to exert toxicity. Thus the knowledge of conceptal biotransformation is absolutely critical in understanding toxicity of these chemicals. Due to extremely low content of cytochrome P450 in the embryo and other conceptal tissues, the research focus in recent years has steadily shifted toward enzymes capable of peroxidative oxidation of xenobiotics. At least three enzymes viz. lipoxygenase, peroxidase and prostaglandin synthase, each capable of peroxidative xenobiotic metabolism, occur in conceptal tissues of man and laboratory animals in biologically significant amounts. This review mainly summarizes the available information on the enzymatic bioactivation of teratogens and developmental toxicants belonging to diverse classes such as drugs, pesticides, environmental contaminants, industrial and other chemicals. Additionally, some discussion is devoted toward issues such as drug-drug interactions. The emerging new information on the peroxidative glutathione conjugate formation from xenobiotics is also presented. A critical need for gathering more information on this subject using different enzyme preparations from human conceptal tissues is stressed to avoid tragedies in the future.
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Cite this article as:
Kulkarni P. Arun, Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals, Current Pharmaceutical Design 2001; 7 (9) . https://dx.doi.org/10.2174/1381612013397735
DOI https://dx.doi.org/10.2174/1381612013397735 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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