Browsing by Author "BHARAVI, K"
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ThesisItem Open Access CLINICO -DIAGNOSTIC AND THERAPEUTIC STUDIES ON MICROFILARIOSIS IN BUFFALOES IN CERTAIN PARTS OF COASTAL ANDHRA PRADESH(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2017-09) VENKATA KAMESWARA RAO, YANAMADNI; SHOBHAMANI, B(MAJOR); VAIKUNTA RAO, v; BHARAVI, KABSTRACT: To study the occurrence of bubaline microfilariosis, a total of 822 buffaloes from costal Andhra Pradesh were screened during the period from November 2015 to October 2016. Among them 44 buffaloes were found to have microfilariae in the blood. The overall occurrence of bubaline microfilariosis was 5.35 per cent. The occurrence in Veterinary Hospital, in individual holdings and in organized farms was 12.5 percent (23/184), 3.49 per cent (14/401) and 2.95 per cent (7/237) respectively. The occurrence rate was high in 6 to 12 years old buffaloes. Microfilariae were not detected in below one year old buffalo calves. The lactating buffaloes found to be highly (7.93%) susceptible compared to non-lactating buffaloes (3.5%). Similarly, 5.54 per cent murrah buffaloes and 3.07 per cent non-descript buffaloes had microfilariae in the blood. Microfilariosis was recorded through-out the year i.e. during winter (5.21%) summer (4.54%) and monsoon (5.76%) seasons. The microfilaraemic buffaloes exhibited the signs of pyrexia (1030F), anorexia, reduced viii milk yield, reduced rumen motility, epiphora, congested conjunctiva, sunken eyes, edema of dependent parts and dehydration. In chronic cases clinical signs such as pale conjunctivae/Pale oral mucosa, rough/dry skin, uncoordinated movement, loss of vision, debility and mortality in one buffalo, were observed. The hematological alterations recorded in microfilaremic buffaloes were decreased VPRC (27.66+0.66%), Hb (8.75+0.52%), TEC (4.89±0.58×103/μl) and relative eosinophilia (5±0.51). The serum biochemical parameters of microfilaremic buffaloes revealed decreased glucose (31.21±1.55 mg/dl), Total serum proteins (6.21±0.03), and albumin (3.17±0.05g/dl) content. Similarly the serum calcium level (9.43±0.30 mg/dl) and zinc value (56.16±3.73μg/dl) of microfilaremic buffaloes was reduced. To evaluate the therapeutic efficacy, 12 microfilaremic buffaloes were randomly divided into 2 groups. The microfilaremic buffaloes in Group-II were treated with injection doramectin@ 200 μg/kg/sc along with Calup gel @ 300g/animal/day, three doses on alternative days. The buffaloes in Group-III were administered with injection ivermectin @ 200μg/kg/ sc along with oral calcium. The clinical recovery and restoration of physiological status was faster in Doramectin treated group (minimum of 2 days) compared to ivermectin treated group (minimum of 3 days). The magnitude of improvement and reversal to normalcy haemato-biochemical and serum mineral content was far greater after treatment with doramectin. Recurrence of microfilariosis up to 30 days was not recorded in both the groups. It is therefore, concluded that both ivermectin and doramectin were efficient in eliminating microfilariae, however the clinical recovery was much faster in doramectin treated group.ThesisItem Open 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 SABSTRACT : 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.ThesisItem Open Access INFLUENCE OF SODIUM HYPOCHLORITE ON PHARMACOKINETICS OF ENROFLOXACIN IN BROILER CHICKEN(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA, 2019-11) CHELSIA, YATHATI; RAVI KUMAR, P (MAJOR); BHARAVI, K; RAMA DEVI, VAn experimental study was conducted on broiler chicken weighing around 2 kg to know the influence of sodium hypochlorite in drinking water on the oral pharmacokinetics of enrofloxacin. The birds were divided into three groups with eight birds in each. Group I birds that were on normal drinking water received enrofloxacin orally at the dose of 10 mg/kg body weight. Group II birds received sodium hypochlorite in drinking water (10 ml/100L) for seven days followed by enrofloxacin orally (10 mg/kg) on the seventh day. Group III birds also received sodium hypochlorite for seven days but enrofloxacin was given orally (10 mg/kg) 12 hours post withdrawal of sodium hypochlorite containing water. Blood samples from all the treated groups were collected from either left or right tarsal veins at 0 (blank), 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 and 48 h post enrofloxacin dosing and plasma was separated and analyzed by HPLC method. It was observed that t1/2 and tmax did not differ significantly (p<0.05) in all the three groups under study. Elimination rate constant, β was observed significantly (p<0.05) increased in Group III (0.077±0.005 l/h) and Group II (0.071±0.009 l/h) birds compared to that in Group I (0.040±0.002 l/h) birds. There was a noticeable decline in Cmax of enrofloxacin in Group II (1.793±0.160 μg/ml) and Group III (1.958±0.147μg/ml) birds over Group I (2.153±0.245 μg/ml) birds, although not statistically significant (p<0.05). The AUC0-t was apparently decreased though statistically not significant (p<0.05) in both Groups II (31.587±4.241 μg/ml.h) and Group III (33.669±3.593 μg/ml.h) birds. AUC0-α recorded in Group II (32.978±4.087 μg/ml.h) birds was significantly (p<0.05) low when compared to that in Group I (50.648±6.111 μg/ml.h) birds. Thus, the influence of sodium hypochlorite exposure on total exposure to enrofloxacin across time is evident. Likewise, administration of enrofloxacin, 12 hours post withdrawal of sodium hypochlorite (Group III) also resulted in reduced AUC0-α (34.751±3.681 μg/ml.h) of enrofloxacin, though statistically not significant (p<0.05). The area under first moment curve (AUMC) and mean residence time (MRT) recorded in Group III (525.468±61.695 μg/ml.h2 and 15.088±0.431 h) and Group II (538.396±61.064 μg/ml.h2 and 16.484±0.748 h) birds were significantly (p<0.05) lower than those recorded in Group I (1407.185±216.254 μg/ml.h2 and 27.076±1.375 h) birds. Sodium hypochlorite exposure or its exposure till 12 hours before the administration of enrofloxacin could not retain the enrofloxacin molecules for a period similar to that observed in control Group I. Although there was no influence of sodium hypochlorite on the volume of distribution (Vd/F), the total body clearance of enrofloxacin observed in Group III (0.310±0.032 l/kg/h) and Group II (0.329±0.031 l/kg/h) birds was significantly (p<0.05) higher when compared to that in Group I (0.216±0.022 l/kg/h) birds. It can be attributable to altered environment in the renal mechanisms involved in elimination of enrofloxacin or it metabolite(s). The study revealed that, sodium hypochlorite administration altered the pharmacokinetics of the enrofloxacin and the effect of sodium hypochlorite persisted even after its withdrawal 12 hours before the administration of enrofloxacin.ThesisItem Open Access INTERACTION STUDIES ON GYMNEMA SYLVESTRE WITH GLIMEPIRIDE AND INSULIN IN EXPERIMENTAL DIABETES MELLITUS IN RATS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2013-12) Srikanth, M.K; GOPALA REDDY, A(MAJOR); BHARAVI, K; MADHAVA RAO, T; KONDAL REDDY, K; ANAND KUMAR, AABSTRACT: An experimental study was conducted to evaluate the interaction of Gymnema sylvestre extract with insulin and glimepiride in diabetic Sprague dawley rats. Rats were randomly divided into 7 groups of 6 rats in each and blood glucose was estimated to ascertain group differences, if any. Group 1 was kept as normal control. Remaining 6 groups were induced diabetes by intraperitoneal injection of streptozotocin @ 40 mg/kg body weight. After 72 h, rats with blood glucose value of >200 mg/dl were included in the study (n=6). Treatment protocols were initiated 48 hrs post-confirmation of diabetes and continued for 2 months. Group 1: non-diabetic control, group 2: streptozotocin (40 mg/Kg i/p single dose)-induced diabetic (DM) control, group 3: Insulin treatment (4 U/kg b. wt. subcutaneously once daily), group 4: glimepiride treatment (4 mg/kg b. wt. orally once daily), group 5: Gymnema sylvestre methanolic leaf extract treatment ( 400 mg/kg b.wt. orally once daily), group 6: Insulin + Gymnema sylvestre methanolic leaf extract treatment (once daily) and group 7: glimepiride + Gymnema sylvestre methanolic leaf extract treatment (once daily). Blood glucose, body weights, sero-biochemical parameters, antioxidant profile in liver, kidney, brain and testis, ATPases, glucose 6 phosphate dehydrogenase (G6PD), cytochrome P450 (CYP450) activity and glycogen in liver, electron microscopy and histopathology of various tissues were studied at different time intervals. Also, pharmacokinetic interaction of glimepiride with Gymnema sylvestre extract was assessed. There were significant alterations in blood glucose, body weights and other biochemical parameters in diabetic control group 2 as compared to group 1. All the treated groups revealed significant improvement in all the parameters as compared to group 2, while the combination treatment in groups 6 and 7 was found better as compared to single agent-treated groups 3, 4 and 5. The histological studies revealed marked changes in group 2 in all the organs studied, while groups 3 to 5 revealed moderate changes and groups 6 and 7 revealed either minor changes or no pathologically significant changes. Group 1 was devoid of any histological alterations. The electron microscopy of kidney, pancreas and aorta revealed marked alterations in group 2, while groups 6 and 7 revealed better architecture. The pharmacokinetic study revealed the values of T1/2 (h), Ka (h-1), Ke (h-1) and Tmax (h) of glimepiride were siginificantly varied in Gymnema sylevestre pre-treated rats compared to normal rats administered with glimperide In conclusion, the study revealed that addition of Gymnema sylvestre leaf extract to insulin and glimepiride had positive pharmacodynamic interaction in improving the patho-biochemical alterations due to streptozotocin-induced diabetes mellitus in rats, which was evident from greater improvement in sero-biochemical and organ parameters in the groups that were treated using a combination of Gymnema sylvestre with either insulin or glimepiride as compared to individual agent-treated groups. Important pharmacokinetic parameters did not vary significantly when glimepiride was used in combination with Gymnema sylvestre leaf extract.ThesisItem Open Access PHARMACODYNAMIC AND PHARMACOKINETIC EVALUATION OF VERBENONE IN NORMAL AND OVALBUMIN INDUCED ASTHMATIC RATS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2017-05) SURESH, N NAIR; SRINIVASA RAO, G(MAJOR); BHARAVI, K; SATHEESH, K; VINOO, RABSTRACT: Verbenone is a naturally occurring anti-aggregation pheromone generated by bark beetles from a host tree resin precursor, -pinene. Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyper-responsiveness, and an underlying inflammation. In the current study, the acute toxicity at the rate of 2000 mg/kg body weight single oral dosing, sub acute toxicity at the rate of 200 mg/kg oral dosing for 30days, pharmacokinetics of verbenone in normal healthy as well as ovalbumin-induced asthmatic animals and pharmacodynamic activity of verbenone in healthy and asthmatic animals were done. It was found that the verbenone did not produce any toxicity at the dose rate of 2000 mg/kg single oral dose making it a practically non toxic compound. Besides, repeated dose administration for 30 days at the dose rate of 200 mg/kg orally also did not produce any appreciable toxicity. It was also found that the drug did not produce any central nervous system effects as evidenced by lack of variation in spontaneous locomotor activity. In single dose non-compartmental pharmacokinetics in rats, it was found that the mean terminal elimination rate constant was 0.133±0.030/ h, mean elimination t1/2 of 4.368±0.888 hours, observed mean AUC0-inf was 1.361 ± 0.0520 μg/ml*h, observed AUMC0- inf was 6.441± 0.6356 μg/ml*h2, mean residence time was 6.304± 0.385 hours, Cmax and Tmax were 0.497±0.049 μg/ml and h hour, respectively. Apparent volume of distribution during terminal phase was 1134.798± 161.65 (mg)/(μg/ml) and apparent total body clearance of the drug from plasma was 147.1769±5.645 (mg)/(μg/ml)/h. Comparing the pharmacokinetics in normal and asthmatic animals it was found that though the Tmax did not change in disease condition all other parameters were significantly altered. In asthmatic animals maximum plasma concentration changed from 0.497 ± 0.049 to 0.322 ± 0.015 μg/ml. The AUC0-inf had reduced from 1.361 ± 0.052 to 0.828 ± 0.012 μg/ml*h. The observed AUMC 0-inf reduced from 6.441 ± 0.636 to 2.5 ± 0.104 μg/ml*h2. The mean residence time reduced from 6.3036± 0.385h to 3.101± 0.11h and t1/2 had reduced from 4.368 ± 0.888 to 2.149 ± 0.109 hours in asthmatic animals. This experiment indicated that the elimination of verbenone from plasma was faster in asthma and as a result more frequent administration will be required in asthmatic condition. The major pharmacodynamic activities assessed were modulatory activity in contractile response of spasmogens like acetylcholine, histamine and 5-HT in isolated rat tracheal chains from normal, verbenone alone given rats, ovalbumin treated asthmatic rats, dexamethasone treated asthmatic rats and verbenone- treated asthmatic rat. It was found that verbenone reduced the airway yperresponsiveness to the spasmogens in asthma as indicated by the respective EC50’s. The EC50 value of acetylcholine in control animals was 6.17 X 10- 7M whereas the EC50 of verbenone pre incubated group was 7.24 X 10-7 M. In case of verbenone treated control animals, mean EC50 of 7.24 X 10-7 M while the ovalbumin treated asthmatic model showed a significant reduction in EC50 of acetylcholine with a mean of 1.10 X 10-7M. In dexamethasone (5mg/kg) and the test group with verbenone (200 mg/kg) concomitantly with ovalbumin, EC50 of 6.76 X 10-7M and 7.24 X 10-7M were observed. Histamine failed to produce a consistent bronchospasm in rat trachea. The EC50 values of 5- HT in control animals was 2.88 X10-7 M while that of verbenone pre-incubated group was 8.51X10-7 M which was significantly less than control animals. In case of verbenone treated control animals, mean EC50 of 8.51X10-7 M; the effect being significantly less than that of ovalbumin as well as control animals. The ovalbumin treated asthmatic model showed a significant reduction in EC50 of 5-HT with a mean of 1.07 X10-7 M and a range from 8.61 X10-8M to 1.33 X10-7M. The two treatment groups of induced asthma with ovalbumin, namely the standard treatment group which were given dexamethasone (5mg/kg) and the test group with verbenone (200 mg/kg) concomitantly with ovalbumin, showed significant change from ovalbumin alone treated asthmatic animals. The efficacy was comparable with control group, indicating the efficacy of the drugs in alleviating asthma. This was indicated by the mean EC50 of 3.89 X10-7M in case of concomitant dexamethasone and ovalbumin treated animals while in case of verbenone-treated asthmatic animals a mean EC50 of 4.47 X10-7M was noted, which was significantly less than ovalbumin group and even the control group. Though verbenone was able to relieve the airway hyperresponsiveness in asthmatic animals akin to dexamethasone, it failed to produce any direct relaxant effect on precontracted trachea, indicating its inability to act through any bronchodilatory receptors or ion channels. But a non quantifiable relaxation was noted with histamine receptor, indicating the probability of acting on histamine receptors. This finding was supported by histopathology of lung and trachea wherein the verbenone administration reduced the inflammatory status of these organs to near normal stage. Also it was noted that the drug improved the antioxidant status of vital organs like liver, kidney, lung, heart and plasma in asthmatic animals, restoring it to the normal status. Even in disease condition, administration of verbenone did not alter the structural and functional status of the organs grossly as indicated by the normal relative organ weights of the vital organs. Besides, it was found that verbenone possesses significant anti inflammatory activity as assessed by carrageenan induced paw oedema and wound healing activity as evidenced by improved excisional wound healing. But it was found to lack any central analgesic activity. From this it can be concluded that the verbenone is practically non toxic compound which is having a better pharmacokinetic profile so as to enable its use as a drug and exerts anti-asthmatic activity by virtue of its anti inflammatory and anti oxidant activity, though its effect on bronchodilatory mechanisms are not predominant.ThesisItem Open Access PHARMACODYNAMIC AND PHARMACOKINETIC EVALUATION OF VERBENONE IN NORMAL AND OVALBUMIN INDUCED ASTHMATIC RATS.(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2017-05) SURESH N NAIR; SRINIVASA RAO, G (Major); BHARAVI, K; SATHEESH, K; VINOO, RABSTRACT: Verbenone is a naturally occurring anti-aggregation pheromone generated by bark beetles from a host tree resin precursor, -pinene. Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyper-responsiveness, and an underlying inflammation. In the current study, the acute toxicity at the rate of 2000 mg/kg body weight single oral dosing, sub acute toxicity at the rate of 200 mg/kg oral dosing for 30days, pharmacokinetics of verbenone in normal healthy as well as ovalbumin-induced asthmatic animals and pharmacodynamic activity of verbenone in healthy and asthmatic animals were done. It was found that the verbenone did not produce any toxicity at the dose rate of 2000 mg/kg single oral dose making it a practically non toxic compound. Besides, repeated dose administration for 30 days at the dose rate of 200 mg/kg orally also did not produce any appreciable toxicity. It was also found that the drug did not produce any central nervous system effects as evidenced by lack of variation in spontaneous locomotor activity. In single dose non-compartmental pharmacokinetics in rats, it was found that the mean terminal elimination rate constant was 0.133±0.030/ h, mean elimination t1/2 of 4.368±0.888 hours, observed mean AUC0-inf was 1.361 ± 0.0520 μg/ml*h, observed AUMC0- inf was 6.441± 0.6356 μg/ml*h2, mean residence time was 6.304± 0.385 hours, Cmax and Tmax were 0.497±0.049 μg/ml and h hour, respectively. Apparent volume of distribution during terminal phase was 1134.798± 161.65 (mg)/(μg/ml) and apparent total body clearance of the drug from plasma was 147.1769±5.645 (mg)/(μg/ml)/h. Comparing the pharmacokinetics in normal and asthmatic animals it was found that though the Tmax did not change in disease condition all other parameters were significantly altered. In asthmatic animals maximum plasma concentration changed from 0.497 ± 0.049 to 0.322 ± 0.015 μg/ml. The AUC0-inf had reduced from 1.361 ± 0.052 to 0.828 ± 0.012 μg/ml*h. The observed AUMC 0-inf reduced from 6.441 ± 0.636 to 2.5 ± 0.104 μg/ml*h2. The mean residence time reduced from 6.3036± 0.385h to 3.101± 0.11h and t1/2 had reduced from 4.368 ± 0.888 to 2.149 ± 0.109 hours in asthmatic animals. This experiment indicated that the elimination of verbenone from plasma was faster in asthma and as a result more frequent administration will be required in asthmatic condition. The major pharmacodynamic activities assessed were modulatory activity in contractile response of spasmogens like acetylcholine, histamine and 5-HT in isolated rat tracheal chains from normal, verbenone alone given rats, ovalbumin treated asthmatic rats, dexamethasone treated asthmatic rats and verbenone- treated asthmatic rat. It was found that verbenone reduced the airway hyperresponsiveness to the spasmogens in asthma as indicated by the respective EC50’s. The EC50 value of acetylcholine in control animals was 6.17 X 10- 7M whereas the EC50 of verbenone pre incubated group was 7.24 X 10-7 M. In case of verbenone treated control animals, mean EC50 of 7.24 X 10-7 M while the ovalbumin treated asthmatic model showed a significant reduction in EC50 of acetylcholine with a mean of 1.10 X 10-7M. In dexamethasone (5mg/kg) and the test group with verbenone (200 mg/kg) concomitantly with ovalbumin, EC50 of 6.76 X 10-7M and 7.24 X 10-7M were observed. Histamine failed to produce a consistent bronchospasm in rat trachea. The EC50 values of 5- HT in control animals was 2.88 X10-7 M while that of verbenone pre-incubated group was 8.51X10-7 M which was significantly less than control animals. In case of verbenone treated control animals, mean EC50 of 8.51X10-7 M; the effect being significantly less than that of ovalbumin as well as control animals. The ovalbumin treated asthmatic model showed a significant reduction in EC50 of 5-HT with a mean of 1.07 X10-7 M and a range from 8.61 X10-8M to 1.33 X10-7M. The two treatment groups of induced asthma with ovalbumin, namely the standard treatment group which were given dexamethasone (5mg/kg) and the test group with verbenone (200 mg/kg) concomitantly with ovalbumin, showed significant change from ovalbumin alone treated asthmatic animals. The efficacy was comparable with control group, indicating the efficacy of the drugs in alleviating asthma. This was indicated by the mean EC50 of 3.89 X10-7M in case of concomitant dexamethasone and ovalbumin treated animals while in case of verbenone-treated asthmatic animals a mean EC50 of 4.47 X10-7M was noted, which was significantly less than ovalbumin group and even the control group. Though verbenone was able to relieve the airway hyperresponsiveness in asthmatic animals akin to dexamethasone, it failed to produce any direct relaxant effect on precontracted trachea, indicating its inability to act through any bronchodilatory receptors or ion channels. But a non quantifiable relaxation was noted with histamine receptor, indicating the probability of acting on histamine receptors. This finding was supported by histopathology of lung and trachea wherein the verbenone administration reduced the inflammatory status of these organs to near normal stage. Also it was noted that the drug improved the antioxidant status of vital organs like liver, kidney, lung, heart and plasma in asthmatic animals, restoring it to the normal status. Even in disease condition, administration of verbenone did not alter the structural and functional status of the organs grossly as indicated by the normal relative organ weights of the vital organs. Besides, it was found that verbenone possesses significant anti inflammatory activity as assessed by carrageenan induced paw oedema and wound healing activity as evidenced by improved excisional wound healing. But it was found to lack any central analgesic activity. From this it can be concluded that the verbenone is practically non toxic compound which is having a better pharmacokinetic profile so as to enable its use as a drug and exerts anti-asthmatic activity by virtue of its anti inflammatory and anti oxidant activity, though its effect on bronchodilatory mechanisms are not predominantThesisItem Open Access STUDIES ON THE EFFECT OF MORIN, A CYP 2C9 AND CYP3A4 INHIBITING FLAVONOID ON THE PHARMACOKINETICS OF MELOXICAM IN RABBITS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2010-12) SESHAIAH V, PAMULAPATI; SRINIVASA RAO, G (Major); BHARAVI, K; ANAND KUMAR, PABSTARCT: Meloxicam is a novel non-steroidal anti-inflammatory drug with selectivity towards cyclo-oxygenase 2 (COX-2) compared to COX-1. It is extensively metabolized in the liver, primarily by polymorphic cytochrome P450 2C9 (CYP2C9) enzyme, and to a minor extent by CYP3A4 enzyme, to four pharmacologically inactive metabolites and only negligible amounts of the parent drug are found in urine and feces. The effect of morin, a flavonoid known to be dual inhibitor of CYP2C9 and CYP3A4 on the plasma concentrations and pharmacokinetics of meloxicam was studied in male rabbits in the present study in three phases. In phase I, meloxicam alone was administered orally at a dose rate of 1.5 mg.kg-1 whereas in phase II and III the rabbits were given morin by oral route at 10 and 20 mg.kg-1, respectively 30 min before oral administration of meloxicam (1.5 mg.kg-1). Blood was collected at predetermined time intervals by marginal ear vein into heparinized tubes and plasma was separated immediately after blood collection by centrifugation. Meloxicam concentrations in plasma were determined by a validated HPLC method. Pharmacokinetic parameters were calculated by non compartmental technique. In the control group (phase I) where no pretreatment was carried out before the single oral bolus administration of meloxicam (1.5 mg.kg-1), meloxicam was detectable up to 24 h, with the Cmax (Mean±SE, 1.006±0.19 μg.ml-1) at 5.6±0.97 h. The important pharmacokinetic parameters of meloxicam after single oral bolus administration were : β, 0.086±0.11 h-1; t½β, 8.960±1.63 h; AUC0-∞, 12.256±0.91 μg.h.mL-1 ; AUMC0-∞, 167.923±10 μg.h 2.mL-1; Vdss, 1.85±0.4 L.kg-1; ClB, 0.13±0.01 L.kg-1.h -1; and MRT, 14.14±1.66 h. Morin (10mg.kg-1, PO) was given 30 min before administration of meloxicam (1.5mg.kg-1,PO) as pretreatment to rabbits in phase II. The mean value of Cmax obtained was 0.86±0.06 μg.mL-1, which was not significantly low from the control group (phase I). The important pharmacokinetic parameters of meloxicam obtained were : β, 0.082±0.01 h-1; t½β, 8.87±0.99 h; AUC0-∞, 13.16±0.3 μg.h.mL-1; AUMC0-∞, 188.33±17.51 μg.h 2.mL-1; Vdss, 1.62±0.13 L.kg-1; ClB, 0.11±0.0 L.kg-1.h -1; and MRT, 14.27±1.2 h. Upon morin pretreatment prior to meloxicam administration pharmacokinetic parameters such as AUC0-∞, ClB , t½β, Vdss and MRT did not increase significantly from the control group (phase I). In the phase III Morin was given at the dose rate of (20.mg.kg-1, PO) 30 min before administration meloxicam (1.5mg.kg-1,PO). The mean value of Cmax obtained in this phase was 1.39±0.07 μg.mL-1, which was significantly higher from the control group (phase I). There was a significant increase in plasma concentrations of meloxicam at all time points in phase III rabbits when compared to control group of rabbits in phase I after administration of meloxicam. The important pharmacokinetic parameters of meloxicam were : β, 0.09±0.01 h-1; t½β 8.78±1.17 h; AUC0-∞, 21.88±0.30 μg.h.mL-1; AUMC0-∞, 306.25±32.9 μg.h 2.mL-1; Vdss, 0.95±0.08 L.kg-1; ClB, 0.07±0.0 L.kg-1.h -1and MRT 13.95±1.34 h. Upon morin pretreatment at 20 mg.kg-1 prior to meloxicam administration pharmacokinetic parameters such as AUC0-∞, and ClB, were altered significantly from the control group (phaseI).ThesisItem Open Access STUDIES ON THE EVALUATION OF THE PROTECTIVE EFFCT OF TRIBULUS TERRESTRIS IN CADMIUM INTOXICATED RATS(SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2010-12) DHANA LAKSHMI, G; RAVI KUMAR, P; BHARAVI, K; ANNAPURNA, PABSTRACT : Cadmium is one of the most toxic heavy metal naturally occurring in the environment. Cadmium has a tendency to accumulate in vital organs like liver and kidney for many years. Majority of the deleterious effects of cadmium are related to its potential to induce oxidative damage within the cells. Thus supplementation of antioxidants during cadmium intoxication would have beneficial effect. Tribulus terrestris (TT), a flowering plant belong to the family Zygophyllaceae, and widely prevalent locally is reported to have antioxidant properties. Hence, the protective effect of ethanolic extract of whole plant of TT was assessed in cadmium intoxicated rats. Forty Wistar strain male rats aged about 60 days were randomly assigned to 4 equal groups. Group I was maintained as control, while groups II, III and IV rats received cadmium @3mg/kg body weight s/c once a week for 4 weeks. In addition, group III rats were administered with TT extract @ 5mg/kg body weight per os daily for 6 weeks while group IV rats received vitamin E @ 75mg/kg body weight per os daily for 6 weeks. All the rats were sacrificed at the end of 6th week. Cadmium toxicity in group II rats was manifested as a decrease in body weight gain, decrease in antioxidant markers viz., SOD, GSH and CAT, increase in peroxidation markers viz., TBARS and protein carbonyls, in liver and kidney, decrease in total proteins, albumin and globulin in serum and increase in ALT, BUN and creatinine in serum. Alterations in histological architecture and increased cadmium concentration were also observed in livers and kidneys following cadmium intoxication. In groups III and IV that received TT and vitamin E supplementation along with cadmium, a reversal in the biochemical alterations induced by cadmium was observed. This trend was in agreement with improved body weight gain and less severe histological changes and reduced cadmium load in liver and kidneys. It was apparent from the study that ethanolic extract of TT has protective effect in cadmium induced oxidative damage in liver and kidney tissues.