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Genome damage caused by 5-nitrofurantoin in suckling and adult mice detected by micrnoucleus assay

Antibiotic 5-nitrofurantoin has widely been used in paediatric patientsto treat urosepsis for the last 20 years. Recent papers suggest the need for re-evaluation of its safety due to its potential genotoxic effects. Taking into account possible differences in its metabolism and clearance bwteen suckling and adult animals, we conducted a genotoxicological study to reveal possible age-related genome damage caused by this substance. In vivo micronucleus assay (MN) was peroformed on 3 and 8 week old mice. Each group included 5 males and 5 females. Single doses of 5, 10 and 50 mg/kg of 5 nitrofurantoin were injected intraperitonealy. Blood samples from tail vein were taken before injection and 48h, 96h, 168h and 2 weeks after the application. In each animal 1000 reticulocytes were analysed. 5-nitrofurantoin caused a significant increase in MN frequency in both suckling ( mean group value 5, 5%) and adult animals (mean group value 3, 5%) than in control animals. Mean MN frequency in suckling animals was higher than in adult animals for each dose and samoling time. Micronucleus frequency remained significantly higher in suckling animalseven two weeks after exposure to 5-nitrofurantoin. Our study confirmed the genotoxic potency of 5- nitrofurantoin in suckling and adult animals. We proved higher sensitivity of suckling animals to this compound and a signiifcantly longer effect than in adults. This effect is probably due to underdeveloped mechanisms of detoxicification and renal elimination of xenobiotics. Our study confirmed the need for further analysis of this compound and its cost-benefit ratio.

genome damage; micronucleus; development; 5-nitrofurantoin

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