Residue Profile of Enrofloxacin and its Primary Metabolite Ciprofloxacin in Broiler Chicken
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Date
2012
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Publisher
Tamil Nadu Veterinary and Animal Sciences University
Abstract
An experimental trial was conducted to determine the residueomics of
enrofloxacin and its primary metabolite ciprofloxacin in broiler chicken under
controlled experimental condition, at recommended therapeutic dose of enrofloxacin
@ 10mg Kg-1 in drinking water for five consecutive days (from 43rd to 47th day of
age), till 9th day post treatment. Parameters like Zootechnical performance,
behavioural, haematology, biochemical, immunological, histopathological and
transmission electron microscopic profile were studied as an index of Safety
Pharmacology of enrofloxacin in broiler chicken.
Effects of various cooking process (Boiling, microwaving, roasting and
grilling) on enrofloxacin and its metabolite ciprofloxacin residues in edible tissues of
broiler chicken were also evaluated.
A field study was conducted to assess the prevalence of enrofloxacin and
ciprofloxacin residues in broiler meat and organ samples collected from various retail
outlets in Chennai.
A high performance thin layer chromatography (HPTLC) method was
developed and validated for the simultaneous determination of enrofloxacin and
ciprofloxacin in plasma and edible tissues (muscle, liver, kidney and skin). As a non
invasive technique to monitor drug residues, standardized the HPTLC method for
simultaneous determination of enrofloxacin and ciprofloxacin in feather and
droppings.
In the experimental study, during the post treatment period the tissue : blood
concentration ratio for enrofloxacin and its metabolite ciprofloxacin residues in liver
and kidney was found to be high. The ratio for enrofloxacin on day 1 post treatment in
breast muscle was equal, but in thigh muscle and skin it was below while exceeded
the plasma concentration on day 3 post treatment.
The ciprofloxacin concentrations were always lower than that of the parent
drug enrofloxacin. With the exception of critical metabolic and excretory organs
(liver: 20-70% and kidney: 28-62%), tissue (skin, breast and thigh muscle)
ciprofloxacin never exceeded the 4-6% of the parent drug concentrations.
Ciprofloxacin was found to be rapidly depleted from the chicken body compared to
that of enrofloxacin.
There was a significant difference in total enrofloxacin residues between
breast muscle and thigh muscle at all the time points examined during the withdrawal
period.
The withdrawal period for enrofloxacin and its primary metabolite
ciprofloxacin in broiler chicken was calculated as per EU and Japan MRLs.
Accordingly, it was found to be 5 days and 9 days respectively.
High level of enrofloxacin residues was recorded in feathers, even at
concentrations far higher than those measured in edible tissues. Withdrawal times,
based on the concentrations of enrofloxacin residues in edible chicken meat, were not
adequate to reduce antimicrobial residues in chicken feathers. Enrofloxacin residues
could be detected in droppings even up to 7th day post treatment, thus it warrants
environmental concern.
Enrofloxacin administration decreased the lymphocyte count and humoral
immune response, with associated histopathological changes in spleen and bursa of
Fabricius, however, on 9th day post treatment reversal in the effect was noticed. It did
not have any appreciable effect on Zootechnical performance of the broilers.
A significant elevation in serum gamma glutamyl transferase (GGT) was
observed after the 4th dose of the enrofloxacin and on day 1 post treatment. The
elevated levels were declined gradually during the withdrawal period. The elevated
levels of the GGT were correlated with the histopathological changes of the liver and
further validated by the electron microscopic observations. A significant but transient
increase in serum uric acid and creatinine was noticed after the 4th dose and on day 1
post treatment of enrofloxacin. The elevated levels were declined gradually during the
withdrawal period. These biochemical changes were in congruent to histopathological
alterations in kidneys and further bolstered by the ultra structural changes observed in
kidney.
Histopathological examination of skin revealed hyperkeratosis and thickening
of the epithelial layer, however, lesions were mild and revealed normal epidermis
layer in day 7 and 9 post treatment groups. The histopathological results of feather
follicle showed hyperplasia of squamous epithelial cells and vacuolated epithelial
cells, which were persisted in day 1 and 3 post treatment groups. However,
hyperplasia of follicular epithelium is the only appreciable lesion found to be
persisted till 9th day post treatment.
Fluoroquinolone arthropathy was manifested in juvenile cartilages as
evidenced by histopathological changes in articular and sternal cartilages, and
possible correlation with a significant reduction in antioxidant enzymes (Glutathione
S-transferase, Glutathione and Catalase) in liver, muscle and serum.
Different cooking methods caused perceptible decrease in enrofloxacin residue
levels in all the tissues studied, however, the residue levels remained high in cooked
tissues and found to be far above the MRLs prescribed by EU and Japan. Amongst the
various agents affecting antibiotics residue after the cooking process, it was found that
cooking time and temperature can play crucial roles about antibiotic residue
reduction.
The field study revealed that 30.56% of the samples investigated were found
to contain detectable levels of enrofloxacin residues at the time of marketing. The
incidence of enrofloxacin and ciprofloxacin residues as found in broiler, tissue wise
was as follows: liver>kidney>skin. However, the residues of enrofloxacin were not
detected in any of the breast and thigh muscle samples investigated. Even though the
mean concentrations of enrofloxacin residues were found to be below the MRLs
prescribed by EU and Japan regulations, 4 (18.18%) liver, 3 (16.67%) kidney and 2
(13.33%) skin samples had enrofloxacin residues higher than the Japan MRLs and
found to be violating the regulations. However, all muscle samples investigated were
found to be safe as per EU and Japan MRLs.
Description
Keywords
Ciprofloxacin, HPTLC, Residue profile, Safety pharmacology, Broiler chicken