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Inhibition of ATP synthesis associated with 6-aminonicotinamide (6-AN) teratogenesis in rat embryos
Insights
6-aminonicotinamide (6-AN) exposure in pregnant rats caused significant embryo malformations and reduced adenosine triphosphate (ATP) levels. Co-administration of nicotinamide (NAM) protected against these adverse effects, suggesting a link between ATP depletion and 6-AN embryotoxicity.
Area of Science:
- Developmental toxicology
- Biochemistry
- Teratology
Background:
- 6-aminonicotinamide (6-AN) is a known teratogen.
- Adenosine triphosphate (ATP) is crucial for cellular energy and embryonic development.
Purpose of the Study:
- To investigate the relationship between 6-aminonicotinamide (6-AN)-induced embryotoxicity and adenosine triphosphate (ATP) levels in developing rat embryos.
- To evaluate the protective effect of nicotinamide (NAM) against 6-AN teratogenicity and its impact on ATP concentrations.
Main Methods:
- Pregnant rats were administered 6-aminonicotinamide (6-AN) at day 12 of gestation.
- Embryos were collected at various time points post-injection to measure ATP concentrations.
- Nicotinamide (NAM) was administered at different intervals after 6-AN to assess its protective potential.
- Fetal malformations were evaluated in near-term fetuses.
Main Results:
- 6-AN injection significantly reduced embryonic ATP concentrations by approximately 50% within 1-48 hours.
- All fetuses from 6-AN-treated rats exhibited malformations near term.
- Administration of nicotinamide (NAM) 1 hour after 6-AN reduced malformation rates to 15% and minimized ATP depletion.
- Delayed NAM administration (2 and 4 hours) resulted in intermediate ATP levels and malformation frequencies.
Conclusions:
- A strong correlation exists between the embryotoxic effects of 6-AN and its ability to depress embryonic ATP levels.
- Nicotinamide (NAM) demonstrates a protective effect against 6-AN-induced embryotoxicity, likely by mitigating ATP depletion.
- These findings highlight the critical role of cellular energy metabolism in embryonic development and susceptibility to teratogens.
Abstract:
Pregnant rats were injected ip with 6 mg/kg 6-aminonicotinamide (6-AN) at day 12 of gestation. Embryos removed between 1 and 48 h later had reduced adenosine triphosphate (ATP) concentrations, of about 50% of control values. All fetuses examined near term were malformed. Nicotinamide (NAM, 100 mg/kg) given ip 1 h after 6-AN afforded protection: malformations occurred in only 15% of the survivors; and there was minimal ATP reduction, 15% below control values. NAM given 2 and 4 h after 6-AN produced intermediate ATP concentrations and malformation frequencies. Thus, there was a relation between the embryotoxic and ATP-depressant actions of 6-AN in day 12 rat embryos.