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2011 - 20187
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Subject: Veterinary Pharmacology and Toxicology × End date: 2018 × Start date: 2010 × Thesis Type: Ph.D ×
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    ThesisItemOpen Access
    ROLE OF EUGENOL IN REVERSAL OF VASCULAR DYSFUNCTION INDUCED BY EXPERIMENTAL DIABETES AND HYPERTENSION
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA, 2018-10) Vamsikrishna, Bobba; Srinivasa Rao, G(MAJOR); Ravi Kumar, P; Rama Devi, V; Vinoo, R
    ABSTRACT : Phenylpropanoids are a diverse group of phytochemicals with immense health benefits and found throughout the plant kingdom. Eugenol is a member of the phenylpropanoids and is remarkably versatile molecule which is present abundantly in clove, nutmeg, cinnamon, basil and bay leaf. Epidemiological evidence and clinical trial data indicates that due to presence of biologically active phytochemicals, the plant originated diets can reduce the risk of chronic disease conditions such as cardiovascular disease, hypertension, diabetes and cancer. Hypertension and diabetes are the lifestyle diseases which are considered to be main causes of mortality for decades in humans. Vascular dysfunction is the major change that is associated with diabetes and hypertension. It is well documented that both diabetes and hypertension occur together in most of the human beings that is an additive cause for increase in risk of vascular complications. Though there are standard treatments available at present for these complications, a look for an alternative approach that can better address the vascular problems is most wanted. Hence the present study was designed to know the effect of eugenol against vascular dysfunction associated with either diabetes or hypertension alone and diabetes with hypertension together. The study was carried out in rats that are divided into eight groups with ten rats in each. Group-I (normal control) received vehicle alone for eight weeks whereas group II (eugenol control) received eugenol orally and daily at the rate of 80 mg/kg for eight weeks. Group- III, IV and V constitute experimentally induced hypertension control, diabetic control and diabetic rats with hypertension. Hypertension was induced in rats with administration of L-NAME in drinking water (40 mg/kg/day). Whereas single dose of streptozotocin was injected intraperitoneally at 40 mg/kg for inducing diabetes in rats. Group V rats received both streptozotocin and L-NAME. Group- VI (eugenol treated hypertensive rats), VII (eugenol treated diabetic rats) and VIII (eugenol treated diabetic rats with hypertension) received eugenol 80 mg/kg orally from the day after the onset of diabetes, hypertension or both conditions experimentally. Development of hypertension and diabetes in rats was confirmed by decrease in total nitrate/nitrite levels in serum and high blood glucose levels (>300 mg/dl) respectively. At the end of the study, rats were sacrificed and thoracic aorta was collected for studying vascular reactivity and histopathology. In addition, effect of eugenol in ameliorating the oxidative stress induced by experimental diabetes, hypertension and diabetes associated hypertension was also studied. Moreover, liver and kidney function markers in plasma were estimated in different study groups to know the effect of eugenol on liver and kidney function. Total nitrate (NO3-) and nitrite (NO2-) levels in serum were significantly (P < 0.05) decreased in hypertension control, diabetic control and diabetes associated hypertensive rats. Eugenol treatment had no impact on reversing the nitrate and nitrite levels in diabetes and hypertension back to the normal values noticed in control rats. Hyperglycemia was observed both in diabetic and diabetic hypertensive rats. Eugenol treatment did not have any effect in restoring the blood glucose levels to normal. Eugenol treatment could not show any favorable effect on body weight that had reduced in diabetic and diabetic hypertensive rats. Eugenol treatment had no effect on increased oxidative stress noticed in diabetic, hypertensive and diabetic hypertensive rats. Levels of liver function markers were raised in diabetic and diabetic hypertensive rats indicating liver damage and eugenol had no protective effect on liver damage. But elevated plasma creatinine, blood urea nitrogen levels and reduced plasma total protein in diabetic and diabetic hypertensive rats were restored to normal by eugenol treatment indicating protective effect of eugenol on kidney. Vascular reactivity was studied in-vitro by taking myographic recordings of aorta as described here; 1. Contractile response to phenylephrine and 5-HT. 2. Ach relaxation on phenylephrine and 5-HT induced contraction. 3. Eugenol relaxation of phenylephrine and 5-HT induced contraction. The lower mean log EC50 values of phenylephrine (-7.856 M) and 5-HT (-6.967 M) in hypertensive control and diabetic hypertensive rats (Phe: -7.960 M and 5-HT: -7.035 M) demonstrates hyper responsiveness of aortic smooth muscle to phenylephrine and 5-HT in comparison with normal control (Phe: -6.588 M and 5-HT: -5.700 M), and hyper-responsiveness of aorta to phenylephrine was partially reversed by eugenol treatment. But aorta from diabetic control rats showed hyper-responsiveness to phenylephrine (-7.137 M) and hypo reactivity to 5-HT (-5.247 M) compared to normal control rats. Eugenol treatment showed no impact on hyper-reactivity to phenylephrine or hypo-reactivity to 5-HT in diabetic rats. Maximum relaxation (% Emax) by acetylcholine in aorta on phenylephrine and 5-HT induced contractions was significantly reduced in diabetic, hypertensive and diabetic hypertensive rats. The effect was complete in hypertension and diabetic hypertension. Eugenol treatment had no significant change on acetylcholine induced relaxation in diabetic rats but significantly (P<0.001) improved relaxation in hypertensive and diabetic hypertensive rats. Eugenol produced dose dependent relaxation on phenylephrine and 5-HT induced contraction in all experimental groups but its effect was less potent than acetylcholine. Emax of eugenol on phenylephrine induced contraction was reduced in hypertensive, diabetic and diabetic hypertensive rats. Eugenol treatment to diabetic and diabetic hypertensive rats significantly improved Emax of eugenol. Eugenol relaxation on 5-HT induced contraction in diabetic control, hypertensive control and diabetic hypertensive rats were similar to control rats. The pathological changes observed in aorta, heart and kidney due to hypertension, diabetes and diabetic hypertension were not reestablished to normal with eugenol treatment. In conclusion, eugenol partially reversed phenylephrine and 5-HT induced vascular hyper-responsiveness in aorta and augmented the relaxation to acetylcholine in hypertensive and diabetic hypertensive rats but failed to produce a similar response in diabetic rats. However, eugenol had no role in maintaining blood glucose and serum nitrate levels indicating its inability to alleviate diabetes and hypertension. Further, eugenol treatment could not modulate oxidative stress and histopathological changes induced by diabetes and hypertension in plasma, heart and kidney. Further studies are needed to know the molecular mechanism involved in partial reversal of vascular dysfunction by eugenol.
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    ThesisItemOpen Access
    ENDOCRINE DISRUPTING ACTIONS OF CADMIUM AND EXPERIMENTAL EVALUATION OF PROTECTION BY GREEN TEA EXTRACT
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2014-05) SHIVAKUMAR, PABBATHI; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANJANEYULU, Y; RAMANA REDDY, Y; UDAYA KUMAR, M
    ABSTRACT : An experimental study was conducted to evaluate the neuro-endocrine disrupting actions of cadmium and the effect of cadmium on the progeny that were born to cadmium exposed rats and to evaluate the protective role of green tea on neuro-endocrine disrupting actions of cadmium in Sprague dawley rats. Rats were randomly divided into 4 groups of 30 rats in each (male rats =12, female rats=18).Group 1 served as Sham control Group 2 treated with CdCl2, Group 3 treated with Green tea extract treatment and Group 4 Cd + green tea extract treatment. Blood was collected from all the groups at monthly intervals for analyzing sero-biochemistry (blood glucose, total cholesterol, HDL-cholesterol, triglycerides, total protein and albumin, biomarkers of cardiovascular, hepatic and renal pathology, and hormonal profile (thyroid profile, sex hormones). The key enzymes concerned with metabolism were assayed. Immune status was studied at the end of 3rd month by phytohaemagglutinin assay. Rats were subjected to neuro-behavioural studies at the end (Elevated plus maze and Morris water maze). Epididymal sperm count in males and estrous cycle pattern in females were studied. At the end of 3 months, 12 rats (6 males and 6 females) from each group were sacrificed to collect various organs and endocrine glands and subjected them to biochemical, histological and electron microscopic studies. Cadmium concentration was estimated in all the treated groups in kidney, testes, liver and brain at the end of 3 months. In all the groups, twelve (12) females were mated at the end of three months with male rats belonging to respective groups/treatments and the treatment was continued till 17th day of gestation. 50% of the pregnant rats in the respective groups were sacrificed on day 19 to study skeletal and soft tissue developmental anomalies and the rest were allowed to normal delivery. The pups of F1 generation from all the groups were kept till weaning (post-natal day 21) and were subjected to sero biochemical, neurobehavioural studies andthyroid hormone profile were estimated. There were significant alterations in sero-biochemistry biomarkers of cardiovascular, hepatic and renal pathology and hormonal profile thyroid profile, group 2 as compared to group 1.Treatment group revealed significant improvement in all the parameters as compared to group 2, while the combination treatment group 4 was found better The histological studies in group 2 revealed marked changes in all the organs studied, while groups 4 revealed moderate changes and groups 1 and 3 revealed no pathologically significant changes. The electron microscopy of kidney, testis and thyroid revealed marked alterations in architecture in group 2, while groups 4 revealed better architecture. There were no significant alteration in the TEM samples of the offspring and there were no skeletal abnormalities in the offspring as evidenced by skeletal staining. The results of the study revealed neuro-endocrine disrupting actions of cadmium and protctive role of green tea in cadmium toxicity. Further studies are warranted to know in detail on the endocrine disrupting actions of cadmium and protective role of green tea at various concentrations.
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    ThesisItemOpen 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, A
    ABSTRACT: 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.
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    ThesisItemOpen Access
    TOXICODYNAMIC INTERACTION OF LEAD WITH CADMIUM AND THERAPEUTIC EVALUATION OF N-ACETYL L-CYSTEINE IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-07) ANlL KUMAR, B; GOPALA REDDY, A(MAJOR); RAVl KUMAR, P; MADHAVA RAO, T; ANAND KUMAR, A
    ABSTRACT: An experimental study was conducted to evaluate the molecular mechanisms of lead and cadmium toxicity and their toxicodynamic interaction, and to evaluate therapeutic potential of N-Acetyl L-cysteine (NAC) against the toxicity in Wstar rats. After an acclimatization period of 2 weeks, rats were randomly divided into 8 groups comprising of 6 rats in each. Group 1 was kept as normal control throughout the experimental period, 2 was given NAC @ 300 mg per kg body weight administered by oral gavage, 3 was given lead (lead acetate @ I000 ppm in feed), 4 was given cadmium (cadmium chloride @ 300 ppm in feed), 5 was given lead + cadmium as per above doses in feed, 6 was given lead + NAC as per above schedule, 7 was given cadmium + NAC as per above schedule, and group 8 was given lead + cadmium + NAC as per above schedule for 3 months. Body weights, haematology (TEC, TLC, Hb, PCV, MCH and MCHC), activity of 6-ALAD and erythrocytic SOD, sero-biochemical parameters (ALT, CPK, troponins, plasma TBARS and serum creatinine), antioxidant profile (GSH, GST, TBARS and protein carbonyls) in liver, kidney, heart, testis and brain, ATPases and tissue lipids in liver and brain, neurotransmitters (Ach and glutamate) in brain, CYP450, glycogen and G6PD in liver, weight of testes, testicular LDH and sperm count, electron microscopy of kidney in cadmium exposed groups and histopathology of liver, kidney, testis and heart were studied. Also, interaction of lead and cadmium with zinc and copper in liver, kidney, heart, testis and brain was assessed. The present study revealed significant alterations in body weights, haematology, sero-biochemical parameters, antioxidant profile, ATPases, tissue lipid profile, neurotransmitter, CYPd50, glycogen, GGPD, weights of testes, testicular LDH, sperm count, and concentration of zinc and copper in toxic control groups 3, 4 and 5 as compared to control and NAC-treated groups. The toxic combination (Pb + Cd) group 5 showed significant alterations in most of the parameters studied as compared to Pb alone and Cd alone administered groups. All the NAC-treated groups revealed significant improvement in all the parameters. The histological studies of liver, kidney, testis and brain revealed marked changes in toxic control groups, while therapeutic groups revealed mild changes or no pathologically significant changes. Groups 1 and 2 were devoid of any alterations. The electron microscopy of kidney revealed marked alterations in kidney architecture in groups 4 and 5, while groups 7 and 8 revealed better architecture. The results of the investigation revealed that lead, cadmium' and their combination induced toxicity to the biological system due to the excess generation of free radicals and impairment of antioxidant defenses. Toxic effects were more pronounced in the group that received a combination of lead and cadmium suggesting positive toxicodynamic interaction. Use of NAC countered the adverse effects of lead and cadmium induced toxicity to a major extent suggesting its antioxidant potential owing to replenishment of tissue pool of GSH. Further, NAC administration reduced the extent of accumulation of lead and cadmium in various tissues.
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    ThesisItemOpen Access
    INTERACTION OF TRIGONELLA FOENUM GRAECUM WITH INSULIN AND GLIMEPIRIDE IN EXPERIMENTAL DIABETES MELLITUS IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2011-01) HARITHA, C; GOPALA REDDY, A(MAJOR); SRINIVASA RAO, G; ANJANEYULU, Y; MADHAVA RAO, T; RAMANA REDDY, Y
    ABSTRACT: An experimental study was conducted to evaluate the interaction of fenugreek seed powder with insulin and glimepiride in diabetic Sprague dawley rats. Rats were randomly divided into 7 groups of 8 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 >250 mg/dl were included in the study (n=8). Treatment protocols were initiated from day 2 post-confirmation of diabetes and continued for 8 wks. 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 once daily), group 4: glimepiride treatment (4 mg/kg orally once daily), group 5: fenugreek seed powder treatment (1 g/kg orally once daily), group 6: Insulin + fenugreek seed powder treatment (once daily) and group 7: glimepiride + fenugreek seed powder treatment (once daily). Blood glucose, body weights, sero-biochemical parameters, antioxidant profile in liver, kidney, brain and testis, ATPases in liver and brain, relative weights of kidney and testes, electron microscopy of kidney and histopathology of various tissues were studied at different time intervals. Also, pharmacokinetic interaction of glimepiride with fenugreek seed powder 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 groups 6 and 7 were found better as compared to single agent-treated groups 3 through 5. The histological studies revealed marked changes 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 alterations. The electron microscopy of kidney revealed marked alterations in kidney architecture in group 2, while groups 6 and 7 revealed better architecture. Fenugreek seed powder treatment increased AUC and elimination half life of glimepiride in combination as compared to glimepiride-alone treated group, while the Cmax and tmax did not vary between groups 4 and 7. The results of the study revealed positive pharmacodynamic interaction between fenugreek and either insulin or glimepiride in improving the patho-biochemical alterations in diabetic rats. Further, there was a favourable pharmacokinetic interaction. Further studies are warranted to estimate P-gp and OATP activities along with CYP2C9 estimation for better understanding of pharmacokinetic interactions of fenugreek and glimepiride in diabetes mellitus.
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    ThesisItemOpen Access
    ANTICARCINOGENIC ACTIVITY OF CINNAMALDEHYDE AND NANO CINNAMALDEHYDE AGAINST MAMMARY CANCER IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2018-05) Ravi, Killi; Ravi Kumar, P(MAJOR); Bharavi, K; Rama Devi, V; VINOO, R
    ABSTRACT: Cancer is a growing health problem in both developing and developed countries. Cancer chemoprevention is defined as the use of natural or synthetic agents that reverse, suppress or arrest carcinogenic and/or malignant phenotypic progression towards invasive cancer. The effectiveness of many anticancer drugs is limited due to their inability to reach the target site in sufficient concentrations and efficiently exert the pharmacological effect on affected cells without harming the healthy cells. Therefore, the search for new anticancer agents with better efficacy and fewer side effects is an ongoing phenomenon. Plant phenolic compounds are a group of secondary metabolites with wide pharmacological activities (Al-Rimawi et al., 2016). Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of different oxidative associated diseases such as cancer (Dai and Mumper, 2010). trans- Cinnamaldehyde is a phenolic compound found naturally in various species of the genus Cinnamomum and is used in preparing beverages, medicinal products, perfumes and cosmetics. Nanoparticles (NPs) are versatile agents with a variety of biomedical applications including drug delivery. Keeping this in view, the present study was undertaken to evaluate the anticancer potential of cinnamaldehyde (CNMA) and its nano preparation, the nano zinc cinnamaldehyde (CZN) in chemical induced rat breast cancer model. Further, cinnamaldehyde was also studied for its disposition kinetics in rats. For induction of mammary tumors, fifty days old virgin female Sprague-Dawley rats were administered with single oral dose of 20 mg dimethyl benz(a)anthracene (DMBA). Those rats positive for mammary tumors on 90th day were only selected for further studies. The study was carried out in seven experimental groups viz. normal control (C), DMBA control (DMBA-C), cinnamaldehyde prophylactic (CNMA-P), cinnamaldehyde treatment (CNMA-T), nano cinnamaldehyde control (CZN-C), nano cinnamaldehyde treatment (CZN-T) and tamoxifen (TAM). CNMA-P group rats received cinnamaldehyde (50 mg/kg b.wt) orally starting from the 45th day i.e. five days prior to the DMBA administration and continued to received the same until the end of the study on 120th day. CNMA-T, CZN-C and TAM treatment groups received the respective treatments for a period of 30 days beginning from the 90th day. All the animals were sacrificed on 120th day. Plasma concentration of cinnamaldehyde and cinnamic acid were estimated in rats administered with cinnamaldehyde at a dose rate of 500 mg/kg b.wt. From the pharmacokinetic study it was evident that cinnamaldehyde is rapidly converted into cinnamic acid (CA). Apparent volume of distribution (Vd) and plasma clearance (Cl) were high for CNMA but its AUC0-t, MRT and t1/2 values were low when compared to CA. Tumor volume, tumor multiplicity, tumor burden, body weight, tissue antioxidant and peroxidation status and various plasma biochemical parameters including total sialic acid (TSA) levels were assessed in all experimental groups. In addition tumor latency period was recorded in CNMA-P group. Mammary tumor tissues were subjected to light and electron microscopic examination for pathological changes and immunohistological studies for the presence of estrogen and progesterone receptors. Prophylactic treatment with cinnamaldehyde increased the tumor latency period and decreased the tumor volume, tumor burden and tumor multiplicity. Compared to DMBA control group, cinnamaldehyde and its nano preparation showed favourable results in terms of tissue antioxidant profiles and plasma biochemical parameters. Mild to moderate regressive changes were observed in various treatment groups. However tamoxifen treated rats showed greater extent of favourable changes in terms of tumor histology. The study revealed that, cinnamaldehyde (CNMA) and nano zinc cinnamaldehyde (CZN) have mild degree of anticancer effects, with CZN being little more effective than CNMA. However CNMA was more effective when used prophylactically than when used as a therapeutic agent. Hence, it is likely that CNMA can reduce the possibility of breast cancer occurrence and severity when used prophylactically.
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    ThesisItemOpen 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, R
    ABSTRACT: 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 predominant