Agriculture Reference
In-Depth Information
control of the illegal use of these compounds. The EU Commission Decision
2003/181/EC of 13 March, 2003 has established the minimum required
performance limit (MRPL) of 1 µg kg
−1
for each nitrofuran metabolite based
on the high efficiency of LC-MS/MS methodologies for detecting bound
nitrofuran metabolites in edible tissues [8].
Finally, it should also be taken into account that, contrary to the complete
ban of the nitrofuran use in livestock production, these drugs are readily
available for veterinary (except for food producing animals) and human
therapy: nitrofurazone is used for topical application on infected burns and
skin infections [29]. It works by eliminating bacteria or preventing their
growth. Furazolidone is available for the oral treatment of cholera [30],
bacterial diarrhea, and giardiasis [31]; and nitrofurantoin is commonly used to
treat infections of the urinary tract [32].
4.
C
HEMICAL
S
TRUCTURE AND
P
HARMACOLOGY
Nitrofurans are Schiff's base derivatives of nitrofuraldehyde known to
have a broad-spectrum of antimicrobial activity. They are, for the most part,
bacteriostatic, although at high doses they can be bactericidal [10]. These
drugs are most active in acid environments (optimum pH is 5.5), are only
slightly soluble in water and are not effective systemically. They are used
orally, topically and rarely parenterally. Absorption from the gastrointestinal
tract is poor and the drug is eliminated very rapidly [12].
Nitrofurans are characterized by possessing in its chemical structure a
radical nitro (-NO2) in position 5 of the furan ring, hence the designation of 5-
nitrofurans, and in position 2 a different radical depending on the nitrofuran.
A relationship between the chemical structure and antibacterial activity is
not still completely elucidated; however, from a therapeutic point of view it
has been observed that the position of the nitro group is a relevant feature in
the antibacterial activity.
Although their basic mechanism of action remains unclear, nitrofurans
inhibit many microbial enzyme systems, including those involved in
carbohydrate metabolism. The drug is metabolized to nitroreductases that lead
to formation of nitro anion radicals that inhibit genetic translation [13].
It was
proposed a biological action mechanism for these drugs [33] in
which the nitro group reduction produced intermediate species that interact
with DNA by oxidizing it and liberating thymidine phosphate, which causes
damage to DNA by destabilizing the double helix. Moreover, the effect of the
