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  • ThesisItemOpen Access
    COGNITIVE AND NEURO-ENDOCRINE DISRUPTION OF LEAD AND MONOCROTOPHOS AND THEIR RELATION TO THYROTOXICITY IN PERINATALLY EXPOSED RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY , TIRUPATI – 517502. (A.P.) INDIA, 2010-06) KALA KUMAR, B. D. P; GOPALA REDDY, A (Major); RAVI KUMAR, P; KONDAL REDDY, K; ANAND KUMAR, A
    ABSTRACT : Thyroid hormone is essential for neuronal and glial genesis and also the time specific migration of neurons. Any change in the sequential neurodevelopment of foetus or the neonate would be manifested as behavioural abnormality in the adult life. In utero exposure to xenobiotics would interfere with the availability of maternal thyroid hormone to the foetus. Pesticides and heavy metals form a major chunk of the environmental pollutants that affect the behaviour of animals and human beings. Monocrotophos a widely used pesticide and lead a ubiquitous heavy metal are known neurotoxicants. The role of these two substances in thyroid disruption and subsequent developmental neurotoxicity was studied. Thirty pregnant female rats were divided into five groups. Group I was Sham. Methimazole (II), monocrotophos (III), lead acetate (IV) were administered singly and in combination (V) to assess the interaction. AChE, thyroid profile (TSH, T3 and T4), maternal behaviour, litter size, neonatal mortality, neurodevelopmental (brain wet weights, DNA, RNA and protein), neurobehavioural (auditory startle response, rope descent, mid air righting reflex, elevated plus maze, photoactometry and morris water maze) and neurochemical (acetyl choline and glutamate content of the brain) parameters were studied. Histopathology of thyroid and brain were conducted. Inhibition of AChE was < 20% in III and V. Thyroid profile decreased in II and T4 increased in IV. Maternal behaviour was significantly (p<0.01) interfered in III and V. Neurodevelopmental and neurobehavioural parameters did not reveal significant changes. Glutamate content was highest in group V indicating excitotoxicity. Thyroid was affected significantly in II, III and IV but not in V. Cerebral cortical layers were affected in groups II through V. The three layers of cerebellum either had abnormal arrangement or decreased cellularity in all treated groups. Thus, it is concluded that monocrotophos and lead acetate could act as thyroid disruptors and might have interfered with neurodevelopment during the perinatal exposure. Group V also affected neurodevelopment but did not affect thyroid histology suggesting other mechanisms could have contributed to the neurotoxicity.
  • ThesisItemOpen 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, P
    ABSTRACT : 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.
  • ThesisItemOpen Access
    STUDIES ON THE PROTECTIVE AND ANTIOXIDANT EFFECTS OF AN APHRODISIAC HERB “TRIBULUS TERRESTRIS” ON CADMIUM INDUCED TESTICULAR DAMAGE.
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2010-06) RAJENDAR, B; BHARAVI, K (Major); SRINIVASA RAO, G; KISHORE, P. V. S.
    ABSTRACT : The present study was aimed to evaluate the protective effect of Tribulus terrestris (TT) on Cadmium (Cd) induced toxicity in rats. Forty adult male rats were divided into 4 groups with ten in each group and treatment given as follows: group I (Control) received double distilled water; group II (Cd toxic) received CdCl2 @ 3 mg/kg b.wt s/c at weekly interval for 6 weeks, group III (TT treatment) received CdCl2 @ 3 mg/kg b.wt s/c at weekly interval for 6 weeks and a daily oral dose of ethanolic extract of TT @ 5 mg/kg b. wt and group IV (Vit-E treatment) received CdCl2 @ 3 mg/kg b.wt s/c at weekly interval and daily oral dose of Vit-E @ 75 mg/kg b. wt. At the end of 6th week rats were sacrificed and testes were collected and estimated the organ weight, testicular tissue peroxidation markers, antioxidant markers, and functional markers, concentration of Cd, histomorphometry and histopathology. Phytochemical screening of ethanolic extract of TT revealed the presence of flavonoids, tannins, saponins, polyphenols and steroids. In Cd toxic group rats weekly average body weight gain and testicular weights were significantly reduced. The testicular tissue antioxidants such as SOD, CAT and GSH were significantly reduced; the peroxidation markers such as TBARS and protein carbonyls were significantly increased and the functional markers such as ALP and LDH were also significantly reduced in Cd administered group. Cd significantly altered the histological structures; histomorphometry revealed significant reduction in number of spermatogonia, resting spermatocytes, pachytene spermatocytes, spermatids, and leydig cells in seminiferous tubules. Seminiferous tubular diameter was also reduced along with pathological changes of disruption of basement membrane and tubular epithelium, formation of gaint cells, vacuolation in Sertoli cells. Treatment of Cd toxic rats with ethanolic extract of TT significantly reversed the weekly body weight gain, testicular weights, testicular tissue peroxidation markers, antioxidant markers and functional markers and also significantly reversed the histopathological and histomorphometric observations. Vitamin-E treatment to Cd intoxicated rats all the antioxidant, peroxidation and functional markers reversed significantly compared to the Cd toxic group and also to the TT treated group. Histoarchitecture was near normal. With this study, it is concluded that Cd accumulates in testicular tissues and induced toxicity through induction of oxidative stress. Supplementation of TT was offered moderate protection compared to Vitamin E.
  • ThesisItemOpen Access
    Pharmacokinetic interaction studies between breast cancer resistance protein (BCRP) inhibiting flavonoids and ciprofloxacin in rats
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA, 2010-07) KASTURI DEVI, K; SRINIVASA RAO, G (Major); RAVI KUMAR, P; ANANDA KUMAR, P
    ABSTRACT : Pharmacokinetic interaction between ciprofloxacin, an antibacterial fluoroquinolone that was described as a substrate for breast cancer resistance protein (BCRP) and BCRP inhibiting flavonoids curcumin and quercetin in rats was investigated in the present study. Male Wistar albino rats, weighing about 200-250g were randomly divided into three groups consisting six rats in each group. Rats in group I (control) received ciprofloxacin alone (10 mg.kg-1 PO). Group II received curcumin (400 mg.kg-1, PO) 30 min prior to administration of ciprofloxacin. Similarly Group III received ciprofloxacin 30 min after pretreatment with quercetin (20 mg.kg-1, PO). Rats were anaesthetized after ciprofloxacin administration for blood collection with a Xylazine-Ketamine combination. Blood samples were collected from jugular vein and tail clipping at predetermined time intervals prior to and at 0.33, 0.67, 1, 1.5, 2, 4, 6, 8 and 12 h time intervals after administration of ciprofloxacin. Plasma was separated by centrifuging at 3000 RPM for 10 min and stored at -200c until analyzed for ciprofloxacin by microbiological assay using Escherichia coli (ATCC 25922). Based on plasma concentrations the pharmacokinetic parameters were determined by non compartmental methods. Detectable plasma concentrations of ciprofloxacin in rats persisted upto 6 h when ciprofloxacin was given alone where as ciprofloxacin was detectable upto 8 h in both curcumin and quercetin pretreated rats. Cmax of ciprofloxacin in group I was 1.12±0.18 μg.mL-1. There was significant increase in Cmax of ciprofloxacin in both curcumin (Group II: 1.74±0.052 μg.mL-1) and quercetin (Group III: 1.99±0.1 μg.mL-1) pretreated rats. Important pharmacokinetic parameters obtained for ciprofloxacin after its oral administration in group I (control) by non compartmental analyses were: elimination rate constant (β) 0.40±0.049 h-1; elimination half life (t½β) 1.85±0.22 h; area under plasma concentration time curve (AUC0-∞) 2.38±0.31 μg.h.mL-1 ; area under first moment curve (AUMC0-∞) 6.26±1.24 μg.h 2.mL-1; steady state volume of distribution (Vdss) 10.98±0.78 L.kg-1; total body clearance (ClB) 4.56±0.55 L.kg-1.h -1; and Mean residence time (MRT) 2.52±0.2 h. In group II the pharmacokinetic parameters for ciprofloxacin in curcumin pretreated rats were : β, 0.237±0.037 h-1; t½β, 3.49±0.77 h; AUC0-∞, 6.03±1.01 μg.h.mL-1; AUMC0-∞, 35.37±15.10 μg.h 2.mL-1; Vdss, 8.31±0.82 L.kg-1; ClB, 1.83±0.22 L.kg-1.h -1 ; MRT, 5.03±1.06 h. It was found that there was a significant increase (p<0.01) in Cmax, , longer MRT and t½β indicated the tendency of ciprofloxacin retention in plasma of rats when pretreated with curcumin . In group III pharmacokinetic parameters for ciprofloxacin in quercetin pretreated rats were: β, 0.298±0.029 h-1; t½β, 2.00±0.38 h; AUC0-∞, 4.55±0.27 μg.h.mL-1; AUMC0-∞, 13.19±1.14 μg.h 2.mL-1; Vdss, 6.48±0.51 L.kg-1; ClB, 2.23±0.14 L.kg-1.h -1 ; MRT, 2.88±0.15 h. A significant increase (P<0.01) in Cmax, AUC0-∞ and a significant decrease (p<0.01) in clearance for ciprofloxacin was found in rats when pretreated with quercetin. Thus results of the present study indicated that pretreatment with curcumin and quercetin significantly increased the concentrations of ciprofloxacin in rats. Thus it is evident that BCRP inhibiting flavonoids like curcumin and quercetin enhance the retention time of ciprofloxacin in plasma, which in turn improves the clinical efficacy of ciprofloxacin against susceptible bacterial infections.
  • ThesisItemOpen Access
    EFFECT OF Trigonella foenum graecum (FENUGREEK) AGAINST HYPERLIPIDEMIAS IN OVARIECTOMIZED RATS
    (Sri Venkateswara Veterinary University, TIRUPATI – 517 502,A.P, 2010-07) NAGA SRUJAN V, RAYAPROLU; ADILAXMAMMA, K (Major); GOPALA REDDY, A; ESWARA PRASAD, P
    ABSTRACT : Recognition of hypercholesterolemia as a risk factor for cardiovascular diseases leads to the development of drugs that reduce serum cholesterol levels. Plant kingdom is a rich natural source for many therapeutic molecules of which Trigonella foenum graecum (Fenugreek) seeds are reported to possess hypolipidemic activity in diet induced and diabetic induced models. However, no reports are available on the hypolipidemic potential of fenugreek in an ovariectomized rat model. Experimental studies were conducted to evaluate the ameliorating effects of propanolic extract of Trigonella foenum graecum (Fenugreek) seeds in ovarian hormone deficiency induced hyperlipidemia in comparision with atorvastatin. Thirty female wistar rats were divided into five groups i.e., group I – normal control (sham operated), group II – ovariectomized rats (OVX), group III – OVX+Fenugreek extract (1 g/kg b.wt), group IV – OVX+Fenugreek (4 g/kg b.wt) and OVX+Atorvastatin (1.2 mg/kg b.wt p.o.). Body weights were taken at weekly interval. Blood was collected from 8 h fasted animals on days 14, 28, 42 and 56 for the estimation of serum biochemical profile (Lipid profile and glucose). At the end of the experimental period, the rats were sacrificed
  • ThesisItemOpen Access
    Studies on the Pharmacokinetic Interaction between Meloxicam and Quercetin, a CYP2C9 and CYP3A4 Inhibiting Flavonoid, in Rabbits
    (Sri Venkateswara Veterinary University, TIRUPATI – 517 502,A.P, 2010-07) JAYAKANTH, K; ADILAXMAMMA, K (Major); RAVI KUMAR, P; SURESH KUMAR, R.V
    ABSTRACT : The present study was aimed to investigate the pharmacokinetic interaction between meloxicam and quercetin, a CYP2C9 and CYP 3A4 inhibiting flavonoid, in rabbits. Fifteen male rabbits were divided into three groups with five animals in each group and the treatment was given as follows: group I (Control) received meloxicam alone @ 1.5 mg/kg b.wt orally; Group II received meloxicam @ 1.5 mg/kg b.wt orally 30 minutes after the pretreatment with quercetin orally @ 10mg/kg b.wt; group III received meloxicam @ 1.5 mg/kg b.wt orally 30 minutes after the pretreatment with quercetin orally @ 20mg/kg b.wt. Blood was collected by veinipuncture at 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 h. Plasma was separated by centrifuging the blood and was subjected to HPLC assay for estimation of meloxicam. Important pharmacokinetic parameters after non compartmental analysis were t1/2B, 14.52 ± 4.4 h; ClB, 0.1 ± 0.01 L.kg-1.h-1; AUC0-∞,16.02 ± 1.95 μg.h.mL-1; Vdss,1.97 ± 0.24 L.kg-1: and MRT, 21.89±5.32 h in group I, t1/2B, 11.46 ± 1.62 h; ClB, 0.1± 0.01 L.kg-1.h-1; AUC0-∞,15.40 ± 1.18 μg.h.mL-1; Vdss,1.83 ± 0.24 L.kg-1: and MRT, 18.1 ± 1.8 h in group II and t1/2B, 9.93 ± 0.59 h; ClB, 0.07 ± 0.01 L.kg-1.h-1; AUC0-∞,21.08 ± 1.36 μg.h.mL-1; Vdss,1.14 ± 0.11 L.kg-1: and MRT, 15.58 ± 0.64 h in group III. The results in present study indicate that the quercetin pretreatment at 10 mg.kg-1 has no significant effect on the pharmacokinetic profile of meloxicam in rabbits where as the quercetin pretreatment at 20 mg.kg-1 has affected the pharmacokinetic parameters.
  • ThesisItemOpen Access
    EFFECT OF Cicer arientinum L. (BENGALGRAM) AGAINST HYPERLIPIDEMIAS IN OVARIECTOMIZED RATS
    (Sri Venkateswara Veterinary University, TIRUPATI – 517 502,A.P, 2010-07) HARINI, S; ADILAXMAMMA, K (Major); MADAN MOHAN, E; SRILATHA, Ch
    ABSTRACT : Experimental studies were conducted to evaluate the ameliorating effects of germinated Cicer arientinum (Bengalgram seeds) in ovarian hormone deficiency induced hyperlipidemia and its effect was compared with atorvastatin. Twenty four female wistar rats were divided into four groups i.e., group I – normal control (sham operated), group II – ovariectomized rats (OVX), group III – OVX+Bengalgram (20% germinated seeds in diet-II) and group IV – OVX+Atorvastatin (1.2 mg/kg b.wt p.o.). Body weights were taken at weekly interval. Blood was collected on day 14, 28, 42, and 56 for the estimation of serum Lipid profile and glucose. At the end of the experimental period, the rats were sacrificed and organs were collected and weighed. Liver lipid profile was studied and liver, aorta and uterine samples were collected for histopathological examination. There was a significant (p<0.05) increase in the serum total cholesterol and non-HDL cholesterol in group II than other groups and serum HDL concentrations significantly (p<0.05) increased in groups III and IV w.r.t group II. The triglyceride levels were low in group III but significantly high in group IV and not much significant differences were noticed in glucose concentrations among the groups. There was a significant (p<0.05) decrease in the uterine weights in group II. The liver lipid profile revealed significant (p<0.05) increase in total lipids, total cholesterol and phospholipids in group II compared to group I, where as they significantly (p<0.05) decreased in group III when compare to group II. The liver lipid profile of group III was almost similar to group IV. Triglyceride levels in the liver significantly (p<0.05) increased in group I than group II and III. Histopathological studies revealed fatty degeneration of liver, atrophy of uterus and mild sub-intimal fat accumulation in aorta of group II, where as these changes were ameliorated in group III. In conclusion, the present study revealed that the germinated bengalgram seeds have significant hypolipidemic action and a significant (p<0.05) increase in the uterine weights in ovariectomized rats without any histopathological changes. This may be attributed to the presence of phytoestrogens in the germinated bengalgram seeds.