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Lala Lajpat Rai University of Veterinary & Animal Sciences, Hisar
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ThesisItem Restricted Pharmacokinetic and toxicity studies of ofloxacin in poultry(LUVAS, 2006) Anil Kumar; Jain, S.K.Ofloxacin, a new second generation fluorinated quinolone, possesses broad antimicrobial spectrum against gram-positive and gram-negative pathogens including obligate anaerobes. These excellent antimicrobial characteristics of ofloxacin indicate its high potential in treating common infections such as mycoplasmosis, colibacillosis, pasteurollosis etc. in chicken. For successful therapeutic application, the pharmacokinetic and toxicity studies of ofloxacin were conducted in adult female WLH chicken Ofloxacin concentrations in plasma were determined using a high performance liquid chromatography (HPLC) assay. Various pharmacokinetic parameters were computed by using a non linear iterative curve fitting computer program ‘PHARMKIT’. The disposition of ofloxacin followed two-compartment open model following single i.v. administration (10 mg.kg-1b.wt.) with rapid distribution. The distribution rate constant (), elimination rate constant (), distribution half-life (t1/2) and elimination half-life (t½) values were 8.21 h-1, 0.34 h-1, 0.09 h and 2.09 h, respectively. The values of k12, k21, kel and ClB were found to be 3.35 h-1, 4.16 h-1, 0.61 h-1 and 0.18 L.kg-1.h-1, respectively. The values of AUC, MRT, Vz(area) and tcp(ther) were 63.61 g.ml-1.h, 2.93 h, 0.51 L.kg-1 and 14.09 h, respectively. The disposition kinetics of ofloxacin was adequately described by one-compartment open model after absorption phase following single oral administration (10 mg.kg-1). Ofloxacin was rapidly absorbed and the maximum concentration of Ofloxacin was observed to be 3.40 g.ml-1 1 h t(max). The values of ka, t½ka, and t½ were determined to be 2.69 h-1, 0.27 h, 0.29 h-1 and 2.47 h, respectively. The calculated values of Vz(area), Cl, MRT and tcp(ther) were 0.89 L.kg-1, 0.25 L.kg-1.h-1, 4.43 h and 14.68 h, respectively. Considering MIC as 0.5 g.ml-1, the loading and maintenance doses of ofloxacin were computed to be 1.95 and 0.70 mg.kg-1, respectively at a dosage interval of 6 hours following i.v. route. The values of loading and maintenance doses of ofloxacin following oral administration were determined to be 2.45 and 0.90 mg.kg-1 at the same dosage interval of 6 h in adult WLH chicken. In acute toxicity study, no significant effect was observed on various haematological parameters viz. Hb, PCV, TEC at 6, 24 and 72 h following single oral administration of ofloxacin at a dose rate of 20 mg.kg-1 b.wt. in adult WLH chicken. Ofloxacin caused significant decrease in total protein and albumin, but significant increase in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 24 h. There was no significant effect on creatinine. Mild histopathological lesions were also observed in liver and kidney at 24 h. However, this effect was found to be reversible and all biochemical and histopathological changes became normal at 72 h. In subacute toxicity study, ofloxacin did not cause any significant effect on haematological parameters viz. Hb, PCV, TEC on 7, 14 and 21days following daily oral administration at a dose of 10 mg.kg-1 b. wt for 14 days. Ofloxacin caused significant decrease in total protein and albumin content. A significant increase in the levels of AST and ALT was observed on 14th day. Ofloxacin did not cause any significant effect on creatinine. Mild to moderate histopathological lesions were observed in liver and kidney on 14th day. However, all the biochemical and histopathological changes became normal on 21st day in adult female WLH chicken.ThesisItem Restricted Age and gender related neuropsychobehavioural toxicodynamics of imidacloprid in rats(LUVAS, 2009) Bachanti, Deepak Ramrao; Punia, J.S.Acute toxicity study of imidacloprid and its effects on neuropsychobehavioural profiles were studied in adult, prepubertal and weanling male and female Wistar rats to find out the differences in age and gender related toxicodynamics. The oral MTD value of imidacloprid was 1900 mg/kg in adult male rats, 1800 mg/kg in adult female rats, 1700 mg/kg in prepubertal male rats, 1600 mg/kg in prepubertal female rats and 1500 mg/kg in both weanling male and female rats. Thus MTD of imidacloprid varied with age and gender, the young one and female were found to be more sensitive. This indicated the relation of toxicity/sensitivity is sex hormone dependent, the female being more sensitive. Significant difference in onset, peak time and intensity of neurobehavioural effects were found in weanling, prepubertal and adult rats in most of the behavioural parameters with respect to age and gender. No autonomic muscarinic effect was observed in any of the groups during acute toxicity and neurobehavioural studies at any of the dose levels of imidacloprid used in this investigation indicating that even at lethal dose the selectivity profile of imidacloprid for nicotinic acetylcholine receptor will be same. Pain response and touch response were reduced in weanling, prepubertal and adult rats. Prepubertal and weanling rats were similarly affected. Corneal reflex was affected in weanling, prepubertal and adult rats whereas pinnal reflex and startle response was not affected in adult rats. Spontaneous motor activity (SMA) was reduced more in weanling maleS as compared to prepubertal and adult male rats. Overall, weanling rats were more sensitive to toxicity of imidacloprid and prepubertal and adult female were more affected than corresponding male rats.ThesisItem Restricted Neuropsychobehavioural toxicodynamics of imidacloprid–a nitroguanidine insecticide(LUVAS, 2005) Sharma, Rajeev; Punia, J.S.The present investigation was designed to study the neuropsychobehavioural toxicodynamics of imidacloprid, a nitroguanidine insecticide, in adult swiss albino male mice and wistar rats. Following intraperitoneal administration of imidacloprid in mice, the main gross observable symptoms were decreased alertness, decreased grooming, restlessness, tremors, respiratory distress, abnormal body posture, open mouth breathing and flexion of head. No muscarinic effects were observed. The maximal tolerated dose of imiodacloprid was 55 mg/kg, i.p. Imidacloprid decreased spontaneous motor activity in a dose dependent manner and induced motor incoordination. It antagonized cocaine and amphetamine induced behaviour. Imidacloprid potentiated the seizures induced by electroshock, pentylenetetrazole, strychnine, tremorine and picrotoxin to tonic convulsions or death. It decreased the severity of lithium pilocarpine induced status epilepticus but increased the severity of status epilepticus induced by phenytoin pentylenetetrazole to tonic convulsions. Imidacloprid prolonged the barbiturates induced hypnosis. Prior administration of diazepam and carbamazepine decreased the tremors and prior administration of phenytoin reduced the restlessness induced by imidacloprid. However, prior treatment with fluoxetin had no effect on imidacloprid induced characteristic behavioural symptoms. Imidacloprid did not behave exactly like nicotine. It possess no autonomic muscarinic action. Effect of imidacloprid indicated the possibility of involvement of dopaminergic system and direct excitatory action at neuromuscular junction.ThesisItem Restricted Pharmacological and Toxicological Studies of Spinosad- A Bioinsecticide(LUVAS, 2009) Sonu Devi; Rana, R.D.In the present investigation, pharmacological and toxicological studies of spinosad formulation (spintor, 45% sc) were conducted in Swiss albino mice and Wistar albino rats. The calculated oral maximum tolerated doses of spinosad were 3700 mg/kg body weight in mice and 2500 mg / kg body weight in rats. Main grossly observable toxic symptoms were depression, weakness, respiratory distress, rough hair coat, piloerection, hypractivity and perineal ventral soiling. Spinosad treated mice and rats showed significnat decrease in body weight gain. Spinosad caused slight decrease in HB, TLC, TEC, lymphocyte counts but slight increase in neutrophil counts. Spinosad treated mice showed significant decrease in spontaneous motor activity and also amphetamine induced increased locomotor activity at dose levels of 740 and 1480 mg/kg Foreced lacomotor activity was intact in mice. Spinosad did not produce any analgesic and convulsant activity in mice. It did not cause any tranquillizing activity in rats at dose levels of 500 and 1000 mg/kg. Rats subjected to subacute (14 days) and subchronic (28 days) toxicity studies of spinosad (62.5 and 125 mg/kg) did not show any iicharacteristic toxic symptom. There was decresae in body weight gain. Slight decrease in Hb content, TEC, TLC, neutrophil counts but slight increase in lymphocyte counts were observed. Spinosad produced slight increase in relative weights of liver, kidney and epididymides. Spinosad caused slight decrease in total plasma protein albumin, and globulin concentrations. It produced slight incresae in plasma cholesterol, urea nitrogen concentrations, ALT and AST levels. The studies indicated that spinosad caused only mild low degree adverse effects in adult male mice and rats.ThesisItem Restricted Pharmacological and toxicological studies of indoxacarb - an oxadiazine insecticide(LUVAS, 2008) Shit, Shiba Prasad; Panghal, R. S.The oral maximum tolerated dose (MTD) of indoxacarb formulation (Kingdoxa) after was 500 and 600 mg/kg in mice and rats, respectively. The major gross observable symptoms induced by indoxacarb in mice and rats were motor incoordination, vigorous rolling, salivation, restlessness, head tilt, intermittent clonic convulsions, depression, open mouth breathing and death. Indoxacarb treated rats and mice showed decrease in body weight gain and decrease in haemoglobin content, leukocyte counts and erythrocyte counts, which indicated that it has adverse effects on erythropoietic system. Indoxacarb decreased spontaneous motor activity (SMA) and force locomotor activity (FLA) in mice at both the dose levels (100 and 200 mg/kg) in mice. The effect of amphetamine induced increased locomotor activity was antagonized by indoxacarb in mice. The compound produces no analgesic and tranquillizing activity in mice and rats respectively. Indoxacarb produced some protection against supramaximal electroshock induced seizures and potentiated metrazole induced convulsions and strychnine induced convulsions in mice. The body weight gain was not affected significantly in rats in 14 and 28 days studies at the dose levels of 12 and 24 mg/kg. Indoxacarb was found to decrease in haemoglobin concentration, erythrocyte counts and leukocyte counts significantly at both the dose levels in 28 days study. Slight congested lungs and liver and increased spleen size were observed. The plasma glucose level was increased nonsignificantly at higher dose level. There was significant increase in plasma creatinine level at higher dose in 28 days study. Indoxacarb did not produce any effect on plasma GOT but caused significant increase in plasma GPT levels in rats at both the dose levels in 28 days study. These studies indicated that indoxacarb was moderately toxic to the adult male rats and mice.ThesisItem Restricted Pharmacological and toxicological studies of thiamethoxam - A neonicotinoid insecticide(LUVAS, 2008) Sole, Sushant Shivdas; Vinod KumarThiamethoxam is compound belonging to newer class of insecticide called neonicotinoids and used primarily as plant systemic. The oral maximum tolerated dose (MTD) of thiamethoxam formulation (Actara) was 1600 and 4200 mg/kg in mice and rats, respectively. The major gross observable symptoms induced by thiamethoxam in mice were ataxia, straub tail, tremors, convulsions on touch and sound, change in body posture with tilted head, decreased grip strength and decreased spontaneous motor activity. Symptoms were not much prominent in rats and symptoms observed were slight tremors on touch and intermittent clonic convulsions before death. No delayed toxic effect was observed on keeping them up to 14 days following single administration of thiamethoxam at MTD through oral route. These groups of rats and mice showed decrease in Hb content, increase in total leukocyte and change in differential leukocyte pattern. The body weights of treated group of rats were decreased as compared to control animals. Thiamethoxam showed dose dependent decreas in SMA and FLA in mice at 320 and 640 mg/kg dose levels. The effect of amphetamine induced increased locomotor activity was antagonized by thiamethoxam in mice. The compound has no analgesic activity in mice and tranquilizing activity in rats. Thiamethoxam potentiated the supramaximal and strychnine induced convulsions, which indicated convulsant effect of thiamethoxam in mice but no change was observed in pattern of metrazole induced convulsions. The subacute and subchronic toxicity study in rats did not show any characteristic gross observable toxic symptoms throughout the study at either (420 or 840 mg/kg) dose levels. Thiamethoxam produced decreasing trend in body weight gain in animals of subchronic toxicity study. The compound was found to decrease Hb content and total erythrocyte count and change in differential leukocyte pattern. No significant change relative organ weight of animals was observed except significant increase in testes and epididymis weight. Thiamethoxam caused increase in creatinine level and decrease in plasma triglyceride levels at both the dose levels (420 or 840 mg/kg) in subacute and subchronic toxicity study. The BUN was increased at both the dose levels during subchronic toxicity study. In subchronic toxicity study, histopathological studies revealed prominent changes in kidney, liver and spleen. Various cellular lesions observed in liver were vacuolation in cell cytoplasm (more pronounced at the periphery of the vacuole), distended sinusoidal space and cloudy swelling. In case of kidney, the lesions were focal haemorrhages, mild tubular degeneration, vacuolation of cell cytoplasm and in some cases contracted Bowman’s capsule and glomeruli. Diffused extensive haemorrhages and depletion of lymphocytes were observed in spleen. Lesions of less severity were observed in liver, kidney and spleen in subacute toxicity studies.