No abstract

Metronidazole is antimicrobial drug for human and animal use, The more characteristic side effect associated with use high dose of metronidazole is neurotoxic signs, some of these signs that recorded in animal represented by ataxia and tremor, there is limited information is available on the pharmacological profile of metronidazole in birds The aim of our study explain some of its neurological effect in chicks by its interaction with one of organophosphorus insecticide chlorpyrifos that have well-known excitatory effect on nervous system. Median Lethal Doses (LD50) of metronidazole and chlorpyrifos were determined depending on up and down method. The intraperitoneal and oral LD50 of metronidazole were 516.9 mg/kg, 3061.8 mg/kg respectively. The oral LD50 of chlorpyrifos was 13.705 mg/kg, intraperitoneal treatment of metronidazole with Oral treatment of chlorpyrifos in ratio 1:1, 1: 0.5, and 0.5:1, respectively of LD50 at the same time increased LD50 for metronidazole and chlorpyrifos and the isobolographic analysis showed that the points of interaction occurred above the diagonal line connecting between LD50 of each; while oral treatment of metronidazole and chlorpyrifos in ratio 1:0.5 LD50 at the same time decreased LD50 for metronidazole and chlorpyrifos and the point of interaction was above the diagonal line connecting between LD50 of each in conclusion we found that isobolografhic analysis for metronidazole and chlorpyrifos in different percentages and routs of treatment reveal to antagonist effect despite the similarity in the toxic signs.

Ciprofloxacin (CFX) and ketoprofen (KPN) are used widely in combination in veterinary interventions for bacterial infections, so in this study the effect of KPN was studied on the efficacy of CFX, by measuring its plasma concentration and pharmacokinetic parameters in 7-10 day-old chickens. The analgesic median effective dose (ED50) of KPN was determined to be 1.62 mg/kg, IM, in the chickens. The preferable analgesic dose of KPN to be used with CFX was 4 mg/kg, IM, which differs significantly from KPN 2 mg/kg, IM,. The CFX plasma concentrations alone (8 mg/kg, IM) measured at different times (0.5, 1, 2, 4 and 24 hours) were 3.31, 3.60, 3.21, 2.70 and 0.17 μg/mL while its concentration was elevated by 53, 54, 90, 107 and 418 % when coadministered with KPN (4 mg/kg, IM) to 5.05, 5.53, 6.10, 5.59 and 0.88 μg/mL in the chickens, respectively. CFX pharmacokinetic parameters, such as the area under the curve (AUC), the area under the moment curve (AUMC), mean residence time (MRT), half-life (t1/2β), Tmax, and Cmax increased when KPN was coadministered with CFX by 129, 289, 70, 49, 100 and 69 %, whereas the elimination rate constant (Kel), the volume of distribution at steady state (Vss) and clearance (Cl) decreased by 36, 34 and 58 %, respectively. It was concluded that coadministration of KPN alters the plasma concentration and the pharmacokinetic parameters of CFX, suggesting that the CFX dose can be reduced when used with KPN to achieve the desired concentration of CFX in the plasma, as an antibacterial for treatment of infected animals.

Despite the widespread use of xylazine in veterinary medicine, studies on its neurotoxicity are limited. So, our current study aims to reveal its neurotoxicity in chicks by determining the (LD50) of xylazine in Dixon's procedure. Moreover, it aims to study the effects of a small and repeated dose of xylazine on neurobehavioral test and the toxic doses of xylazine on the concentration of (glycine and glutamate) in the plasma of chicks and on the brain tissue after 60 and 90 minutes of injection. The LD50 of xylazine by injection into the chest muscle was 26.65 mg/kg. The injection of xylazine at a dose of 3 and 6 mg/kg in the chest muscle for three consecutive days caused an inhibition in motor activity within the open field as well as a significant elevation in the tonic immobility test response, injection of xylazine at doses 48.96 mg/kg ,60 and 90 minutes after the injection led to a significant increase in the glycine concentration as well as a significant decrease in glutamate after 90 minutes in the plasma of chicks, accompanied by histological variation in the brain tissue characterized by necrosis of neurons, vasogenic edema, neurophagia, cavities, infarction, necrosis of Purkinjean cell with decrees in the number of it. Our results revealed that xylazine had neurotoxic effects in chicks, represented by inhibition of neural behavior and motor activity within the open field, accompanied by a change in the concentration of glycine and glutamate in the plasma of chicks and histological variation in the brain tissue of chicks.