Thumbnail Image

Anand Agricultural University, Anand

Anand Agricultural University (AAU) was established in 2004 at Anand with the support of the Government of Gujarat, Act No.(Guj 5 of 2004) dated April 29, 2004. Caved out of the erstwhile Gujarat Agricultural University (GAU), the dream institution of Sardar Vallabhbhai Patel and Dr. K. M. Munshi, the AAU was set up to provide support to the farming community in three facets namely education, research and extension activities in Agriculture, Horticulture Engineering, product Processing and Home Science. At present there seven Colleges, seventeen Research Centers and six Extension Education Institute working in nine districts of Gujarat namely Ahmedabad, Anand, Dahod, Kheda, Panchmahal, Vadodara, Mahisagar, Botad and Chhotaudepur AAU's activities have expanded to span newer commodity sectors such as soil health card, bio-diesel, medicinal plants apart from the mandatory ones like rice, maize, tobacco, vegetable crops, fruit crops, forage crops, animal breeding, nutrition and dairy products etc. the core of AAU's operating philosophy however, continues to create the partnership between the rural people and committed academic as the basic for sustainable rural development. In pursuing its various programmes AAU's overall mission is to promote sustainable growth and economic independence in rural society. AAU aims to do this through education, research and extension education. Thus, AAU works towards the empowerment of the farmers.

Browse

2004 - 200926
Reset filters
Subject: Veterinary Pharmacology and Toxicology × End date: 2009 × Start date: 2004 ×
Reset filters

Search Results

Now showing 1 - 9 of 26
  • Thumbnail Image
    ThesisItemOpen Access
    STUDIES ON EFFECT OF KETOPROFEN AND FEBRILE CONDITION ON PHARMACOKINETICS OF LEVOFLOXACIN AND SAFETY OF LEVOFLOXACIN ALONE AND IN COMBINATION WITH KETOPROFEN IN SHEEP
    (AAU, Anand, 2009) PATEL, URVESHKUMAR DAHYABHAI; Thaker, A. M.
    Levofloxacin is a novel third generation fluoroquinolone with broad spectrum antibacterial activity. Use of non-steroidal anti-inflammatory drugs (NSAIDs) are frequently recommended with antibacterials for the treatment of various bacterial infections accompanied by fever and other inflammatory conditions in animals. Ketoprofen (KTP) is an aryl propionic acid derivative, non-selective COX inhibitor NSAID having anti-inflammatory, analgesic and antipyretic properties. In veterinary practice, ketoprofen is used to lower body temperature in animals having fever, to relieve bacteremia and pain in all animals. Pharmacokinetics of an antibacterial drug may change when administered with anti-inflammatory drug or in febrile animals. Despite the great potential for clinical use of levofloxacin, the data on its pharmacokinetics and safety profile in sheep are scarce. The present study was planned to determine the effect of intramuscularly administered ketoprofen (3 mg/kg) and febrile condition (lipopolysaccharide (LPS) induced) on pharmacokinetics of levofloxacin following intravenous, subcutaneous and oral administration (3 mg/kg) in sheep and safety of daily intravenous administration of levofloxacin alone (3 mg/kg) and in combination with intramuscular administration of ketoprofen (3 mg/kg) for five days in sheep by monitoring haematological and blood biochemical profiles.
  • Thumbnail Image
    ThesisItemOpen Access
    IMMUNOTOXICOLOGICAL STUDIES OF SUBACUTE ACEPHATE EXPOSURE IN WHITE LEGHORN COCKEREL BIRDS
    (AAU, Anand, 2006) TRIPATHI, SYAMANTAK MANI; THAKER, A. M.
    Acephate (Ace), a water-soluble insecticide, belongs to the phosphoramidothioate group of organophosphate (OP) insecticides. Acephate is an organophosphate foliar spray insecticide of moderate persistence with residual systemic activity of about 10-15 days. It is being widely used for the protection of vegetables and fruits due to its activity against lepidopterans and aphids. As this insecticide is in use as crop protectant, it is likely to cause indirect exposure in poultry through contamination of feed, soil and ground water (in very low amount) and hence, the present study was conducted in Day old White Leghorn Cockerels birds; approximate medium lethal dose (ALD50) of Acephate taken into consideration for the study was 852mg/kg. One hundred twenty five birds were divided into five different groups each comprising 25 birds. The birds of group Ci were given no treatment and served as control. Group C2 were administered groundnut oil (Iml/kg) and served as control (vehicle). Group T1 was put onl/40th of ALD50 (21.3 mg/kg), while group T2 received 1/30th of ALD50 (28.4 mg/kg) and group T3 was administered withl/20th of ALD50 (42.6 mg/kg) of Acephate suspended in 1 ml of groundnut oil. Once daily oral dosing was carried out for 28 days. All the birds were monitored for any observable toxic symptoms throughout the experimental period and they were also weighed weekly to monitor body weight gain. The blood samples were collected before sacrificing the birds on day 15 (after 14 days oral dosing) and day 29 (after 28 days oral dosing) of the study and were analyzed for hematological, biochemical and immunological parameters. Organ (liver, spleen, bursa and thymus) weights were recorded and organs (liver, spleen, bursa thymus, lung, and kidney) were collected for histopathological examinations. Severity and extent of the clinical signs varied according to dosage administered to the birds. The clinical symptoms observed were sudden onset of depression, reduced feed intake, dullness, ruffled feathers, cyanosis of comb, green diarrhea and severe limb weakness and some time paralysis. During the study period 6-8 birds died. Nervine symptoms like tremor, head down condition and torticolis were noticed only for few minutes before death. There was a reduction in the body weight of the Acephate treated birds. No alteration had been recorded in haematological parameters (hemoglobin, packed cell volume, total erythrocyte count and total leukocyte count) due to Acephate exposure. Dose dependent significant increase in blood glucose due to administration of Acephate was observed. A significant dose dependent increase in Serum Glutamic Oxaloacetate Transaminase and Serum Glutamic Pyruvate Transaminase and non significant increase in Lactate Dehydrogenase level of the birds treated with the Acephate indicates its systemic effect. A significant decrease in serum proteins during study was observed. A significant decrease in serum albumin and globulin were observed on 28th day of study. During the experimentation, Acephate had dose dependent immunosuppressive effect on Humoral immune response of birds from 28th day of experimentation. These findings indicate significant effect on protein metabolism and humoral immune response at the administered doses of Acephate. Cellular immunity was not affected as tested by DNCB dye test. Present study revealed that Acephate at administered doses seems to be toxic for multiple systems in growing WLH birds. Gross postmortem and histopathological changes in various organs of birds treated with Acephate were observed with typical organophosphate dose dependent toxicity signs. Microscopic changes observed in different organs viz. liver, lung, kidney spleen, thymus and bursa were of typical to organophosphate insecticide poisoning. Though, Acephate has been reported mild to moderately toxic to the birds; it seems that doses of Acephate given in the present study produce mild toxicity to multiple body systems of growing birds including immune system.
  • Thumbnail Image
    ThesisItemOpen Access
    TOXICOLOGICAL STUDIES OF SHROT TERM EXPOSURE OF BANTAMIZED WHITE LEGHORN BIRDS TO ACEPHATE
    (AAU, Anand, 2005) PATEL, NILENKUMAR P.; Thaker, A. M.
    The present study was conducted in 8 to 10 week old Bantamized White Leghorn birds; approximate medium lethal dose (ALD50) of Acephate use for the study was 852mg/kg. Ninety birds were divided into six different groups. The birds of group Ci was given no treatment and served as control. Group C2 was administered groundnut oil (1 ml/kg) and served as control (vehicle). Group T1 was given l/10th of ALD50 (85.2 mg/kg). Group T2 was put on 1/20th of ALD50 (42.6 mg/kg), while group T3 received 1/30th of ALD50 (28.4 mg/kg) and group T4 was administered with 1/40th of ALD50 (21.3 mg/kg) of Acephate suspended in 1 ml of groundnut oil. Once daily oral dosing was carried out for 28 days. All the birds were monitored for any observable toxic symptoms throughout the experimental period and they were also weighed weekly to monitor body weight gain. The blood samples were collected from wing vein at weekly interval and were analyzed for haematological and biochemical parameters. After 28 days of administration of Acephate birds were sacrificed and organs (lung, liver, spleen, heart, kidney, brain and testes) were collected for histopathological examinations. Severity and extent of the clinical signs varied according to dosage administered to the birds. The clinical symptoms observed were sudden onset of depression, reduced feed intake, dullness, ruffled feathers, cyanosis of comb, green diarrhea and severe limb weakness and some time paralysis. Mortality was observed from third week which was in dose dependent manner. Nervine symptoms like tremor, head down condition and torticolis were noticed only for few minutes before death. There was a reduction in the body weight of the insecticide treated birds. No alteration had been recorded in haematological parameters (hemoglobin, packed cell volume, total erythrocyte count and total leukocyte count) due to Acephate exposure. Dose dependent significant increase in blood glucose due to administration of Acephate was observed. A significant dose dependent increase in Serum Glutamic Oxaloacetic Transaminase and Serum Glutamic Pyruvate Transaminase level of the birds treated with the insecticide after 7 days of treatment indicates their systemic effect. Increase in the triglyceride was observed in treated birds. A significant decrease in serum proteins during study was recorded. Dose dependent increase in the alkaline phosphatase was observed. During the experimentation, Acephate at all the doses inhibited acetylcholinesterase indicating neurotoxicity due to administration of Acephate. Present study revealed that though Acephate is moderately toxic to the birds; it seems to be toxic for multiple systems in growing birds at given dosage. Gross postmortem and histopathological changes in various organs of birds treated with Acephate were observed with typical organophosphate dose dependent toxicity signs. Microscopic changes observed in different organs viz. lung, liver, spleen, heart, kidney, testis and brain which were typical to insecticide poisoning. Though Acephate has been reported moderately toxic to the birds at the doses administered in this study produce toxicity to multiple systems of growing birds used in the study
  • Thumbnail Image
    ThesisItemOpen Access
    Comparative Evaluation of Dexamethasone Induced CYP3A and CYP2H1 Gene Expression by Quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Leghorn Chicks
    (AAU, Anand, 2004) KALIA, ANIL KUMAR; Sarvaiya, J. G.
    The present work was planned to study induction of CYP3A and CYP2HI genes by Reverse Transcriptase polymerase chain reaction (RT-PCR) and Quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Legiiorn chicles. Total RNA was extracted from the liver tissue samples using Tri Reagent based method. The quantity of extracted RNA was assessed spectrophotometrically at 260/280nm, and it ranged from 1.7 to 2.0 OD suggesting good quantity of RNA extraction. The quality of extracted RNA was checked by 1% formaldehyde agarose gel electrophoresis and it showed bands at 28s, 18s and 5s rRNA subunits suggesting good integrity of RNA. First strand cDNA was synthesized using one step RT-PCR Kit. The PCR was performed and the product was subjected to agarose gel electrophoresis which yielded targeted amplification of 1107 bp, 1567 bp and 486 bp amplicon for CYP3A, CYP2HI and p-actin genes, respectively. β-actin (house keeping gene) was used as an internal control for normalization of CYP3A and CYP2H1 gene transcripts. Quantitative RT-PCR was done to quantify gene expression level of CYP3A and CYP2H1 genes. Four end points were selected for sample dropping at 26th, 31st 36rd and 41st cycles to perform Quantitative RT-PCR. The quantity of expressed genes was detected by Gene tool software using 1 kb DNA ladder having concentration of 7.1 ng/0.5 μl at 500 bp as reference. Relative expression ratio of CYP3A and CYP2H1 genes was calculated by Relative Expression Software Tool (REST), It was found that CYP3A is up regulated by a factor of 1.271 and 1.2 in Bantam and White Leghorn chicks, respectively and down regulated by a factor of 11.385 in Bantamized White Leghorn chicks. In Bantamized White Leghorn and White Leghorn chicks CYP2H1 gene was down regulated by factor 1.68 and 1.3 respectively, but up regulated by a factor of 1.126 in case of Bantam chicks. The PCR efficiency ranged from 1.4 to 1.9, 1.36 to 1.8 and 1.36 to 4.4 for CYP3A, CYP2H1 and P-actin genes, respectively in Bantam, Bantamized White leghorn and White Leghorn chicks.
  • Thumbnail Image
    ThesisItemOpen Access
    PHARMACOKINETIC INTERACTIONS OF TOLFENAMIC ACID AND MOXIFLOXACIN AND SAFETY OF TOLFENAMIC ACID IN WISTAR RATS
    (AAU, Anand, 2009) PATEL, SATISHKUMAR DAHYALAL; Thaker, A. M.
    Drug interactions may occur when two drugs are concurrently administered and one drug (or both) may influence the time course of the other in the body. Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibacterial agents are prominent among the groups of drugs commonly prescribed together in veterinary medicine and they have enormous potential for drug interactions. Tolfenamic acid is a non-steroidal anti-inflammatory drug (NSAID) of the fenamate sub-group. Moxifloxacin is a novel fourth generation fluoroquinolone with broad spectrum antibacterial activity. The pharmacokinetic of tolfenamic acid (4.0 mg/kg) and moxifloxacin (5 mg/kg) as single drug and in combination after its intramuscular administration was investigated in male and female wistar rats. Tolfenamic acid and moxifloxacin were assayed in plasma by LC-MS/MS. Pharmacokinetic parameters were calculated by noncompartmental technique using computer software (WinNonlin, version 5.0.1). The present study also evaluated safety of tolfenamic acid (4 mg/kg) alone and in combination with moxifloxacin (5.0 mg/kg) after repeated administration at 24 h interval for 14 days in male and female wistar rats. The mean observed peak plasma concentration of tolfenamic acid following its administration as single drug and in combination with moxifloxacin in male rats were 4111.44 ± 493.15 and 3837.69 ± 351.83 ng/ml, where as in female rats mean values were 7114.74± 1409.96 and 7436.37±518.67 ng/ml, respectively, which was observed at 1 h respectively. The mean peak plasma concentration of moxifloxacin following its intramuscular administration as single drug and in combination with tolfenamic acid were 243.52 ± 13.66 and 397.62 ± 41.55 ng/ml, observed at 2 and 0.67 h, respectively in male rats, where as m female rats mean values were 200.74 ±28.67 and 255.88 ± 30.89 ng/ml, observed at 2 and 1 h, respectively. Following intramuscular administration of tolfenamic acid (4 mg/kg) as single drug and in combination with moxifloxacin (5 mg/kg) in male wistar rats the mean values of half-life (t 1/2), volume of distribution (Vz), clearance (CI) and area under plasma drug concentration-time curve (AUC (0-∞)) of tolfenamic acid were 2.59 ±0.16 and 3.27 ± 0.32 hr, 822.17 ± 115.38 and 1249.64 ± 139.52 ml, 218.39 ± 25.47 and 265.18 ± 11.36 ml/hr and 20280.77 ± 3501.67 and 15229.18 ± 678.80 hr.ng/ml, respectively. Whereas in female rats mean values of tolfenamic acid were 2.78 ± 0.39 and 2.66 ± 0.53 hr, 756.42 ± 166.09 and 559.68 ±76.19 ml, 179.76 ± 20.01 and 152.75 ± 10.34 ml/hr and 23524.07 ± 2324.79 and 26830.41 ± 1914.84 hr.ng/ml, respectively. Volume of distribution (Vz) was significantly higher in male rats following concurrent intramuscular administration of tolfenamic acid and moxifloxacin. Following intramuscular administration of moxifloxacin alone in male rats, the mean volume of distribution, half-life (t1/2), area under the plasma drug concentration time curve from 0.0 hr to infinity (AUC (0-∞)) and total clearance (CI) were 12679.07 ± 1121.74 ml, 2.52 ± 0.23 h, 1483.21 ± 184.65 hr.ng/ml and 3605.99 ± 394.29 ml/hr, respectively. Following intramuscular administration of moxifloxacin in combination with tolfenamic acid in male rats significant decrease in elimination half-life (ti/2: 1.69 ± 0.21 h) and volume of distribution (Vz: 7856.51 ± 495.60 ml) has been observed compared to moxitloxacin treatment alone. Following intramuscular administration of moxifloxacin (5 mg/kg) as single drug and in combination with tolfenamic acid (4 mg/kg) in female wistar rats the mean values of half-life (t1/2), volume of distribution (Vz), clearance (CI) and area under plasma drug concentration-time curve (AUC (0-∞)) of moxifloxacin were 1.98 ± 0.38 and 1.44 ± 0.21 hr, 15005.77 ± 2939.77 and 12488.86 ± 1708.16 ml, 5360.93 ± 502.91 and 6163.69 ± 563.64 ml/hr and 975.84 ± 93.57 and 851.60 ± 90.61 hr.ng/ml. respectively. There were non significant difference (p<0.05) in pharmacokinetic parameters of moxifloxacin in female rats following concurrent intramuscular administration with tolfenamic acid as compared to moxifloxacin. Repeated intramuscular administration of tolfenamic acid (4 mg/kg) alone and in combination with moxifloxacin (5 mg/kg) repeated at 24 h interval for 14 days in male and female wistar rats were found safe based on evaluation of haematological (Hb, RBC, WBC, MCV, MCH, MCHC, HCT and DLC), blood biochemical (AST, ALT, ALP, total bilirubin, total serum protein, serum albumin, globulin, serum creatinine, urea, uric acid and blood glucose) parameters. Moreover, no gross or microscopic changes were found in the liver, kidney, heart, spleen, stomach, intestine and joint cartilages of male and female wistar rats. The present study revealed that administration of tolfenamic acid and moxifloxacin together altered pharmacokinetic profile of each other. Therefore, concomitant use of both the drugs requires therapeutic monitoring for potential pharmacokinetic drug interaction.
  • Thumbnail Image
    ThesisItemOpen Access
    STUDIES ON PHARMACOKINETICS, BIOAVAILABILITY AND SAFETY OF KETOPROFEN IN SHEEP
    (AAU, Anand, 2008) GONDALIYA, SANJAY RAMESHBHAI; BHAVSAR, S. K.
    Levofloxacin is the active L - isomer of the racemate ofloxacin, a fluorinated quinolone has broad-spectrum activity and good antiKetoprofen is a non steroidal anti-inflammatory drug (NSAID) used for its antiinflammatory, analgesic and antipyretic properties in Veterinary medicine. The pharmacokinetics of ketoprofen after its single dose intravenous and intramuscular administration was investigated in six patanwadi breed of sheep by non compartmental approach. The drug was administered at the dose rate of 3.0 mg.kg-1 body weight and assayed in plasma by HPLC analysis. The present study also evaluated safety of ketoprofen (3.0 mg.kg-1) after repeated administration at 24 h interval for 5 days in sheep. Following intravenous and intramuscular administration of ketoprofen, values of elimination half-life (t1/2β), volume of distribution of drug at steady state [Vd(ss)], total body clearance (CIB), area under plasma drug concentration-time curve (AUC), and mean residence time (MRT) were 1.66 ± 0.12 and 3.31 ± 0.16 h; 0.31 ± 0.01 and 0.83 ± 0.08 L.kg-1; 5.53 ± 0.27 and 3.85 ± 0.30 ml.min-1.kg-1; 9.32 ± 0.32 and 13.58 ± 0.91 ng.h.ml-1 and 1.00 ± 0.06 and 3.67 ± 0.41 h, respectively. Following intramuscular administrationacterial activity at low plasma/tissue concentration. The present study was designed to investigate pharmacokinetics of levofloxacin following single dose intravenous and oral administration at the dose rate of 10 mg/kg of body weight and to evaluate safety after repeated administration (10 mg/kg) of levofloxacin at 12 hours interval for 14 days in layer birds. Drug concentration in serum was determined using High Performance Liquid Chromatography (HPLC). Following intravenous administration, the serum drug concentration-time curves were analyzed by non-compartmental approach. Following intravenous administration the therapeutically effective serum concentration of levofloxacm > 0.13 µg/ml was maintamed for up to 12 hours. Based on the serum drug concentrations, various pharmacokinetic parameters like elimination half-life (t1/2β) (3.08 ± 0.05 hours), apparent volume of distribution (Vd(area)) (4.02 ± 0.079 1/kg), volume of distribution of drug at steady-state (Vd(ss)) (3.23 ± 0.055 1/kg), total body clearance (CIB) (15.09 ± 0.21 ml/min/kg), area under serum drug concentration-time curve (AUG) (11.07 ± 0.14 µg.h/ml), area under first moment of curve (AUMC) (39.56 ± 0.89 µg.h2/ml) and mean residence time (MRT) (3.57 ± 0.052 hours) were determined. peak plasma concentration (Cmax) of 4.91 ± 0.52 was achieved at 0.5 h (tmax)- Bioavailability of the drug was 73.16 ± 5.58. Longer elimination half-life, larger volume of distribution at steady state and slower total body clearance of ketoprofen following intramuscular administration as compared to intravenous administration makes it more suitable for intramuscular use in sheep. Repeated intravenous administration of ketoprofen (3.0 mg.kg-1 body weight repeated at 24 h interval for 5 days) in sheep was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC) and blood biochemical (AKP, ACP, AST, ALT, LDH, Total Bilirubin, Serum Creatinine, Total Serum Protein, Serum Albumin and Blood glucose) parameters except BUN. It is advisable to monitor kidney functions during long term therapy with ketoprofen in sheep. The present study indicate that intramuscular administration of ketoprofen at dose rate of 3.0 mg.kg'-1 in sheep would be provide a satisfactory plasma concentration of drug equal to its median effective concentration up to 18 h. Therefore, ketoprofen given via intramuscular route at the dose rate of 3.0 mg.kg-1 of body weight repeated every 18 h would be satisfactory therapeutic dosage regimen for sheep. However, therapeutic efficacy of the dosage remains to be evaluated in clinical cases under field conditions.
  • Thumbnail Image
    ThesisItemOpen Access
    STUDIES ON THE PHARMACOKINETICS OF CEFEPIME IN SURTI GOATS
    (AAU, Anand, 2005) PATANI, KALPESH ZINABHAI; Sarvaiya, J. G.
    Cefepime, a fourth-generation semi-synthetic broad spectrum cephalosporin has bactericidal action against broad range of bacteria including those that are resistant to conventional antibacterial drugs. The present study was designed to investigate pharmacokinetics of cefepime in Surti goats following single dose intravenous and intramuscular administration at the dose rate of 10 mg kg-1 of body weight. Drug concentration in serum was determined using High Performance Liquid Chromatography (HPLC). Following intravenous and intramuscular administration, the serum concentration-time curves were characteristic of a two compartment open model. Following intravenous administration the mean serum cefepime level of 77.81 ± 5.51 µg ml-1 was observed at 0.033 h (2 minutes). The therapeutically effective concentration of cefepime (> 1.00 µg ml-1) was maintained in serum up to 8 h. The distribution half-life (t1/2aα) and elimination half-life (t1/2β) were 0.20 ± 0.02 h and 2.71 ± 0.08 h, respectively. The mean values of apparent volume of distribution [Vd(area)] and volume of distribution of drug at steady-state (Vdss) were calculated to be 0.52 ± 0.04 and 0.35 ± 0.03 L kg-1, respectively. The mean value of total body clearance (CIB) was 2.19 ± 0.15 ml min-1 kg-1. The average values for area under serum drug concentration-time curve (AUC) and area under first moment of curve (AUMC) were 78.38 ± 7.05 )µg h ml-1 and 203.8 ± 10.05 µg h2ml-1. The average value of mean residence time (MRT) was 2.64 ± 0.09 h.
  • Thumbnail Image
    ThesisItemOpen Access
    STUDY OF EFFICACY AND TOXICITY OF ROSUVASTATIN IN NORMAL AND HIGH FAT-HIGH CHOLESTEROL DIET FED HAMSTERS
    (AAU, Anand, 2009) GOTHI, ANIL KALIDAS; Thaker, A. M.
    Rosuvastatin, a new statin is indicated for the treatment of dyslipidemia. The present study was conducted to evaluate the efficacy and toxicity of rosuvastatin in normal and high fat-high cholesterol diet fed (dyslipidemic) hamsters. The study was conducted on 86 male Golden Syrian hamsters. The animals were administered with rosuvastatin at 1, 10, 25, 50 and 100 mg/kg doses in normal diet fed hamsters and at 0.1, 0.3, 0.5, 1 and 1.5 mg/kg doses in high fat high cholesterol diet fed hamsters. The animals were observed throughout the experimental period for any toxic manifestation and daily body weight was recorded to see the effect. At 0, 7th and 14th days of treatment, animals were subjected to blood collection and serum sample were analyzed for different biochemical parameters. At the end of treatment period animals were sacrificed and necropsy was performed, and tissues were collected (heart, liver, kidney and muscle) for histopathological studies. Dyslipidemic animal model was developed after feeding of high fat high cholesterol diet for 14 days. In this dyslipidemic animal model serum concentration of triglyceride, total cholesterol and low density lipoprotein cholesterol level increased by 2.5, 3, and 4 fold as compared to normal diet fed hamsters. Body weight was significantly decreased at 100 mg/kg dose in normal hamsters and, at 1 and 1.5 mg/kg dose in dyslipidemic hamsters. Rosuvastatin produced significant hypotriglyceridemia at 50 and 100 mg/kg dose in normal hamsters and, at 0.3, 0.5, 1.0 and 1.5 mg/kg dose in dyslipidemic hamsters. Rosuvastatin at 100 mg/kg dose produced significant hypocholesterolemia in normal hamsters while, at 0.1, 0.3, 0.5, 1.0 and 1.5 mg/kg dose there was no reduction in total cholesterol. Rosuvastatin produced good efficacy means significant reduction in low density lipoprotein cholesterol at 50 and 100 mg/kg doses in normal hamsters, while at 1.0 and 1.5 mg/kg doses in dyslipidemic hamsters. High density lipoprotein cholesterol level significantly decreased in normal hamsters at 100 mg/kg dose, while in dyslipidemic hamsters it was significantly increased at 1.0 and 1.5 mg/kg doses. Low density lipoprotein to high density lipoprotein cholesterol ratio was significantly reduced at 100 mg/kg dose in normal hamsters, and at 1 and 1.5 mg/kg dose in dyslipidemic hamsters. Aspartate aminotransferase and alanine aminotransferase level were significantly increased at 50 and 100 mg/kg dose in normal hamsters while, at 0.5,1.0 and 1.5 mg/kg dose in dyslipidemic hamsters. Alkaline phosphatase and total bilirubin levels were significantly increased at 100 mg/kg dose in normal hamsters while at 1 and 1.5 mg/kg dose in dyslipidemic hamsters. It was clearly indicated that liver toxicity of rosuvastatin was higher in dyslipidemic animal model. There was no significant treatment related changes in Serum creatine kinase level in both normal and dyslipidemic hamsters. Liver weight was significantly increased at doses of 50 and 100 mg/kg in normal hamsters whereas; it was decreased at 0.3, 0.5, 1 and 1.5 mg/kg doses in dyslipidemic hamsters. Kidney weight was significantly increased at 100 mg/kg dose in normal hamsters and, at 0.3, 0.5, 1 and 1.5 mg/kg doses in dyslipidemic hamsters. Gross postmortem changes, observed in high dose group (50 and 100 mg/kg) of rosuvastatin were mottled liver in normal hamsters. In high fat high cholesterol diet fed hamsters all treatment groups along with control group, all animals showed pale and mottled liver. In dyslipidemic hamsters rosuvastatin at 1.0 and 1.5 mg/kg dose showed dark red colour kidney and marked muscle wasting condition. Microscopic changes observed in liver were necrosis of hepatocyte, mononuclear cells infiltration and cytoplasmic vacuolization at 25, 50 and 100 mg/kg doses in normal hamsters, while inflammatory cell infiltration, fatty changes, bile duct proliferation and hepatic necrosis was observed at 0.5, 1 and 1.5 mg/kg doses in dyslipidemic hamsters. Skeletal muscles showed segmental muscle fiber degeneration in 50 and 100 mg/kg dose groups of normal hamsters and 1 and 1.5 mg/kg dose groups of dyslipidemic hamsters. Heart showed myocardial degeneration and necrosis at 25, 50 and 100 mg/kg dose in normal hamsters and, at 0.5, 1 and 1.5 mg/kg dose in dyslipidemic hamsters. Kidney showed renal tubular degeneration in normal hamsters at 25, 50 and 100 mg/kg dose and, at 1 and 1.5 mg/kg dose in dyslipidemic hamsters. In the present study in dyslipidemic hamsters, rosuvastatin, at administered doses, has been found more toxic as compared to normal hamsters.
  • Thumbnail Image
    ThesisItemOpen Access
    TOXICOLOGICAL AND IMMUNOLOGICAL STUDIES ON SHORT TERM EXPOSURE OF ALPHACYPERMETHRIN IN WHITE LEGHORN COCKERELS
    (AAU, Anand, 2006) PANDEY, NAVNEET KUMAR; Sarvaiya, J. G.
    The present study was conducted on Day old White Leghorn cockerels; approximate median lethal dose (ALD50) of Alphacypermethrin used for the study was 562.5 mg/kg. One hundred twenty five birds were divided into five different groups. The birds of group C1 were given no treatment and served as control. Group C2 was administered corn oil (Iml/kg) and served as control (vehicle). Group T1 was given 1/40th of ALD50 (14.0625 mg/kg), and Group T2 was put on 1/30th of ALD50 (18.725 mg/kg), while group T3 received 1/20th of ALD50 (28.125 mg/kg) of Alphacypermethrin suspended in 1 ml of com oil. Once daily oral dosing was carried out for 28 days. All the birds were monitored for any observable toxic symptoms throughout the experimental period and they were also weighed weekly to monitor body weight gain. The blood samples were collected directly from heart before sacrifice on day 14 and day 28 of the study and were analyzed for hematological, biochemical and immunological parameters. Birds were sacrificed twice on day 14 and 28 of the experiment, organs (liver, spleen, thymus and bursa) weights were measured and organs (lung, liver, spleen, thymus, kidney, and bursa) were collected for histopathological examinations. Severity and extent of the clinical signs varied according to dose administered to the birds. The clinical symptoms observed were sudden onset of depression, salivation, reduced feed intake and green diarrhea. 2-3 birds died during the study period. There was a reduction in the body weight gain of the insecticide treated birds. No alteration was recorded in haematological parameters (hemoglobin, packed cell volume, total erythrocyte count and total leukocyte count) due to Alphacypermethrin exposure. Dose dependent significant increase in blood glucose due to administration of Alphacypermethrin was observed. A significant dose dependent increase in Serum Glutamic Oxaloacetate Transaminase, Serum Glutamic Pyruvate Transaminase, Alkaline Phosphatase, Lactate Dehydrogenase and Creatinine level of the birds treated with the insecticide indicated systemic toxicity. A significant decrease in serum proteins was recorded on both, day 14 and 28, of experiment. A significant decrease in serum albumin and globulin was observed on 28th day of study. Dose dependent decrease in organ weight was observed on day 28 of study. During the experimentation, Alphacypermethrin had immunosuppressive effect on humoral immune response in treatment groups in dose dependent manner on both day 14 and 28 of experimentation. Present study revealed that though Alphacypermethrin is moderately toxic to the birds; it seems to be toxic for multiple systems including immune system in growing birds at given doses. Gross postmortem and histopathological changes in various organs of birds treated with Alphacypermethrin were observed with typical pyrethroid dose dependent toxicity signs. Microscopic changes observed in different organs viz. liver, lung, kidney spleen, thymus and bursa which were typical to insecticide poisoning. Though Alphacypermethrin has been reported mild to moderately toxic to the birds. doses of Alphacypermethrin given in the present study produced mild toxicity to multiple body systems of growing birds including immune system.