Agriculture Reference
In-Depth Information
Mutagenicity studies have been conducted in the 1970s and 1980s,
revealing the potential effects of nitrofurans in bacterial and mammalian cells.
In bacterial systems, nitrofuran derivatives are almost all mutagenic [34]. It
was suggested that endogenous nitro-reductase was accountable for the
in vitro
reduction of nitrofurans in
E.coli
, leading to the formation of cellular DNA
lesions in the stationary phase of bacterial growth [59]. The formation of DNA
adducts after bacterial replication causes the induction of error prone DNA
repair processes, indicating the mutagenic potency of the drug [34].
The toxicity and formation of mutagens in mammalian cells
in vitro
is less
understood. Studies suggested that irreversible damage to the DNA of human
epithelial cells (HEp-2) as well as hormone disturbances (reflecting endocrine
dysfunction) occurred prevalently when cells were exposed to furazolidone
[60-61].
Furthermore, several nitrofuran derivatives are mutagenic in mammalian
cells
in vitro
[34], suggesting that the use of nitrofuran derivatives in medicine
constitutes a potential risk for human health.
The majority of the available information was obtained from
in vivo
studies which utilize mouse and rat models for examination of the effects of
furazolidone and mainly nitrofurazone or its residue semicarbazide [61].
The genotoxic effect of nitrofurans, including furazolidone, has been also
documented [62]. The respective mechanism of action still remains unclear,
and is assumed to be based mainly on the products of the oxido-reductive
metabolism, i.e., formation of incomplete reduction products, peroxyl and
hydroxyl radicals that can induce protein and oligonucleotide.
A major study conducted in 1988 examined groups of F344/N and B6C31
mice (of both sexes) fed nitrofurazone for a period of 14 days, 13 weeks or
two years. Results showed clear evidence of carcinogenic activity as a direct
consequence of nitrofurazone intake. This was demonstrated by an increased
incidence of fibro-adenomas of the mammary gland in female mice, as well as
benign mixed tumors and granulose cell tumors in the ovaries. Other common
signs of toxicity in both species and genders of mice included convulsive
seizures, osteoporosis, degenerative arthropathy and more commonly rough
hair coats and lethargy, as well as a dose related decrease in feed consumption.
In contrast, no significant alterations in tested immunological or host
resistance parameters were shown in B6C3F1 mice administered nitrofurazone
for a consecutive 14 days at various low doses [15].
A further study on nitrofurazone concluded that adverse reproductive
effects in male and female mice resulted from relatively low doses (≥ 100
ppm) of nitrofurazone [63].
