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  • ThesisItemOpen Access
    IN VIVO AND EX VIVO STUDIES ON ANTISPASMODIC EFFECT OF QUERCETIN ON AIRWAY SMOOTH MUSCLE OF NORMAL AND OVALBUMIN INDUCED ASTHMATIC RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2012-11) VAMSI KRISHNA, B; SRINIVASA RAO, G (Major); BHARAVI, K; SRINIVASA PRASAD, CH; ANAND KUMAR, P; ANAND KUMAR, P V S
    ABSTRACT : Asthma is a chronic disease characterized by exaggerated airway smooth muscle contraction to various stimuli and manifested by symptoms viz. recurrent episodes of wheezing, breathlessness, chest tightness and coughing. Quercetin is a polyphenolic flavonoid substance present abundantly in red onions, apples, red wine and tea leaves with anti-inflammatory, anti-allergenic, and antioxidant properties. The present study was carried out to explore anti spasmodic effect of quercetin on rat tracheal smooth muscle in normal and ovalbumin sensitized rats. The study was conducted in four groups of wistar albino rats. Group I consisted apparently normal rats where as rats that are apparently normal in group II received quercetin (20 mg/kg, P.O) for 14 days. In group III rats were sensitized with ovalbumin for experimental induction of allergy and asthma. Where as in group IV rats were sensitized with ovalbumin and also received quercetin (P.O) for 14 days. Rats were sacrificed and tracheal rings were isolated for functional studies using polygraph. Both lungs and tracheal rings were collected and subjected to histological studies. Airway hyper responsiveness in ovalbumin sensitized rats was manifested by decreased EC50 value (4.57 х 10-8M) of carbachol cumulative dose contractile response compared to normal group (1.58 х 10-7M). The mean EC50 value for cumulative dose contractile response of carbachol on tracheal smooth muscle obtained from ovalbumin sensitized with simultaneously quercetin treated rats (1.9 х 10-7M) is significantly higher than ovalbumin sensitized group (4.57 х 10-8M) and almost similar to normal (1.58 х 10-7M) group. This showed the potent antagonizing effect of quercetin against airway hyperresponsiveness in asthmatic condition. Quercetin relaxed the tracheal smooth muscle of normal (IC50: 5.62 х 10-7M) and ovalbumin sensitized rats (1.99 х 10-7M) that were pre contracted with carbachol. Quercetin feeding in ovalbumin sensitized rats decreased the IC50 of quercetin on carbachol induced contraction than normal. Alterations in histological architecture of trachea and lung were observed in ovallbumin sensitized rats. In group IV that received quercetin along with ovalbumin sensitization the histological changes are minimized and protective lesions for epithelium were pronounced. It was apparent from the study that quercetin has antispasmodic effect on airway smooth muscle in normal and ovalbumin induced asthmatic rats and gives protection from allergic inflammatory conditions like asthma.
  • ThesisItemOpen Access
    EVALUATION OF AZADIRACHTA INDICA A. JUSS IN COMBINATION WITH SPIRULINA AS AN ALTERNATIVE TO ANTIBACTERIAL GROWTH PROMOTER IN BROILER PRODUCTION
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2012-11) RAVI, K; BHARAVI, K (Major); RAVI KUMAR, P; ESHWARA RAO, B; NARENDRANATH, D
    ABSTRACT: The use of antibiotic growth promoters in poultry industry is under serious criticism by policy-makers and consumers because of the development of microbial resistance to these products and the potential harmful effects on human health. Hence, there is a trend towards using alternative growth promoters in poultry feeds, particularly natural herbs. In the present study, the performance of broilers fed with diet containing neem, spirulina and their combination was tested. Day old broiler chicks were randomly assigned to six groups each group consisting of 15 chicks. The experiment lasted for 6 weeks and the treatment of various groups consisted of basal diet (group I), 0.05% oxytetracycline (group II), 0.2% neem (group III), 0.2% neem and 1% spirulina (group IV), 0.05% oxytetracycline and 1% spirulina (group V) and 1% spirulina (group VI). All the birds were assessed for growth performance, antioxidant status, liver and kidney function and carcass quality. In vitro analysis showed that the neem leaf extract and twig extract possesses antibacterial property against Escherisia coli and Staphylococcus aureus. The performance of birds fed on antibiotic plus spirulina was found to be the best. Neem, spirulina and their combination could not outperform compared to using antibiotic as feed additive. However, use of neem, spirulina or their combinations could perform well compared to the control group. The physicochemical properties of the meat also followed same trend. Neem and spirulina did not effect the functioning of liver and kidney as was indicated by unaffected serum biochemical profiles and histological architecture. Neem, spirulina and their combinations were found to show cholesterol lowering capacity when compared to antibiotics group or control group. The study concludes that neem and spirulina or their combinations can be used as an alternative to antibiotics as feed additive.
  • ThesisItemOpen Access
    ROLE OF INFLAMMATION AND CURCUMIN ON PHARMACOKINETICS OF PHENACETIN, A CYP1A2 SUBSTRATE IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2012-10) GANGADHARA. N. V. PRASAD, V; SRINIVASA RAO, G (Major); RAVI KUMAR, P; SRINIVASA PRASAD, CH; ANAND KUMAR, P
    ABSTRACT: Role of inflammation and curcumin on the activity of CYP1A2 (a cytochrome P 450 isozyme) were investigated in the present study by determining alterations in the pharmacokinetics of phenacetin and formation of metabolite paracetamol in wistar albino rats, weighing about 200-250g that were randomly divided into four groups consisting six in each group. Rats in group I (control) received phenacetin alone (150 mg.kg-1, PO). Group II received phenacetin 12 h after induction of inflammation using turpentine oil (0.4 mL, i.m). Group III received curcumin (400 mg.kg-1, PO) 60 min prior to administration of phenacetin and Group IV received phenacetin after induction of inflammation followed by curcumin pretreatment. Blood samples were collected from retro orbital sinus at predetermined time intervals prior to and at 0.166, 0.33, 0.67, 1.5, 2, 4, 8 and 12 h after administration of phenacetin. Plasma was separated and stored at -200C until analyzed for phenacetin and its metabolite paracetamol by HPLC assay. Based on plasma concentrations, the pharmacokinetic parameters were determined by compartmental methods. Mean Cmax of phenacetin in group I was 38.13 }2.20 μg.mL-1. There was significant decrease in mean Cmax of phenacetin in rats with inflammation (Group II: 19.50 }2.74 μg.mL-1), curcumin pretreated rats (Group III: 22.23 }2.70 μg.mL-1) and rats with inflammation receiving curcumin pretreatment (Group IV: 17.29 }2.62 μg.mL-1). Means of important pharmacokinetic parameters obtained for phenacetin after its oral administration in group I (control) were: elimination rate constant (β) 0.76 }0.2 h-1; elimination half-life (t.β) 1.22 }0.24 h; area under plasma concentration time curve (AUC0-∞) 90.82 }15.79 μg.h.mL-1; area under first moment curve (AUMC0- ∞) 204.98 }66.96 μg.h2.mL-1; volume of distribution at steady state (Vdss) 2.87 }0.37 L.kg-1; total body clearance (ClB) 1.88 }0.27 L.kg-1.h -1; and mean residence time (MRT) 2.00 }0.32 h and, For the metabolite paracetamol, Cmax, AUC0-∞, and t.β were 8.55 }1.64 μg.mL-1, 41.46 }6.36 μg.h.mL-1 and 2.75 }0.76 h respectively. In group II the mean pharmacokinetic parameters for phenacetin in rats with experimentally induced inflammation were : β, 0.38 }0.07 h-1; t.β, 2.23 }0.48 h; AUC0-∞, 59.53 }7.17 μg.h.mL-1; AUMC0-∞, 13207.76 }58.11 μg.h2.mL-1; Vdss, 8.03 }1.26 L.kg-1; ClB, 2.71 }0.33 L.kg-1.h-1; MRT, 3.26 }0.69 h. It was found that there was a significant (p<0.001) increase in the volume of distribution in rats with inflammation. For the metabolite paracetamol, mean Cmax, AUC0-∞, and t.β were 5.74 }0.87 μg.mL-1, 35.72 }9.61 μg.h.mL-1 and 4.58 }2.32 h respectively. In group III mean pharmacokinetic parameters for phenacetin in curcumin pretreated rats were: β, 0.79 }0.21 h-1; t.β, 1.45 }0.52 h; AUC0-∞, 52.01 }8.54 μg.h.mL-1; AUMC0-∞, 144.61 }63.84 μg.h2.mL-1; Vdss, 5.37 }1.09 L.kg-1; ClB, 3.35 }0.58 L.kg-1.h -1 ; MRT, 2.30 }0.70 h. and, For the metabolite paracetamol, mean Cmax, AUC0-∞, and t.β were 4.82 }1.00 μg.mL-1, 27.19 }3.05 μg.h.mL-1 and 3.57 }0.62 h respectively. In group IV pharmacokinetic parameters for phenacetin in rats with inflammation followed by curcumin pretreatment were: β, 0.55 }0.08 h-1; t.β, 1.42 }0.21 h; AUC0-∞, 47.57 }10.26 μg.h.mL-1; AUMC0-∞, 119.64 }36.16 μg.h2.mL-1; Vdss, 7.01 }0.73 L.kg-1; ClB, 3.88 }0.74 L.kg-1.h -1; MRT, 2.28 }0.29 h and, For the metabolite paracetamol, Cmax, AUC0-∞, and t.β were 5.39 }0.91 μg.mL-1, 29.84 }8.52 μg.h.mL-1 and 2.56 }1.04 h respectively. A significant (P<0.01) decrease in AUC0-∞, while increase in Vdss and clearance for phenacetin was found in rats with inflammation which received curcumin pretreatment. There were no significant alterations in either plasma concentrations or pharmacokinetic parameters of paracetamol (metabolite of phenacetin) in all the four groups. Thus results of the present study indicated that inflammation increased the rate of absorption with shorter half-life for phenacetin. Either inflammation or curcumin pretreatment or both have no role on the activity of CYP1A2 in rats which was indicated by unaltered paracetamol (metabolite) concentrations and pharmacokinetic parameters among all the four groups.