Factors Determining the Teratogenicity of Drugs

Wilson, James G.

doi:10.1146/annurev.pa.14.040174.001225

Cited by 13 publications

(2 citation statements)

References 45 publications

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“…It is increasingly recognized that the placenta and possibly some foetal organs contain enzymes capable to catalyze the biotransformation of drug substrates (Szeto 1982), and that such reactions could play a role in the determination of the transplacental movement rates of certain drugs (Wilson 1974). Drugs are agents that affect the function of the living systems by action at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

Drug‐metabolizing Enzymes in the Placenta and Foetus of Camel and Sheep

Homeida

Al-Eknah

Dafalla

1993

Reprod Domestic Animals

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Contents The activities of cytochrome P‐450 and the P‐450 dependent aminopyrine ‐N‐demethylase and aniline 4‐hydroxylase (Phase I, drugmetabolizing enzymes) and UDP‐glucurony‐l‐transferase (a Phase II drug‐metabolizing enzyme) have been measured in vitro in the placenta and liver of camels and sheep during pregnancy. The placenta of late pregnancy of both species produced 50% of the activity in maternal liver of phase I drug‐metabolizing enzymes. The rate of O‐aminophenol glucuronide was low both in placenta and foetal liver. It is suggested that close to term the placenta and foetal liver are capable of metabolizing drugs by P‐450 mediated phase I reactions. Inhalt: Arzneimittel‐metabolisierende Enzyme von Plazenta und Fötus bei Kamel und Schaf Während der Trächtigkeit wurde die Aktivität der Cytochrom P‐450 abhängigen Aminophyrine ‐N‐Demethylase, Anilin 4‐Hydroxylase (Phase I metabolisierendes Enzym) und der UDP‐Glucuronyl‐1 Transferase (Phase II metabolisierendes Enzym) unter in vitro Bedingungen in Plazenta‐ und Lebergewebe von Kamelen und Schafen gemessen. In beiden Tierarten produzierte die Plazenta während der späten Trächtigkeit 50% der Aktivität, wie sie die mütterliche Plazenta der “Phase I—Enzyme” produziert. Die O‐Aminophenol Glucuronide waren dagegen gering in Plazenta und fetaler Leber. Es wird angenommen, daβ die Plazenta und die fetale Leber kurz vor der Geburt in der Lage sind, Arzneimittel durch die Cytochrom P‐450 abhängige Phase I‐Reaktionen zu metabolisieren.

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Section: Introductionmentioning

confidence: 99%

Drug‐metabolizing Enzymes in the Placenta and Foetus of Camel and Sheep

Homeida

Al-Eknah

Dafalla

1993

Reprod Domestic Animals

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“…Several recent reviews dealt with general aspects of reproductive toxicology (1, 7) and gonadal metabolism (12). An ever-expanding literature is devoted to teratology (13)(14)(15)(16)(17). Reproductive effects of occupational exposures have been considered (18)(19)(20)(21).…”

mentioning

confidence: 99%

Biological markers of male reproductive toxicology.

Mattison

1987

Environ Health Perspect

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Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals.

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The Mechanisms of Action of Reproductive Toxins

Mattison

1983

American J Industrial Med

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A general discussion of the mechanisms of action of reproductive toxins is presented. Reproductive toxicants may produce their adverse effects by one of several mechanisms. Some xenobiotics may act directly, either by virtue of chemical reactivity (eg, oocyte destruction by alkylating agents) or by structural similarity to endogenous molecules (eg, hormone antagonists). Other xenobiotics interrupt reproductive processes indirectly either by metabolic processing to a direct-acting toxicant (eg, prohormone or metabolic activation to reactive intermediate) or by altering endocrine homeostasis (eg, increased steroid clearance). Selected examples of compounds demonstrating reproductive toxicity by one or more of these mechanisms are tabulated and an extensive bibliography of reproductive toxins is attached.

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Factors Determining the Teratogenicity of Drugs

Cited by 13 publications

References 45 publications

Drug‐metabolizing Enzymes in the Placenta and Foetus of Camel and Sheep

Drug‐metabolizing Enzymes in the Placenta and Foetus of Camel and Sheep

Biological markers of male reproductive toxicology.

The Mechanisms of Action of Reproductive Toxins

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