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2010 - 20192
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Subject: Veterinary Pharmacology × End date: 2023 × Type: Thesis × Thesis Type: Ph.D ×
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    ThesisItemOpen Access
    IN VITRO ANTICANCER ACTIVITY OF 6–THIOGUANINE AND 6-THIOGUANINE LOADED CHITOSAN NANOPARTICLES WITH OR WITHOUT CURCUMIN AND PHARMACOKINETIC STUDIES IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA, 2019-08) RASHMI, R; RAVI KUMAR, P(MAJOR); PRAKASH, N; SRINIVASA RAO, G; RAMA DEVI, V; MURALIDHAR, M
    Cancer is the second leading cause of mortality in the world. Cancer nanotherapeutics are rapidly progressing and being implemented to overcome several limitations of conventional drug delivery systems. 6 thioguanine encapsulated chitosan nanoparticles ( 6 – TG – CNPs ) were formulated by ionic - gelation method. Morphologically , the 6 – TG - CNPs were spherical in shape and showed mean size, PDI, z eta potential and e ntrapment eff iciency of 261.63±6.01nm, 0.3 4 ±0.10, + 15.97±0.46mV and 44.27 per cent , respectively. IR spectra confirmed 6 - TG complex with chitosan. In vitro drug release profile of 6 - TG - CNPs revealed slow but increased ( 91.40 ± 1.08 per cent at 48h) release at pH 4.8 compared to less and sustained ( 73.96 ± 1.12 per cent at 48h) release at pH 7.4. MTT assay was conducted on MCF - 7 and PA - 1 cell lines at 48h incubation to determine per cent cell viability . IC 50 values of 6- TG, 6 - TG - CNPs and curcumin for MCF - 7 were 23.09, 17.82 and 15.73μM , respectively. Likewise, IC 50 values of 6 - TG, 6 - TG - CNPs and c urcumin for PA - 1 were 5.81, 3.92 and 12.89μM , respectively. Combination of 6-TG-CNPs (IC25) with curcumin (IC25) on PA-1 and MCF-7 showed percent cell viability of 43.67±0.02 and 49.77±0.05, respectively. The in vitro cytotoxicity potential in terms of per cent cell viability, early apoptosis, G2/M phase arrest and global DNA demethylating activity of 6-TG-CNPs alone and in combination with curcumin proved to be more effective than that of 6-TG on PA-1 cells. The Cmax of 6-TG in 6-TG-CNPs alone and 6-TG-CNPs in curcumin pre-treated groups was found to increased by 1.6-fold and 2-fold, respectively when compared to those observed with 6-TG treated group. The rate and extent of 6-TG absorption was increased by 2.5-fold following 6-TG-CNPs alone and 3.2-fold in curcumin followed by 6-TG-CNPs treated group compared to those observed with 6-TG treated group. The enhanced Cmax and AUC for 6-TG were in the order of curcumin pre-treatment + 6-TG-CNPs>6-TG-CNPs>6-TG groups. The apparent volume of distribution was substantially lower for 6-TG in 6-TG-CNPs alone and 6-TG-CNPs in curcumin pre-treated groups when compared to those observed with 6-TG treated group. Apart from this, volume of distribution at steady-state was also found lower for 6-TG in both the 6-TG-CNPs treated groups. These PK parameters suggests the better tumour targeting efficiency of 6-TG nanoformulations with less toxicity in off-target tissues. Thus, the 6-TG encapsulated chitosan nanoparticles prepared in the present study used either alone or in combination with curcumin present a wide scope for efficient delivery of 6-TG at the target sites.
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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.