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ThesisItem Open Access EVALUATION OF IN-VITRO ANTHELMINTIC ACTIVITY OF CURCUMIN AND PIPERINE NANOPARTICLES(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2022) MADHU R; PAVITHRA. B.H)The present study was carried out with an aim to synthesize and characterize curcumin nanoparticles and piperine nanoparticles and to evaluate the in vitro anthelmintic potential of curcumin- and piperine-nanoparticles against gastrointestinal (GI) nematodes of sheep. Curcumin nanoparticles and piperine nanoparticles were synthesized by using solvent (-) anti-solvent method. Scanning electron microscopy (SEM) analysis showed the average particle size of 32nm and 90nm for curcumin nanoparticles and piperine nanoparticles respectively. Dynamic light scattering (DLS) analysis showed hydrodynamic diameter of 261nm and 228nm for curcumin nanoparticles and piperine nanoparticles respectively. The zeta potential of curcumin nanoparticles and piperine nanoparticles was measured to be -24.9mV and -10.2mV respectively. Polydispersity index of curcumin nanoparticles and piperine nanoparticles was measured to be 25.4 per cent and 24 per cent respectively. Curcumin, piperine, curcumin nanoparticles and piperine nanoparticles were investigated for in vitro anthelmintic potential with albendazole as standard of comparison, against GI nematodes of sheep at various concentrations (0.025, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 μg/mL). The in vitro anthelmintic assays employed in the present study were egg hatch assay (EHA), larval development assay (LDA) and larval motility assay (LMA). The piperine nanoparticles (LC50: 0.035μg/ml) showed the good anthelmintic activity in terms of EHA compared to albendazole (LC50: 0.169μg/ml), showed the good anthelmintic activity in terms of EHA compared to albendazole (LC50: 0.152μg/ml), curcumin (LC50: 0.214μg/ml) and curcumin nanoparticles (LC50: 0.056μg/ml) in the present study. The piperine nanoparticles (LC50: 0.062μg/ml) showed the good anthelmintic activity in terms of LDA compared to albendazole (LC50: 0.142μg/ml), piperine (LC50: 0.169μg/ml), curcumin (LC50: 0.094μg/ml) and curcumin nanoparticles (LC50: 0.071μg/ml) in the present study. The curcumin nanoparticles (LC50: 0.071μg/ml) exhibited good anthelmintic activity in terms of LMA compared to albendazole (LC50: 0.142μg/ml) and curcumin (LC50: 0.094μg/ml), whereas piperine and piperine nanoparticles did not show inhibitory effect on L3 larval motility in the present study. Key words: Curcumin nanoparticles, piperine nanoparticles, in vitro anthelmintic assays.ThesisItem Open Access PHARMACOLOGICAL AND TOXICOLOGICAL STUDIES OF AGERATUM CONYZOIDES IN RATS(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2022) HARISHA, C. B.; SHRIDHAR, N. B.The study was taken up to evaluate the pharmacological and toxicological property of Ageratum conyzoides (A. conyzoides) plant extract in rats. Phytochemical analysis revealed the presence of carbohydrates, proteins, saponins, alkaloids, flavonoids, phenolic compounds, phytosterols and triterpenoids. The in vivo antiinflammatory property of the plant extract was studied using carrageenan induced paw oedema method and the extract at the doses of 1000 and 1500 mg/kg and was having significant anti-inflammatory activity by reducing the paw edema by 33.77 % and 40.26 % respectively compared to standard drug meloxicam which was 46.75 %. In vivo analgesic activity was conducted by using acetic acid induced writhing model and the extract at the doses 1000 and 1500 mg/kg exhibited significant analgesic activity by reducing the writhing response by 35.09 % and 41.22 % respectively compared to standard drug meloxicam which was 48.33%. Acute oral and repeated dose 28-day oral toxicity studies of methanol extract was carried out in Wistar albino rats as per the OECD guidelines 423 and 407 respectively. In sub-acute oral toxicity study, dose levels of 500, 1000 and 1500 mg/kg were administered daily for 28 days and compared with the control rats. In both toxicity studies, no mortality and toxicity signs were observed. The MTD value was found to be more than 5000 mg/kg. The treatment groups did show changes in haematological and biochemical parameters which were evident by histopathological changes in different organs. The plant aerial part extract exhibited substantial anti-inflammatory and analgesic properties, which can be used to investigate the plant's therapeutic efficacy. Key words: Ageratum conyzoides, Phytochemical analysis, Anti-inflammatory activity, Toxicity, Wistar albino rats.ThesisItem Open Access STUDIES ON PHARMACOKINETICS AND SAFETY EVALUATION OF MELOXICAM WITH OR WITHOUT CO-ADMINISTRATION OF ANDROGRAPHOLIDE OR BROMELAIN IN RATS(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2022) ARURU KEERTHANA; SUNIL CHANDRA, U.The present study was designed to evaluate the pharmacokinetic (PK) and safety evaluation of meloxicam (MLX) with or without co-administration of andrographolide (AGL) or bromelain (BRM) in Wistar rats. The pharmacokinetic parameters of MLX in Group I (MLX @ 5 mg.kg-1, p.o.), II (MLX + AGL @ 60 mg.kg-1, p.o) and III (MLX + BRM @ 50 mg.kg-1, p.o) revealed no significant change in observed Tmax of 4 h in all groups (n=8 per group). The PK parameters were analyzed with High Performance Liquid Chromatography (HPLC) and calculated by using PK Solver®, version 2.0. The time vs concentration of MLX data was found best fit in to noncompartmental model. The Cmax of MLX was decreased in Groups II, III compared to Group I. The AUC of MLX was decreased in Groups II and III compared to Group I. The half life of MLX was decreased in Group II, while it had increased in Group III compared with Group I. For the safety evaluation study, the rats were divided into six groups viz: I (control), II (MLX @ 10 mg.kg-1, p.o.), III (AGL @ 60 mg.kg-1, p.o.), IV (BRM @ 50 mg.kg-1, p.o.), V(MLX+AGL) and VI (MLX+BRM). The haematological parameters viz: In Group II, haemoglobin, total erythrocyte count and packed cell volume values were significantly decreased (p<0.05). Liver and kidney function enzymes were increased significantly (p<0.05) in Groups II and VI which was correlated by the histopathology. The study concluded that AGL coadministration had no influence on pharmacokinetics of MLX, while BRM enhanced the half-life of MLX, and there by enhanced the hepatic and renal damage potential of MLX on co-administration indicating the herb drug interactions. Key words: Meloxicam, Andrographolide, Bromelain, Pharmacokinetics, Safety, InteractionsThesisItem Open Access STUDIES ON PHARMACOLOGICAL AND TOXICOLOGICAL ASPECTS OF TRIANTHEMA PORTULACASTRUM IN RATS(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2022) BASAVARAJA, G.D.; SHRIDHAR, N.B.The study was taken up to evaluate the pharmacological and toxicological property of methanolic extract of aerial parts of the plant T. portulacastrum (METP). Phytochemical analysis revealed the presence of carbohydrates, proteins, alkaloids, saponins, flavonoids, phenolic compounds, tannins, phytosterols and triterpenoids. The study was conducted to evaluate the in vivo anti-inflammatory property of methanolic extract of aerial parts of plant T. portulacastrum using carrageenan induced paw oedema model and the extract at the doses of 400 and 600 mg/kg shown to have significant anti-inflammatory activity. In vivo analgesic activity was conducted by using acetic acid induced writhing as peripheral pain model and the extract at the doses 400 and 600 mg/kg showed significant analgesic activity. Acute oral and repeated dose 28-day oral toxicity studies of METP was carried out in Wistar albino rats as per the OECD guidelines 423 and 407 respectively. In sub-acute oral toxicity dose levels of 500, 1000 and 1500 mg/kg were administered daily for 28 days and compared with the control rats. In both toxicity studies, no mortality and toxicity signs were observed. The MTD value was found to be more than 5000 mg/kg. Haematological and biochemical parameters showed no significant changes and these findings correlate with the observed histopathological features in extract treatment groups. The methanolic extract of aerial parts of the plant showed significant antiinflammatory and analgesic property that can be utilized to explore the therapeutic efficacy. Key words: T. portulacastrum, Phytochemical analysis, Anti-inflammatory activity, Analgesic activity, Toxicity study, Wistar albino rats.ThesisItem Open Access TOXICITY STUDY OF FUNGAL CONTAMINATED BREWER’S SPENT GRAIN IN RATS(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2023) JAGADEESH, S.C.; SHRIDHAR, N.B.The present study was undertaken to evaluate the toxicity of fungal contaminated brewer’s spent grain in rats. Repeated dose 28-day oral toxicity study of mycotoxins present in mixed fungal culture filtrates of Rhizopus oryzae 25%, Aspergillus flavus 50% and Aspergillus nomius 25%, was conducted by gavaging it to rats. 40 Wister albino rats were divided in to four groups, 10 rats in each group of either sex. Keeping one group as control, other three groups received the mixed fungal culture filtrates at low dose (0.5 ml/100 g), medium dose (1 ml/100 g) and high dose (2 ml/100 g) rates depending on their body weights respectively. Body weight parameter and blood samples were taken on day 0, 14 and 28 days of the study. Biochemical parameters like ALT, AST, BUN, creatinine and haematological parameters like TLC, TEC, Hb, PCV and Blood clotting time were analysed. Significant (P<0.05) decrease in body weight, significant (P<0.05) increase in ALT, AST, BUN and Creatinine serum concentration, a significant (P<0.05) fall in TLC, TEC, Hb and PCV with significant (P<0.05) increase in blood clotting time in treatment groups compared to control group rats were observed. The gross and histopathological changes revealed, hepatotoxicity, nephrotoxicity, immunotoxicity, and cardiotoxicity in all the treatment groups. Thus, it was concluded from the observations in the present study that, the fungal culture filtrate had shown toxicity in rats, attributed to the presence of toxic principle in mixed fungal culture filtrates. Key words: Brewer’s spent grain, Toxicity, Rat, Rhizopus oryzae, Aspergillus flavus, Aspergillus nomiusThesisItem Open Access TOXICITY STUDY OF FUNGAL INFESTED RAGI STRAW IN RATS(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2022) NIRANJANA, S.; SHRIDHAR, N. B.The present study was designed to assess the toxicity of fungal-contaminated ragi straw in rats. Aspergillus flavus and Rhizopus oryzae were the isolated fungi in the fungal-contaminated ragi straw samples. Potato dextrose (PD) broth myceliumfree culture filtrate obtained by these fungi, analyzed for mycotoxins by HPLC-FLD (High Performance Liquid Chromatography-with Fluorescence Detector) method, detected aflatoxin B1 at concentration 279.0 μg/kg. The ragi straw feed sample revealed aflatoxin B1, B2, G1 and G2 at trace concentrations. Repeated dose 28-day oral toxicity study (as per OECD 407 guidelines) was conducted in three groups (n= 10 per group) Wister rats of both sexes. Mixed fungal culture filtrates (1:1 ratio) were gavaged in doses of 0.5 (Low dose), 1(Medium dose) and 2 ml (High dose)/100g of body weight in Group I, II and III respectively and were monitored for signs of toxicity. Body weights were recorded and blood samples were taken on day 0, 14th and 28th for haematological and biochemical parameters analysis. There was significantly (p<0.05) decrease in Hb, PCV and TEC. Blood clotting time , AST, ALT, BUN, creatinine were significantly (p<0.05) increased in Group II, III. Gross and histopathological abnormalities correlated with the fungal culture filtrate's hepatotoxicity, cardiotoxicity and nephrotoxicity. It was concluded that the fungal culture filtrate was toxic to rats, which was linked to the existence of a toxic component, feeding of such fungal contaminated ragi straw might adversely affect the cattle health in terms of reduced production and performance. Key words: Ragi straw, Toxicity, Aspergillus flavus, Rhizopus oryzae, Rat.ThesisItem Open Access PHARMACOLOGICAL AND TOXICOLOGICAL STUDIES OF AESCHYNOMENE AMERICANA IN RATS(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2021) MANIKANTH C.L; N. B. SHRIDHARThe study was designed to evaluate the pharmacological and toxicological properties of Aeschynomene americana plant. Phytochemical analysis revealed the presence of carbohydrates, starch, flavonoids, phenols, tannins, phytosterols, triterpenoids, chalcones and coumarin. Evaluation of the in vivo anti-inflammatory property of the plant extract at doses 250, 500 and 1000 mg/kg using carrageenan induced paw oedema model revealed significant anti-inflammatory activity. In vivo analgesic activity was assessed by inhibition of writhing induced by acetic acid as peripheral pain model and the extract at the doses 500 and 1000 mg/kg showed significant analgesic activity. Acute oral and repeated dose 28-day oral toxicity studies of methanolic extract was carried out in Wistar albino rats as per the OECD guidelines 423 and 407 respectively. In acute toxicity a dose level of 2000 mg/kg was studied. In repeated dose 28-day oral toxicity study dose levels of 300, 600 and 1200 mg/kg were administered daily and compared with the control rats. In toxicity studies, no mortality and toxicity signs were observed grossly but cellular changes observed in histopathology. Except for decrease in platelet and increase in AST in 28-day oral toxicity study, haematological and biochemical parameters were within the reference range in both the studies. Histopathology revealed dose dependent prominent congestive and haemorrhagic changes in repeated dose study. The plant showed significant anti-inflammatory and analgesic property that can be utilized to explore the therapeutic efficacy but with caution as it revealed toxicity as well. Key words: Aeschynomene americana, Phytochemical analysis, Anti-inflammatory activity, Toxicity study, Wistar albino rats.ThesisItem Open Access Punith(KVAFSU, Bidar, 2019) punithThe study was taken up to evaluate the pharmacological and toxicological property of Phaseolus lunatus (P. lunatus) plant. Phytochemical analysis revealed the presence of carbohydrates, proteins, saponins, alkaloids, flavonoids and phenolic compounds. The study was conducted to evaluate the in vivo anti-inflammatory property of the plant extract using carrageenan induced paw oedema and the extract at the doses of 400 and 600 mg/kg is having significant anti-inflammatory activity. In vivo analgesic activity was conducted by using acetic acid induced writhings as peripheral pain model and the extract at the doses 400 and 600 mg/kg showed significant analgesic activity. Acute oral and repeated dose 28 day oral toxicity studies of methanol extract was carried out in Wistar albino rats as per the OECD guidelines 423 and 407 respectively. In sub-acute oral toxicity dose levels of 200, 400 and 600 mg/kg were administered daily for 28 days and compared with the control rats. In both toxicity studies, no toxicity signs and mortality were observed. The MTD value was found to be more than 5000 mg/kg. No significant (p<0.05) changes in haematological parameters and biochemical parameters showed significant (p<0.05) changes. Evident histopathological changes observed in extract treated groups. The plant leaves showed significant anti-inflammatory and analgesic property that can be utilized to explore the therapeutic efficacy. Keywords: Phaseoluslunatus, phytochemical analysis, Anti-inflammatory activity, Analgesic activity, Toxicity study, Wistaralbino rats.ThesisItem Open Access STUDIES ON NEUROBIOCHEMICAL AND NEUROPHARMACOLOGICAL ACTIVITIES IN WISTAR RATS EXPOSED TO ARSENIC WITH OR WITHOUT EXOGENOUS MELATONIN ADMINISTRATION(KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR, 2017-08) PRASADA NINGAPPA DURAPPANAVAR; PRAKASH NADOOR)(‘As’) induced alterations in neurobiochemestry in brain and its impact on neuropharmacological activities with or without the melatonin (MLT) as an antioxidant given exogenously. Male Wistar rats were randomly divided in to four groups of six each. Group-I served as untreated control, while group-II received ‘As’ [sodium (meta) arsenite; NaAsO2] @ 10 mg.kg-1 b.wt. (p.o) for a period of 56 days. Experimental rats in group-III received treatment similar to group-II but in addition received MLT @ 10 mg.kg-1 b.wt. (p.o) from day 32 onwards. Rats in group-IV received MLT alone from day 32 onwards similar to group-III. Sub-chronic exposure to ‘As’ (group-II) significantly (p0.05) reduction in pain latency. Sub-chronic administration of ‘As’ induced (group-II) significant (p<0.05) increase in the levels of thiobarbituric acid reactive substance (TBARS) called malondialdehyde (MDA) in the brain tissue (5.55±0.57 nmol.g-1), and their levels were significantly (p<0.05) reduced by MLT supplementation (group-III: 3.96±0.15 nmol.g-1). The increase in 3-nitrotyrosine (3-NT) levels in ‘As’ exposed rats indicated nitrosative stress due to the formation of peroxynitrite (ONOO-). However, exogenously given MLT significantly (p<0.05) reduced the 3-NT formation as well as prostaglandin (PGE2) levels in the brain. Similarly MLT administration have suppressed the release of pro-inflammatory cytokines (viz., IL-1β, IL-6 & TNF-α) and amyloid-β1-40 (Aβ) deposition in the brain tissues of experimental rats. To conclude, exogenous administration of melatonin can overcome the sub-chronic arsenic induced oxidative and nitrosative stress in the CNS, suppressed pro-inflammatory cytokines and restored certain disturbed neuropharmacological activities in Wistar rats. Key words: Arsenic (As), Neuropharmacology, Melatonin, Oxidative stress, Wistar rats
