Chandra, G. SarathHariharan, P.Thejomoorthy, P.Vairamuthu, S.Kumar, V. SureshTANUVAS2016-07-252016-07-252012http://krishikosh.egranth.ac.in/handle/1/69815An 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.enCiprofloxacinHPTLCResidue profileSafety pharmacologyBroiler chickenThesis