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Protective action of ascorbic acid against mutagenicity of aminopyrine plus nitrite
Abstract:
Mutagenicity of aminopyrine and of aminopyrine plus nitrite was tested by the micronucleus test in bone marrow of mice and by host mediated mutagenicity assay with mice as host animals and S. typhimurium strain G 46. In parallel the possibility of the protective action of ascorbic acid was studied. Aminopyrine at the dose of 90 mg/kg po when administered to mice together with potassium nitrite induced a significant increase in the frequency of micronuclei in polychromatic erythrocytes and proved to be mutagenic for a Salmonella strain. In both systems mutagenicity of the combination of aminopyrine at this dose plus nitrite was abolished completely by ascorbic acid (373 or 622 mg/kg po). Ascorbic acid neither induced a significant increase in the frequency of micronuclei nor was mutagenic for the strain G 46. A formulation of aminopyrine with ascorbic acid is proposed.
Insights
Aminopyrine combined with nitrite is mutagenic, increasing micronuclei frequency and Salmonella mutations. Ascorbic acid completely prevented these mutagenic effects, suggesting a protective role.
Area of Science:
- Toxicology
- Pharmacology
- Genetics
Background:
- Aminopyrine is a common analgesic.
- Nitrite can be present in food and water.
- Investigating potential mutagenicity of drug-nutrient interactions is crucial.
Purpose of the Study:
- To assess the mutagenicity of aminopyrine and its combination with nitrite.
- To evaluate the protective effect of ascorbic acid against potential mutagenicity.
Main Methods:
- Micronucleus test in mouse bone marrow.
- Host-mediated mutagenicity assay using S. typhimurium G 46.
- Administration of aminopyrine, nitrite, and ascorbic acid to mice.
Main Results:
- Aminopyrine (90 mg/kg) plus nitrite significantly increased micronuclei frequency.
- The combination also proved mutagenic to Salmonella typhimurium G 46.
- Ascorbic acid (373 or 622 mg/kg) completely abolished the mutagenicity of aminopyrine plus nitrite.
- Ascorbic acid alone showed no mutagenic activity or increase in micronuclei.
Conclusions:
- Aminopyrine and nitrite together exhibit mutagenic properties.
- Ascorbic acid effectively protects against the combined mutagenicity of aminopyrine and nitrite.
- A formulation of aminopyrine with ascorbic acid is proposed to mitigate risks.