Role of biotransformation in conceptal toxicity of drugs and other chemicals.
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.
Kulkarni
A P
AP
Florida Toxicology Research Center, Department of Environmental and Occupational Health, College of Public Health, MDC-056, University of South Florida, 13201 Bruce B. Downs Boulevard, Tampa, FL 33612-3805, USA. akulkarn@coml.med.usf.edu
D000818:Animals; D001711:Biotransformation; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011247:Pregnancy; D013723:Teratogens / Q000493:pharmacokinetics* / Q000633:toxicity*; D014118:Toxins, Biological / Q000493:pharmacokinetics* / Q000633:toxicity*
D004364:Pharmaceutical Preparations; D013723:Teratogens; D014118:Toxins, Biological